75 results on '"Luo, R"'
Search Results
2. HST viewing of spectacular star-forming trails behind ESO 137-001
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William Waldron, Ming Sun, Rongxin Luo, Sunil Laudari, Marios Chatzikos, Suresh Sivanandam, Jeffrey D P Kenney, Pavel Jáchym, G Mark Voit, Megan Donahue, Matteo Fossati, Waldron, W, Sun, M, Luo, R, Laudari, S, Chatzikos, M, Sivanandam, S, Kenney, J, Jachym, P, Voit, G, Donahue, M, and Fossati, M
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High Energy Astrophysical Phenomena (astro-ph.HE) ,Space and Planetary Science ,Astrophysics of Galaxies (astro-ph.GA) ,galaxies: clusters: individual: Abell 3627 ,galaxies: star formation ,FOS: Physical sciences ,Astronomy and Astrophysics ,galaxies: starburst ,Astrophysics - High Energy Astrophysical Phenomena ,galaxies: evolution ,galaxies: individual: (ESO 137-001) ,Astrophysics - Astrophysics of Galaxies - Abstract
We present the results from the HST WFC3 and ACS data on an archetypal galaxy undergoing ram pressure stripping (RPS), ESO 137-001, in the nearby cluster Abell 3627. ESO 137-001 is known to host a prominent stripped tail detected in many bands from X-rays, Halpha to CO. The HST data reveal significant features indicative of RPS such as asymmetric dust distribution and surface brightness as well as many blue young star complexes in the tail. We study the correlation between the blue young star complexes from HST, HII regions from Halpha (MUSE) and dense molecular clouds from CO (ALMA). The correlation between the HST blue star clusters and the HII regions is very good, while their correlation with the dense CO clumps are typically not good, presumably due in part to evolutionary effects. In comparison to the Starburst99+Cloudy model, many blue regions are found to be young (< 10 Myr) and the total star formation (SF) rate in the tail is 0.3 - 0.6 M_Sun/yr for sources measured with ages less than 100 Myr, about 40% of the SF rate in the galaxy. We trace SF over at least 100 Myr and give a full picture of the recent SF history in the tail. We also demonstrate the importance of including nebular emissions and a nebular to stellar extinction correction factor when comparing the model to the broadband data. Our work on ESO 137-001 demonstrates the importance of HST data for constraining the SF history in stripped tails., 22 pages, 20 figures, 4 tables, published in MNRAS 06/2023
- Published
- 2023
3. An H α/X-ray orphan cloud as a signpost of intracluster medium clumping
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Yutaka Komiyama, Chong Ge, Craig L. Sarazin, Paul Nulsen, Rongxin Luo, Giuseppe Gavazzi, Massimo Gaspari, Jin Koda, Ming Sun, Masafumi Yagi, Matteo Fossati, Tim Edge, P. Jáchym, Michitoshi Yoshida, Alessandro Boselli, Ge, C, Luo, R, Sun, M, Yagi, M, Jachym, P, Boselli, A, Fossati, M, Nulsen, P, Sarazin, C, Edge, T, Gavazzi, G, Gaspari, M, Koda, J, Komiyama, Y, Yoshida, M, Laboratoire d'Astrophysique de Marseille (LAM), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Centre National d'Études Spatiales [Toulouse] (CNES)
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Astrophysics::High Energy Astrophysical Phenomena ,Galaxies: clusters: individual: Abell 1367 ,Astrophysics::Cosmology and Extragalactic Astrophysics ,Astrophysics ,01 natural sciences ,Luminosity ,Intracluster medium ,0103 physical sciences ,Emission spectrum ,010303 astronomy & astrophysics ,Astrophysics::Galaxy Astrophysics ,Physics ,Effective radius ,[SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph] ,010308 nuclear & particles physics ,Star formation ,Velocity dispersion ,Astronomy and Astrophysics ,X-rays: galaxies: cluster ,Galaxy ,Interstellar medium ,Galaxies: ISM ,[SDU]Sciences of the Universe [physics] ,Space and Planetary Science ,X-rays: galaxies: clusters ,[PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph] ,Galaxies: clusters: intracluster medium - Abstract
16 pages, 9 figures, 2 tables, MNRAS, in press, minor changes with abstract/conclusion the same; International audience; ABSTRACT Recent studies have highlighted the potential significance of intracluster medium (ICM) clumping and its important implications for cluster cosmology and baryon physics. Many of the ICM clumps can originate from infalling galaxies, as stripped interstellar medium (ISM) mixing into the hot ICM. However, a direct connection between ICM clumping and stripped ISM has not been unambiguously established before. Here, we present the discovery of the first and still the only known isolated cloud (or orphan cloud [OC]) detected in both X-rays and H α in the nearby cluster A1367. With an effective radius of 30 kpc, this cloud has an average X-ray temperature of 1.6 keV, a bolometric X-ray luminosity of ∼3.1 × 1041 erg s−1, and a hot gas mass of ∼1010 M⊙. From the Multi-Unit Spectroscopic Explorer (MUSE) data, the OC shows an interesting velocity gradient nearly along the east-west direction with a low level of velocity dispersion of ∼80 km s−1, which may suggest a low level of the ICM turbulence. The emission line diagnostics suggest little star formation in the main H α cloud and a low-ionization (nuclear) emission-line regions like spectrum, but the excitation mechanisms remain unclear. This example shows that stripped ISM, even long after the initial removal from the galaxy, can still induce ICM inhomogeneities. We suggest that the magnetic field can stabilize the OC by suppressing hydrodynamic instabilities and thermal conduction. This example also suggests that at least some ICM clumps are multiphase in nature and implies that the ICM clumps can also be traced in H α. Thus, future deep and wide-field H α surveys can be used to probe the ICM clumping and turbulence.
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- 2021
4. Unveiling promising drug targets for autism spectrum disorder: insights from genetics, transcriptomics, and proteomics.
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Jiang R, Huang W, Qiu X, Chen J, Luo R, Zeng R, Tong S, Lyu Y, Sun P, Lian Q, Leung FW, Liu Y, Sha W, and Chen H
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- Humans, Animals, Mice, Transcriptome, Quantitative Trait Loci, Protein Interaction Maps drug effects, Mice, Knockout, Molecular Targeted Therapy, Autism Spectrum Disorder drug therapy, Autism Spectrum Disorder genetics, Autism Spectrum Disorder metabolism, Proteomics, Genome-Wide Association Study
- Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which current treatments are limited and drug development costs are prohibitive. Identifying drug targets for ASD is crucial for the development of targeted therapies. Summary-level data of expression quantitative trait loci obtained from GTEx, protein quantitative trait loci data from the ROSMAP project, and two ASD genome-wide association studies datasets were utilized for discovery and replication. We conducted a combined analysis using Mendelian randomization (MR), transcriptome-wide association studies, Bayesian colocalization, and summary-data-based MR to identify potential therapeutic targets associated with ASD and examine whether there are shared causal variants among them. Furthermore, pathway and drug enrichment analyses were performed to further explore the underlying mechanisms and summarize the current status of pharmacological targets for developing drugs to treat ASD. The protein-protein interaction (PPI) network and mouse knockout models were performed to estimate the effect of therapeutic targets. A total of 17 genes revealed causal associations with ASD and were identified as potential targets for ASD patients. Cathepsin B (CTSB) [odd ratio (OR) = 2.66 95, confidence interval (CI): 1.28-5.52, P = 8.84 × 10-3], gamma-aminobutyric acid type B receptor subunit 1 (GABBR1) (OR = 1.99, 95CI: 1.06-3.75, P = 3.24 × 10-2), and formin like 1 (FMNL1) (OR = 0.15, 95CI: 0.04-0.58, P = 5.59 × 10-3) were replicated in the proteome-wide MR analyses. In Drugbank, two potential therapeutic drugs, Acamprosate (GABBR1 inhibitor) and Bryostatin 1 (CASP8 inhibitor), were inferred as potential influencers of autism. Knockout mouse models suggested the involvement of the CASP8, GABBR1, and PLEKHM1 genes in neurological processes. Our findings suggest 17 candidate therapeutic targets for ASD and provide novel drug targets for therapy development and critical drug repurposing opportunities., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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5. Spatial proximity and gene function: a new dimension in prokaryotic gene association network analysis with 3D-GeneNet.
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Gao Y, Ma B, Xu Q, Peng Y, Gong H, Guan A, Hua K, Langford PR, Jin H, and Luo R
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- Algorithms, Computational Biology methods, High-Throughput Nucleotide Sequencing methods, Escherichia coli K12 genetics, Escherichia coli K12 metabolism, Escherichia coli genetics, Escherichia coli metabolism, Gene Regulatory Networks, Software
- Abstract
Understanding the biological functions and processes of genes, particularly those not yet characterized, is crucial for advancing molecular biology and identifying therapeutic targets. The hypothesis guiding this study is that the 3D proximity of genes correlates with their functional interactions and relevance in prokaryotes. We introduced 3D-GeneNet, an innovative software tool that utilizes high-throughput sequencing data from chromosome conformation capture techniques and integrates topological metrics to construct gene association networks. Through a series of comparative analyses focused on spatial versus linear distances, we explored various dimensions such as topological structure, functional enrichment levels, distribution patterns of linear distances among gene pairs, and the area under the receiver operating characteristic curve by utilizing model organism Escherichia coli K-12. Furthermore, 3D-GeneNet was shown to maintain good accuracy compared to multiple algorithms (neighbourhood, co-occurrence, coexpression, and fusion) across multiple bacteria, including E. coli, Brucella abortus, and Vibrio cholerae. In addition, the accuracy of 3D-GeneNet's prediction of long-distance gene interactions was identified by bacterial two-hybrid assays on E. coli K-12 MG1655, where 3D-GeneNet not only increased the accuracy of linear genomic distance tripled but also achieved 60% accuracy by running alone. Finally, it can be concluded that the applicability of 3D-GeneNet will extend to various bacterial forms, including Gram-negative, Gram-positive, single-, and multi-chromosomal bacteria through Hi-C sequencing and analysis. Such findings highlight the broad applicability and significant promise of this method in the realm of gene association network. 3D-GeneNet is freely accessible at https://github.com/gaoyuanccc/3D-GeneNet., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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6. Development and validation of risk prediction model for recurrent cardiovascular events among Chinese: the Personalized CARdiovascular DIsease risk Assessment for Chinese model.
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Zhou Y, Lin CJ, Yu Q, Blais JE, Wan EYF, Lee M, Wong E, Siu DC, Wong V, Chan EWY, Lam TW, Chui W, Wong ICK, Luo R, and Chui CSL
- Abstract
Aims: Cardiovascular disease (CVD) is a leading cause of mortality, especially in developing countries. This study aimed to develop and validate a CVD risk prediction model, Personalized CARdiovascular DIsease risk Assessment for Chinese (P-CARDIAC), for recurrent cardiovascular events using machine learning technique., Methods and Results: Three cohorts of Chinese patients with established CVD were included if they had used any of the public healthcare services provided by the Hong Kong Hospital Authority (HA) since 2004 and categorized by their geographical locations. The 10-year CVD outcome was a composite of diagnostic or procedure codes with specific International Classification of Diseases, Ninth Revision, Clinical Modification. Multivariate imputation with chained equations and XGBoost were applied for the model development. The comparison with Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS-2°P) and Secondary Manifestations of ARTerial disease (SMART2) used the validation cohorts with 1000 bootstrap replicates. A total of 48 799, 119 672 and 140 533 patients were included in the derivation and validation cohorts, respectively. A list of 125 risk variables were used to make predictions on CVD risk, of which 8 classes of CVD-related drugs were considered interactive covariates. Model performance in the derivation cohort showed satisfying discrimination and calibration with a C statistic of 0.69. Internal validation showed good discrimination and calibration performance with C statistic over 0.6. The P-CARDIAC also showed better performance than TRS-2°P and SMART2., Conclusion: Compared with other risk scores, the P-CARDIAC enables to identify unique patterns of Chinese patients with established CVD. We anticipate that the P-CARDIAC can be applied in various settings to prevent recurrent CVD events, thus reducing the related healthcare burden., Competing Interests: Conflict of interest: E.Y.F.W. has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region and the Hong Kong Research Grants Council, outside the submitted work. E.W.Y.C. reports honorarium from Hospital Authority and grants from Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, outside the submitted work. I.C.K.W. reports research funding outside the submitted work from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council, the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, National Institute for Health Research in England, European Commission, and the National Health and Medical Research Council in Australia; has received speaker fees from Janssen and Medice in the previous 3 years; and is an independent non-executive director of Jacobson Medical in Hong Kong. C.S.L.C. has received grants from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, MSD, and Amgen and personal fees from PrimeVigilance, outside the submitted work. All other authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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- 2024
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7. Molecular phylogenetics of the Umbelopsis genus-identification of new species and evaluation of their oil application value.
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Hou D, Tang D, Wang Y, Zhu J, Luo R, Liu Z, Lu Y, Sun T, Ma Y, Zhang Y, and Yu H
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- Phylogeny, Eicosapentaenoic Acid, Fatty Acids, Unsaturated analysis, Docosahexaenoic Acids, Fish Oils chemistry, Biofuels
- Abstract
Aims: The aim of this study was to reconstruct the evolutionary framework of the genus Umbelopsis by using modern taxonomic strategies and evaluating the quality of oil and prospective uses of three distinct species., Methods and Results: Three species of Umbelopsis were identified based on morphological characteristics and phylogenetic evidence obtained from three genes (ITS, LSU, and ACT). A new species of Umbelopsis was described and illustrated, and subsequently named U. ophiocordycipiticola. The characteristics of U. ophiocordycipiticola exhibited sporangia with a diameter ranging from 8 to 17 µm. and sporangiospores that were oval to ellipsoidal in shape, irregularly angular, with dimensions of ∼1.9-2.9 × 1.7-3.0 µm. Gas chromatography and mass spectrometry (GC-MS) were used to examine the composition of fatty acids. Notably, U. ophiocordycipiticola showed a significantly higher oil content of 50.89% in dry cell weight (DCW) compared to U. vinacea and U. ramanniana. The mean proportion of polyunsaturated fatty acids (PUFAs) in U. ophiocordycipiticola was 32.38%, and the maximum levels of γ-linolenic acid (GLA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in U. ophiocordycipiticola were found to be 14.51, 0.24, 0.54, and 0.53%, respectively. The biodiesel quality from all three species complied with applicable standards set by the American Association for Testing and Materials (ASTM 6751) and the Brazilian National Petroleum Agency (ANP 255)., Conclusions: The establishment of a novel species, U. ophiocordycipiticola, was strongly supported by morphological and molecular evidence. Umbelopsis ophiocordycipiticola exhibited a high-value PUFA content. Additionally, three Umbelopsis species demonstrated good quality for biodiesel production., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)
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- 2024
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8. Bases-dependent Rapid Phylogenetic Clustering (Bd-RPC) enables precise and efficient phylogenetic estimation in viruses.
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Ma B, Gong H, Xu Q, Gao Y, Guan A, Wang H, Hua K, Luo R, and Jin H
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Understanding phylogenetic relationships among species is essential for many biological studies, which call for an accurate phylogenetic tree to understand major evolutionary transitions. The phylogenetic analyses present a major challenge in estimation accuracy and computational efficiency, especially recently facing a wave of severe emerging infectious disease outbreaks. Here, we introduced a novel, efficient framework called Bases-dependent Rapid Phylogenetic Clustering (Bd-RPC) for new sample placement for viruses. In this study, a brand-new recoding method called Frequency Vector Recoding was implemented to approximate the phylogenetic distance, and the Phylogenetic Simulated Annealing Search algorithm was developed to match the recoded distance matrix with the phylogenetic tree. Meanwhile, the indel (insertion/deletion) was heuristically introduced to foreign sequence recognition for the first time. Here, we compared the Bd-RPC with the recent placement software (PAGAN2, EPA-ng, TreeBeST) and evaluated it in Alphacoronavirus, Alphaherpesvirinae , and Betacoronavirus by using Split and Robinson-Foulds distances. The comparisons showed that Bd-RPC maintained the highest precision with great efficiency, demonstrating good performance in new sample placement on all three virus genera. Finally, a user-friendly website (http://www.bd-rpc.xyz) is available for users to classify new samples instantly and facilitate exploration of the phylogenetic research in viruses, and the Bd-RPC is available on GitHub (http://github.com/Bin-Ma/bd-rpc)., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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9. Improvements in Sperm Motility Following Low- or High-Intensity Dietary Interventions in Men With Obesity.
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Sharma A, Papanikolaou N, Abou Sherif S, Dimakopolou A, Thaventhiran T, Go C, Holtermann Entwistle O, Brown A, Luo R, Jha R, Prakash A, Khalifa D, Lewis H, Ramaraju S, Leeds AR, Chahal H, Purkayastha S, Henkel R, Minhas S, Frost G, Dhillo WS, and Jayasena CN
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- Male, Humans, Semen Analysis, Sperm Motility, Semen, Sperm Count, Spermatozoa, Obesity complications, Obesity surgery, Oligospermia, Infertility, Male etiology
- Abstract
Introduction: Obesity increases risks of male infertility, but bariatric surgery does not improve semen quality. Recent uncontrolled studies suggest that a low-energy diet (LED) improves semen quality. Further evaluation within a randomized, controlled setting is warranted., Methods: Men with obesity (18-60 years) with normal sperm concentration (normal count) (n = 24) or oligozoospermia (n = 43) were randomized 1:1 to either 800 kcal/day LED for 16 weeks or control, brief dietary intervention (BDI) with 16 weeks' observation. Semen parameters were compared at baseline and 16 weeks., Results: Mean age of men with normal count was 39.4 ± 6.4 in BDI and 40.2 ± 9.6 years in the LED group. Mean age of men with oligozoospermia was 39.5 ± 7.5 in BDI and 37.7 ± 6.6 years in the LED group. LED caused more weight loss than BDI in men with normal count (14.4 vs 6.3 kg; P < .001) and men with oligozoospermia (17.6 vs 1.8 kg; P < .001). Compared with baseline, in men with normal count total motility (TM) increased 48 ± 17% to 60 ± 10% (P < .05) after LED, and 52 ± 8% to 61 ± 6% (P < .0001) after BDI; progressive motility (PM) increased 41 ± 16% to 53 ± 10% (P < .05) after LED, and 45 ± 8% to 54 ± 65% (P < .001) after BDI. In men with oligozoospermia compared with baseline, TM increased 35% [26] to 52% [16] (P < .05) after LED, and 43% [28] to 50% [23] (P = .0587) after BDI; PM increased 29% [23] to 46% [18] (P < .05) after LED, and 33% [25] to 44% [25] (P < .05) after BDI. No differences in postintervention TM or PM were observed between LED and BDI groups in men with normal count or oligozoospermia., Conclusion: LED or BDI may be sufficient to improve sperm motility in men with obesity. The effects of paternal dietary intervention on fertility outcomes requires investigation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2024
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10. Viability of the rectus femoris muscle flap for groin wound coverage after ligation of proximal inflow.
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Julian O, Wilcox K, Sharma D, Lamb K, Luo R, Zheng H, Sooppan R, and Behnam A
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Lower extremity revascularization via groin incisions can be complicated by wound dehiscence associated with infection, seroma and femoral vessel exposure. This may require additional surgical debridement and coverage of vascular structures and grafts. The pedicled rectus femoris muscle flap (RFF) has both bulk and a large arc of rotation, making it useful for reconstruction. Its main pedicle is the descending branch of the lateral femoral circumflex artery (DLFCA), a branch of the profunda femoris artery. One could anticipate that ligation of more proximal vasculature could lead to ischemia of the RFF. We present two patients who each underwent vascular surgery involving the common femoral artery and subsequent reconstruction utilizing a pedicled RFF. Both patients then required additional vascular procedures involving the ligation of inflow vessels proximal to the DLFCA. The flaps remained viable, demonstrating the rich collateralization of blood supply that occurs in vascular disease patients., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)
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- 2024
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11. ClusterV-Web: a user-friendly tool for profiling HIV quasispecies and generating drug resistance reports from nanopore long-read data.
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Su J, Li S, Zheng Z, Lam TW, and Luo R
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Summary: Third-generation long-read sequencing is an increasingly utilized technique for profiling human immunodeficiency virus (HIV) quasispecies and detecting drug resistance mutations due to its ability to cover the entire viral genome in individual reads. Recently, the ClusterV tool has demonstrated accurate detection of HIV quasispecies from Nanopore long-read sequencing data. However, the need for scripting skills and a computational environment may act as a barrier for many potential users. To address this issue, we have introduced ClusterV-Web, a user-friendly web-based application that enables easy configuration and execution of ClusterV, both remotely and locally. Our tool provides interactive tables and data visualizations to aid in the interpretation of results. This development is expected to democratize access to long-read sequencing data analysis, enabling a wider range of researchers and clinicians to efficiently profile HIV quasispecies and detect drug resistance mutations., Availability and Implementation: ClusterV-Web is freely available and open source, with detailed documentation accessible at http://www.bio8.cs.hku.hk/ClusterVW/. The standalone Docker image and source code are also available at https://github.com/HKU-BAL/ClusterV-Web., Competing Interests: R.L. receives research funding from ONT. The other authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press.)
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- 2024
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12. StemDriver: a knowledgebase of gene functions for hematopoietic stem cell fate determination.
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Luo Y, Guo J, Wen J, Zhao W, Huang K, Liu Y, Wang G, Luo R, Niu T, Feng Y, Xu H, Kim P, and Zhou X
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- Animals, Humans, Mice, Gene Regulatory Networks, Reproducibility of Results, Knowledge Bases, Cell Lineage, Hematopoiesis genetics, Hematopoietic Stem Cells metabolism
- Abstract
StemDriver is a comprehensive knowledgebase dedicated to the functional annotation of genes participating in the determination of hematopoietic stem cell fate, available at http://biomedbdc.wchscu.cn/StemDriver/. By utilizing single-cell RNA sequencing data, StemDriver has successfully assembled a comprehensive lineage map of hematopoiesis, capturing the entire continuum from the initial formation of hematopoietic stem cells to the fully developed mature cells. Extensive exploration and characterization were conducted on gene expression features corresponding to each lineage commitment. At the current version, StemDriver integrates data from 42 studies, encompassing a diverse range of 14 tissue types spanning from the embryonic phase to adulthood. In order to ensure uniformity and reliability, all data undergo a standardized pipeline, which includes quality data pre-processing, cell type annotation, differential gene expression analysis, identification of gene categories correlated with differentiation, analysis of highly variable genes along pseudo-time, and exploration of gene expression regulatory networks. In total, StemDriver assessed the function of 23 839 genes for human samples and 29 533 genes for mouse samples. Simultaneously, StemDriver also provided users with reference datasets and models for cell annotation. We believe that StemDriver will offer valuable assistance to research focused on cellular development and hematopoiesis., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2024
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13. FusionNeoAntigen: a resource of fusion gene-specific neoantigens.
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Kumar H, Luo R, Wen J, Yang C, Zhou X, and Kim P
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- Humans, HLA Antigens, INDEL Mutation, Mutation, Antigens, Neoplasm genetics, Neoplasms genetics, Oncogene Proteins, Fusion genetics, Databases, Genetic
- Abstract
Among the diverse sources of neoantigens (i.e. single-nucleotide variants (SNVs), insertions or deletions (Indels) and fusion genes), fusion gene-derived neoantigens are generally more immunogenic, have multiple targets per mutation and are more widely distributed across various cancer types. Therefore, fusion gene-derived neoantigens are a potential source of highly immunogenic neoantigens and hold great promise for cancer immunotherapy. However, the lack of fusion protein sequence resources and knowledge prevents this application. We introduce 'FusionNeoAntigen', a dedicated resource for fusion-specific neoantigens, accessible at https://compbio.uth.edu/FusionNeoAntigen. In this resource, we provide fusion gene breakpoint crossing neoantigens focused on ∼43K fusion proteins of ∼16K in-frame fusion genes from FusionGDB2.0. FusionNeoAntigen provides fusion gene information, corresponding fusion protein sequences, fusion breakpoint peptide sequences, fusion gene-derived neoantigen prediction, virtual screening between fusion breakpoint peptides having potential fusion neoantigens and human leucocyte antigens (HLAs), fusion breakpoint RNA/protein sequences for developing vaccines, information on samples with fusion-specific neoantigen, potential CAR-T targetable cell-surface fusion proteins and literature curation. FusionNeoAntigen will help to develop fusion gene-based immunotherapies. We will report all potential fusion-specific neoantigens from all possible open reading frames of ∼120K human fusion genes in future versions., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2024
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14. Nonlinear function-on-scalar regression via functional universal approximation.
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Luo R and Qi X
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- Neural Networks, Computer, Nonlinear Dynamics
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We consider general nonlinear function-on-scalar (FOS) regression models, where the functional response depends on multiple scalar predictors in a general unknown nonlinear form. Existing methods either assume specific model forms (e.g., additive models) or directly estimate the nonlinear function in a space with dimension equal to the number of scalar predictors, which can only be applied to models with a few scalar predictors. To overcome these shortcomings, motivated by the classic universal approximation theorem used in neural networks, we develop a functional universal approximation theorem which can be used to approximate general nonlinear FOS maps and can be easily adopted into the framework of functional data analysis. With this theorem and utilizing smoothness regularity, we develop a novel method to fit the general nonlinear FOS regression model and make predictions. Our new method does not make any specific assumption on the model forms, and it avoids the direct estimation of nonlinear functions in a space with dimension equal to the number of scalar predictors. By estimating a sequence of bivariate functions, our method can be applied to models with a relatively large number of scalar predictors. The good performance of the proposed method is demonstrated by empirical studies on various simulated and real datasets., (© 2023 The International Biometric Society.)
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- 2023
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15. Long-Read Sequencing with Hierarchical Clustering for Antiretroviral Resistance Profiling of Mixed Human Immunodeficiency Virus Quasispecies.
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Ng TT, Su J, Lao HY, Lui WW, Chan CT, Leung AW, Jim SH, Lee LK, Shehzad S, Tam KK, Leung KS, Tang F, Yam WC, Luo R, and Siu GK
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- Humans, Quasispecies genetics, Anti-Retroviral Agents pharmacology, Anti-Retroviral Agents therapeutic use, Mutation, High-Throughput Nucleotide Sequencing methods, Cluster Analysis, HIV Infections drug therapy, HIV-1 genetics
- Abstract
Background: HIV infections often develop drug resistance mutations (DRMs), which can increase the risk of virological failure. However, it has been difficult to determine if minor mutations occur in the same genome or in different virions using Sanger sequencing and short-read sequencing methods. Oxford Nanopore Technologies (ONT) sequencing may improve antiretroviral resistance profiling by allowing for long-read clustering., Methods: A new ONT sequencing-based method for profiling DRMs in HIV quasispecies was developed and validated. The method used hierarchical clustering of long amplicons that cover regions associated with different types of antiretroviral drugs. A gradient series of an HIV plasmid and 2 plasma samples was prepared to validate the clustering performance. The ONT results were compared to those obtained with Sanger sequencing and Illumina sequencing in 77 HIV-positive plasma samples to evaluate the diagnostic performance., Results: In the validation study, the abundance of detected quasispecies was concordant with the predicted result with the R2 of > 0.99. During the diagnostic evaluation, 59/77 samples were successfully sequenced for DRMs. Among 18 failed samples, 17 were below the limit of detection of 303.9 copies/μL. Based on the receiver operating characteristic analysis, the ONT workflow achieved an F1 score of 0.96 with a cutoff of 0.4 variant allele frequency. Four cases were found to have quasispecies with DRMs, in which 2 harbored quasispecies with more than one class of DRMs. Treatment modifications were recommended for these cases., Conclusions: Long-read sequencing coupled with hierarchical clustering could differentiate the quasispecies resistance profiles in HIV-infected samples, providing a clearer picture for medical care., (© American Association for Clinical Chemistry 2023.)
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- 2023
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16. Development and Validation of a Deep Learning-Based Histologic Diagnosis System for Diagnosing Colorectal Sessile Serrated Lesions.
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Wu Z, Yao L, Liu W, Zhang S, Zhang L, Lu Z, Wang J, Chen B, Luo R, Li X, Gong R, Luo C, Xu Y, Zeng Z, and Yu H
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- Humans, Artificial Intelligence, Neural Networks, Computer, Colonic Polyps diagnosis, Colonic Polyps pathology, Deep Learning, Colorectal Neoplasms diagnosis, Colorectal Neoplasms pathology
- Abstract
Objectives: The histopathologic diagnosis of colorectal sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) is of low consistency among pathologists. This study aimed to develop and validate a deep learning (DL)-based logical anthropomorphic pathology diagnostic system (LA-SSLD) for the differential diagnosis of colorectal SSL and HP., Methods: The diagnosis framework of the LA-SSLD system was constructed according to the current guidelines and consisted of 4 DL models. Deep convolutional neural network (DCNN) 1 was the mucosal layer segmentation model, DCNN 2 was the muscularis mucosa segmentation model, DCNN 3 was the glandular lumen segmentation model, and DCNN 4 was the glandular lumen classification (aberrant or regular) model. A total of 175 HP and 127 SSL sections were collected from Renmin Hospital of Wuhan University during November 2016 to November 2022. The performance of the LA-SSLD system was compared to 11 pathologists with different qualifications through the human-machine contest., Results: The Dice scores of DCNNs 1, 2, and 3 were 93.66%, 58.38%, and 74.04%, respectively. The accuracy of DCNN 4 was 92.72%. In the human-machine contest, the accuracy, sensitivity, and specificity of the LA-SSLD system were 85.71%, 86.36%, and 85.00%, respectively. In comparison with experts (pathologist D: accuracy 83.33%, sensitivity 90.91%, specificity 75.00%; pathologist E: accuracy 85.71%, sensitivity 90.91%, specificity 80.00%), LA-SSLD achieved expert-level accuracy and outperformed all the senior and junior pathologists., Conclusions: This study proposed a logical anthropomorphic diagnostic system for the differential diagnosis of colorectal SSL and HP. The diagnostic performance of the system is comparable to that of experts and has the potential to become a powerful diagnostic tool for SSL in the future. It is worth mentioning that a logical anthropomorphic system can achieve expert-level accuracy with fewer samples, providing potential ideas for the development of other artificial intelligence models., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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17. Systematic investigation of the homology sequences around the human fusion gene breakpoints in pan-cancer - bioinformatics study for a potential link to MMEJ.
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Kim P, Kumar H, Yang C, Luo R, Liu J, and Zhou X
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- Humans, Genomics, Exons, Genomic Instability, Computational Biology, Neoplasms genetics
- Abstract
Microhomology-mediated end joining (MMEJ), an error-prone DNA damage repair mechanism, frequently leads to chromosomal rearrangements due to its ability to engage in promiscuous end joining of genomic instability and also leads to increasing mutational load at the sequences flanking the breakpoints (BPs). In this study, we systematically investigated the homology sequences around the genomic breakpoint area of human fusion genes, which were formed by the chromosomal rearrangements initiated by DNA double-strand breakage. Since the RNA-seq data is the typical data set to check the fusion genes, for the known exon junction fusion breakpoints identified from RNA-seq data, we have to infer the high chance of genomic breakpoint regions. For this, we utilized the high feature importance score area calculated from our recently developed fusion BP prediction model, FusionAI and identified 151 K microhomologies among ~24 K fusion BPs in 20 K fusion genes. From our multiple bioinformatics studies, we found a relationship between sequence homologies and the immune system. This in-silico study will provide novel knowledge on the sequence homologies around the coded structural variants., (© The Author(s) 2023. Published by Oxford University Press.)
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- 2023
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18. Abrocitinib as a novel treatment for lichen sclerosus.
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Bao C, Xu Q, Xiao Z, Wang H, Luo R, Cheng B, Ji C, and Gong T
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- Humans, Female, Pyrimidines, Sulfonamides, Lichen Sclerosus et Atrophicus drug therapy, Vulvar Lichen Sclerosus drug therapy
- Abstract
Competing Interests: Conflicts of interest The authors declare they have no conflicts of interest.
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- 2023
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19. SMDB: a Spatial Multimodal Data Browser.
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Cao R, Ling Y, Meng J, Jiang A, Luo R, He Q, Li A, Chen Y, Zhang Z, Liu F, Li Y, and Zhang G
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- Animals, Mice, Brain anatomy & histology, Transcriptome, Gene Expression Profiling, Software
- Abstract
Understanding the relationship between fine-scale spatial organization and biological function necessitates a tool that effectively combines spatial positions, morphological information, and spatial transcriptomics (ST) data. We introduce the Spatial Multimodal Data Browser (SMDB, https://www.biosino.org/smdb), a robust visualization web service for interactively exploring ST data. By integrating multimodal data, such as hematoxylin and eosin (H&E) images, gene expression-based molecular clusters, and more, SMDB facilitates the analysis of tissue composition through the dissociation of two-dimensional (2D) sections and the identification of gene expression-profiled boundaries. In a digital three-dimensional (3D) space, SMDB allows researchers to reconstruct morphology visualizations based on manually filtered spots or expand anatomical structures using high-resolution molecular subtypes. To enhance user experience, it offers customizable workspaces for interactive exploration of ST spots in tissues, providing features like smooth zooming, panning, 360-degree rotation in 3D and adjustable spot scaling. SMDB is particularly valuable in neuroscience and spatial histology studies, as it incorporates Allen's mouse brain anatomy atlas for reference in morphological research. This powerful tool provides a comprehensive and efficient solution for examining the intricate relationships between spatial morphology, and biological function in various tissues., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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- 2023
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20. Identification of candidate genes that regulate the trade-off between seedling cold tolerance and fruit quality in melon ( Cucumis melo L.).
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Li L, Li Q, Chen B, Wang J, Ding F, Wang P, Zhang X, Hou J, Luo R, Li X, Zheng J, Yang S, Yang L, Zhu L, Sun S, Ma C, Li Q, Li Y, and Hu J
- Abstract
Trade-offs between survival and growth are widely observed in plants. Melon is an annual, trailing herb that produces economically valuable fruits that are traditionally cultivated in early spring in China. Melon seedlings are sensitive to low temperatures, and thus usually suffer from cold stress during the early growth period. However, little is known about the mechanism behind the trade-offs between seedling cold tolerance and fruit quality in melon. In this study, a total of 31 primary metabolites were detected from the mature fruits of eight melon lines that differ with respect to seedling cold tolerance; these included 12 amino acids, 10 organic acids, and 9 soluble sugars. Our results showed that concentrations of most of the primary metabolites in the cold-resistant melons were generally lower than in the cold-sensitive melons; the greatest difference in metabolite levels was observed between the cold-resistant line H581 and the moderately cold-resistant line HH09. The metabolite and transcriptome data for these two lines were then subjected to weighted correlation network analysis, resulting in the identification of five key candidate genes underlying the balancing between seedling cold tolerance and fruit quality. Among these genes, CmEAF7 might play multiple roles in regulating chloroplast development, photosynthesis, and the ABA pathway. Furthermore, multi-method functional analysis showed that CmEAF7 can certainly improve both seedling cold tolerance and fruit quality in melon. Our study identified an agriculturally important gene, CmEAF7 , and provides a new insight into breeding methods to develop melon cultivars with seedling cold tolerance and high fruit quality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the outcome of the research reported in this paper., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.)
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- 2023
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21. ACROBAT Edge: Safety and Efficacy of Switching Injected SRLs to Oral Paltusotine in Patients With Acromegaly.
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Gadelha MR, Gordon MB, Doknic M, Mezősi E, Tóth M, Randeva H, Marmon T, Jochelson T, Luo R, Monahan M, Madan A, Ferrara-Cook C, Struthers RS, and Krasner A
- Subjects
- Humans, Octreotide therapeutic use, Insulin-Like Growth Factor I metabolism, Prospective Studies, Peptides, Cyclic adverse effects, Treatment Outcome, Acromegaly drug therapy, Acromegaly metabolism, Human Growth Hormone
- Abstract
Context: Paltusotine is a once-daily, oral, nonpeptide small-molecule somatostatin receptor type 2 (SST2) agonist in clinical development for treatment of acromegaly., Objective: This work aimed to evaluate change in insulin-like growth factor I (IGF-I) levels in patients switched from octreotide long-acting release or lanreotide depot monotherapy to paltusotine., Methods: A phase 2, open-label, prospective, multicenter, multinational, nonrandomized, single-arm exploratory study was conducted in which dosage uptitrations were performed in a double-blinded manner. At 26 global sites, patients with acromegaly switched to paltusotine from injected somatostatin receptor ligand (SRL)-based therapy. Patients received 13-week treatment with once-daily oral paltusotine (10-40 mg/d). The primary end point was change from baseline to week 13 in IGF-I for patients who switched from long-acting octreotide or lanreotide depot monotherapy to paltusotine (group 1). All patients underwent a 4-week paltusotine washout at end of treatment period (wk 13-17). IGF-I, growth hormone (GH), patient-reported outcome, and safety data were collected., Results: Forty-seven patients enrolled. In group 1 (n = 25), IGF-I and GH showed no significant change between SRL baseline and end of paltusotine treatment at week 13 (median change in IGF-I = -0.03×upper limit of normal [ULN]; P = .6285; GH = -0.05 ng/mL; P = .6285). IGF-I and GH rose significantly in the 4 weeks after withdrawing paltusotine (median change in IGF-I = 0.55×ULN; P < .0001 [median increase 39%]; GH = 0.72 ng/mL; P < .0001 [109.1% increase]). No patients discontinued because of adverse events (AE); no treatment-related serious AEs were reported., Conclusion: These results suggest once-daily oral paltusotine was effective in maintaining IGF-I values in patients with acromegaly who switched from injected SRLs. Paltusotine was well tolerated with a safety profile consistent with other SRLs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2023
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22. Integrated mRNA sequence optimization using deep learning.
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Gong H, Wen J, Luo R, Feng Y, Guo J, Fu H, and Zhou X
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- Humans, RNA, Messenger genetics, RNA, Messenger metabolism, Base Sequence, Amino Acid Sequence, Deep Learning, COVID-19 genetics
- Abstract
The coronavirus disease of 2019 pandemic has catalyzed the rapid development of mRNA vaccines, whereas, how to optimize the mRNA sequence of exogenous gene such as severe acute respiratory syndrome coronavirus 2 spike to fit human cells remains a critical challenge. A new algorithm, iDRO (integrated deep-learning-based mRNA optimization), is developed to optimize multiple components of mRNA sequences based on given amino acid sequences of target protein. Considering the biological constraints, we divided iDRO into two steps: open reading frame (ORF) optimization and 5' untranslated region (UTR) and 3'UTR generation. In ORF optimization, BiLSTM-CRF (bidirectional long-short-term memory with conditional random field) is employed to determine the codon for each amino acid. In UTR generation, RNA-Bart (bidirectional auto-regressive transformer) is proposed to output the corresponding UTR. The results show that the optimized sequences of exogenous genes acquired the pattern of human endogenous gene sequence. In experimental validation, the mRNA sequence optimized by our method, compared with conventional method, shows higher protein expression. To the best of our knowledge, this is the first study by introducing deep-learning methods to integrated mRNA sequence optimization, and these results may contribute to the development of mRNA therapeutics., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
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- 2023
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23. Assembly-free discovery of human novel sequences using long reads.
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Li Q, Yan B, Lam TW, and Luo R
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- Humans, Sequence Analysis, DNA methods, Base Sequence, Genomics, High-Throughput Nucleotide Sequencing methods, Nanopores
- Abstract
DNA sequences that are absent in the human reference genome are classified as novel sequences. The discovery of these missed sequences is crucial for exploring the genomic diversity of populations and understanding the genetic basis of human diseases. However, various DNA lengths of reads generated from different sequencing technologies can significantly affect the results of novel sequences. In this work, we designed an assembly-free novel sequence (AF-NS) approach to identify novel sequences from Oxford Nanopore Technology long reads. Among the newly detected sequences using AF-NS, more than 95% were omitted from those using long-read assemblers and 85% were not present in short reads of Illumina. We identified the common novel sequences among all the samples and revealed their association with the binding motifs of transcription factors. Regarding the placements of the novel sequences, we found about 70% enriched in repeat regions and generated 430 for one specific subpopulation that might be related to their evolution. Our study demonstrates the advance of the assembly-free approach to capture more novel sequences over other assembler based methods. Combining the long-read data with powerful analytical methods can be a robust way to improve the completeness of novel sequences., (© The Author(s) 2022. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)
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- 2022
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24. BioGPT: generative pre-trained transformer for biomedical text generation and mining.
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Luo R, Sun L, Xia Y, Qin T, Zhang S, Poon H, and Liu TY
- Subjects
- Data Mining, Natural Language Processing
- Abstract
Pre-trained language models have attracted increasing attention in the biomedical domain, inspired by their great success in the general natural language domain. Among the two main branches of pre-trained language models in the general language domain, i.e. BERT (and its variants) and GPT (and its variants), the first one has been extensively studied in the biomedical domain, such as BioBERT and PubMedBERT. While they have achieved great success on a variety of discriminative downstream biomedical tasks, the lack of generation ability constrains their application scope. In this paper, we propose BioGPT, a domain-specific generative Transformer language model pre-trained on large-scale biomedical literature. We evaluate BioGPT on six biomedical natural language processing tasks and demonstrate that our model outperforms previous models on most tasks. Especially, we get 44.98%, 38.42% and 40.76% F1 score on BC5CDR, KD-DTI and DDI end-to-end relation extraction tasks, respectively, and 78.2% accuracy on PubMedQA, creating a new record. Our case study on text generation further demonstrates the advantage of BioGPT on biomedical literature to generate fluent descriptions for biomedical terms., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
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- 2022
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25. Clair3-trio: high-performance Nanopore long-read variant calling in family trios with trio-to-trio deep neural networks.
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Su J, Zheng Z, Ahmed SS, Lam TW, and Luo R
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- Genomics methods, High-Throughput Nucleotide Sequencing methods, Humans, Neural Networks, Computer, Sequence Analysis, DNA, Software, Nanopores
- Abstract
Accurate identification of genetic variants from family child-mother-father trio sequencing data is important in genomics. However, state-of-the-art approaches treat variant calling from trios as three independent tasks, which limits their calling accuracy for Nanopore long-read sequencing data. For better trio variant calling, we introduce Clair3-Trio, the first variant caller tailored for family trio data from Nanopore long-reads. Clair3-Trio employs a Trio-to-Trio deep neural network model, which allows it to input the trio sequencing information and output all of the trio's predicted variants within a single model to improve variant calling. We also present MCVLoss, a novel loss function tailor-made for variant calling in trios, leveraging the explicit encoding of the Mendelian inheritance. Clair3-Trio showed comprehensive improvement in experiments. It predicted far fewer Mendelian inheritance violation variations than current state-of-the-art methods. We also demonstrated that our Trio-to-Trio model is more accurate than competing architectures. Clair3-Trio is accessible as a free, open-source project at https://github.com/HKU-BAL/Clair3-Trio., (© The Author(s) 2022. Published by Oxford University Press.)
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- 2022
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26. Restricted function-on-function linear regression model.
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Luo R and Qi X
- Subjects
- Linear Models, Algorithms
- Abstract
The usual function-on-function linear regression model depicts the association between functional variables in the whole rectangular region and the value of response curve at any point is influenced by the entire trajectory of the predictor curve. But in addition to this, there are cases where the value of the response curve at a point is only influenced by the value of the predictor curve in a subregion, such as the historical relationship and the short-term association. We will consider the restricted function-on-function regression model, where the value of response curve at any point is influenced by a subtrajectory of the predictor. We have two major purposes. First, we propose a novel estimation procedure that is more accurate and computational efficient for the restricted function-on-function model with a given subregion. Second, as the subregion is seldom specified in practice, we propose a subregion selection procedure that can lead to models with better interpretation and predictive performance. Algorithms are developed for both model estimation and subregion selection., (© 2021 The International Biometric Society.)
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- 2022
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27. Molecular basis and homeostatic regulation of Zinc taste.
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Luo R, Zhang Y, Jia Y, Zhang Y, Li Z, Zhao J, Liu T, and Zhang W
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- Homeostasis, Taste physiology, Zinc
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- 2022
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28. De Novo Assembly of 20 Chicken Genomes Reveals the Undetectable Phenomenon for Thousands of Core Genes on Microchromosomes and Subtelomeric Regions.
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Li M, Sun C, Xu N, Bian P, Tian X, Wang X, Wang Y, Jia X, Heller R, Wang M, Wang F, Dai X, Luo R, Guo Y, Wang X, Yang P, Hu D, Liu Z, Fu W, Zhang S, Li X, Wen C, Lan F, Siddiki AZ, Suwannapoom C, Zhao X, Nie Q, Hu X, Jiang Y, and Yang N
- Subjects
- Animals, Genomics, Mammals genetics, Sequence Analysis, DNA, Chickens genetics, Genome
- Abstract
The gene numbers and evolutionary rates of birds were assumed to be much lower than those of mammals, which is in sharp contrast to the huge species number and morphological diversity of birds. It is, therefore, necessary to construct a complete avian genome and analyze its evolution. We constructed a chicken pan-genome from 20 de novo assembled genomes with high sequencing depth, and identified 1,335 protein-coding genes and 3,011 long noncoding RNAs not found in GRCg6a. The majority of these novel genes were detected across most individuals of the examined transcriptomes but were seldomly measured in each of the DNA sequencing data regardless of Illumina or PacBio technology. Furthermore, different from previous pan-genome models, most of these novel genes were overrepresented on chromosomal subtelomeric regions and microchromosomes, surrounded by extremely high proportions of tandem repeats, which strongly blocks DNA sequencing. These hidden genes were proved to be shared by all chicken genomes, included many housekeeping genes, and enriched in immune pathways. Comparative genomics revealed the novel genes had 3-fold elevated substitution rates than known ones, updating the knowledge about evolutionary rates in birds. Our study provides a framework for constructing a better chicken genome, which will contribute toward the understanding of avian evolution and the improvement of poultry breeding., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)
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- 2022
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29. HKG: an open genetic variant database of 205 Hong Kong cantonese exomes.
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Ou M, Leung HC, Leung AW, Luk HM, Yan B, Liu CM, Tong TM, Mok MT, Ko WM, Law WC, Lam TW, Lo IF, and Luo R
- Abstract
HKG is the first fully accessible variant database for Hong Kong Cantonese, constructed from 205 novel whole-exome sequencing data. There has long been a research gap in the understanding of the genetic architecture of southern Chinese subgroups, including Hong Kong Cantonese. HKG detected 196 325 high-quality variants with 5.93% being novel, and 25 472 variants were found to be unique in HKG compared to three Chinese populations sampled from 1000 Genomes (CHN). PCA illustrates the uniqueness of HKG in CHN, and the admixture study estimated the ancestral composition of HKG and CHN, with a gradient change from north to south, consistent with their geological distribution. ClinVar, CIViC and PharmGKB annotated 599 clinically significant variants and 360 putative loss-of-function variants, substantiating our understanding of population characteristics for future medical development. Among the novel variants, 96.57% were singleton and 6.85% were of high impact. With a good representation of Hong Kong Cantonese, we demonstrated better variant imputation using reference with the addition of HKG data, thus successfully filling the data gap in southern Chinese to facilitate the regional and global development of population genetics., (© The Author(s) 2022. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)
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- 2022
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30. Association of prenatal acetaminophen use and acetaminophen metabolites with DNA methylation of newborns: analysis of two consecutive generations of the Isle of Wight birth cohort.
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Eslamimehr S, Jones AD, Anthony TM, Arshad SH, Holloway JW, Ewart S, Luo R, Mukherjee N, Kheirkhah Rahimabad P, Chen S, and Karmaus W
- Abstract
Acetaminophen is used by nearly two-thirds of pregnant women. Although considered safe, studies have demonstrated associations between prenatal acetaminophen use and adverse health outcomes in offspring. Since DNA methylation (DNAm) at birth may act as an early indicator of later health, assessments on whether DNAm of newborns is associated with gestational acetaminophen use or its metabolites are needed. Using data from three consecutive generations of the Isle of Wight cohort (F0-grandmothers, F1-mothers, and F2-offspring) we investigated associations between acetaminophen metabolites in F0 serum at delivery with epigenome-wide DNAm in F1 (Guthrie cards) and between acetaminophen use of F1 and F2-cord-serum levels with F2 cord blood DNAm. In epigenome-wide screening, we eliminated non-informative DNAm sites followed by linear regression of informative sites. Based on repeated pregnancies, indication bias analyses tested whether acetaminophen indicated maternal diseases or has a risk in its own right. Considering that individuals with similar intake process acetaminophen differently, metabolites were clustered to distinguish metabolic exposures. Finally, metabolite clusters from F1-maternal and F2-cord sera were tested for their associations with newborn DNAm (F1 and F2). Twenty-one differential DNAm sites in cord blood were associated with reported maternal acetaminophen intake in the F2 generation. For 11 of these cytosine-phosphate-guanine (CpG) sites, an indication bias was excluded and five were replicated in F2 with metabolite clusters. In addition, metabolite clusters showed associations with 25 CpGs in the F0-F1 discovery analysis, of which five CpGs were replicated in the F2-generation. Our results suggest that prenatal acetaminophen use, measured as metabolites, may influence DNAm in newborns., (Published by Oxford University Press 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)
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- 2022
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31. Distinct Disease Severity Between Children and Older Adults With Coronavirus Disease 2019 (COVID-19): Impacts of ACE2 Expression, Distribution, and Lung Progenitor Cells.
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Zhang Z, Guo L, Huang L, Zhang C, Luo R, Zeng L, Liang H, Li Q, Lu X, Wang X, Ma CY, Shao J, Luo W, Li L, Liu L, Li Z, Zhou X, Zhang X, Liu J, Yang J, Kwan KY, Liu W, Xu Y, Jiang H, Liu H, Du H, Wu Y, Yu G, Chen J, Wu J, Zhang J, Liao C, Chen HJ, Chen Z, Tse HF, Xia H, and Lian Q
- Subjects
- Aged, Child, Humans, Lung cytology, Middle Aged, RNA-Seq, Retrospective Studies, Severity of Illness Index, Angiotensin-Converting Enzyme 2 genetics, COVID-19, Stem Cells
- Abstract
Background: Children and older adults with coronavirus disease 2019 (COVID-19) display a distinct spectrum of disease severity yet the risk factors aren't well understood. We sought to examine the expression pattern of angiotensin-converting enzyme 2 (ACE2), the cell-entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the role of lung progenitor cells in children and older patients., Methods: We retrospectively analyzed clinical features in a cohort of 299 patients with COVID-19. The expression and distribution of ACE2 and lung progenitor cells were systematically examined using a combination of public single-cell RNA-seq data sets, lung biopsies, and ex vivo infection of lung tissues with SARS-CoV-2 pseudovirus in children and older adults. We also followed up patients who had recovered from COVID-19., Results: Compared with children, older patients (>50 years.) were more likely to develop into serious pneumonia with reduced lymphocytes and aberrant inflammatory response (P = .001). The expression level of ACE2 and lung progenitor cell markers were generally decreased in older patients. Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (P < .01). The follow-up of discharged patients revealed a prolonged recovery from pneumonia in the older (P < .025)., Conclusions: Compared to children, ACE2 positive cells are generally decreased in older adults and mainly presented in the lower pulmonary tract. The lung progenitor cells are also decreased. These risk factors may impact disease severity and recovery from pneumonia caused by SARS-Cov-2 infection in older patients., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2021
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32. Identification of genetic variations associated with drug resistance in non-small cell lung cancer patients undergoing systemic treatment.
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Luo R, Ge C, Xiao X, Song J, Miao S, Tang Y, Lai J, Nian W, Song F, and Ran L
- Subjects
- Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung mortality, Computational Biology methods, DNA Copy Number Variations, DNA Methylation, Databases, Genetic, Epigenesis, Genetic, Female, Genomics methods, Humans, Lung Neoplasms diagnosis, Lung Neoplasms drug therapy, Lung Neoplasms mortality, Male, Middle Aged, Molecular Sequence Annotation, Mutation, Prognosis, Transcriptome, Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung genetics, Drug Resistance, Neoplasm genetics, Genetic Variation, Lung Neoplasms genetics
- Abstract
Non-small cell lung cancer (NSCLC) is characterized by relatively rapid response to systemic treatments yet inevitable resistance and predisposed to distant metastasis. We thus aimed at performing sequencing analysis to determine genomic events and underlying mechanisms concerning drug resistance in NSCLC. We performed targeted sequencing of 40 medication-relevant genes on plasma samples from 98 NSCLC patients and analyzed impact of genetic alterations on clinical presentation as well as response to systemic treatments. Profiling of multi-omics data from 1024 NSCLC tissues in public datasets was carried out for comparison and validation of identified molecular events implicated in resistance. A genetic association of CYP2D6 deletion with drug resistance was identified through circulating tumor DNA (ctDNA) profiling and response assessment. FCGR3A amplification was potentially involved in resistance to EGFR inhibitors. We further verified our findings in tissue samples and focused on potential resistance mechanisms, which uncovered that depleted CYP2D6 affected a set of genes involved in EMT, oncogenic signaling as well as inflammatory pathways. Tumor microenvironment analysis revealed that NSCLC with CYP2D6 loss manifested increased levels of immunomodulatory gene expressions, PD-L1 expression, relatively high mutational burden and lymphocyte infiltration. DNA methylation alterations were also found to be correlated with mRNA expressions and copy numbers of CYP2D6. Finally, MEK inhibitors were identified by CMap as the prospective therapeutic drugs for CYP2D6 deletion. These analyses identified novel resistance mechanisms to systemic NSCLC treatments and had significant implications for the development of new treatment strategies., (© The Author(s) 2021. Published by Oxford University Press.)
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- 2021
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33. RENET2: high-performance full-text gene-disease relation extraction with iterative training data expansion.
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Su J, Wu Y, Ting HF, Lam TW, and Luo R
- Abstract
Relation extraction (RE) is a fundamental task for extracting gene-disease associations from biomedical text. Many state-of-the-art tools have limited capacity, as they can extract gene-disease associations only from single sentences or abstract texts. A few studies have explored extracting gene-disease associations from full-text articles, but there exists a large room for improvements. In this work, we propose RENET2, a deep learning-based RE method, which implements Section Filtering and ambiguous relations modeling to extract gene-disease associations from full-text articles. We designed a novel iterative training data expansion strategy to build an annotated full-text dataset to resolve the scarcity of labels on full-text articles. In our experiments, RENET2 achieved an F1-score of 72.13% for extracting gene-disease associations from an annotated full-text dataset, which was 27.22, 30.30, 29.24 and 23.87% higher than BeFree, DTMiner, BioBERT and RENET, respectively. We applied RENET2 to (i) ∼1.89M full-text articles from PubMed Central and found ∼3.72M gene-disease associations; and (ii) the LitCovid articles and ranked the top 15 proteins associated with COVID-19, supported by recent articles. RENET2 is an efficient and accurate method for full-text gene-disease association extraction. The source-code, manually curated abstract/full-text training data, and results of RENET2 are available at GitHub., (© The Author(s) 2021. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)
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- 2021
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34. Diagnostic efficacy of joint ultrasonography, dual-energy computed tomography and minimally invasive arthroscopy on knee gouty arthritis, a comparative study.
- Author
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Xie Y, Li L, Luo R, Xu T, Yang L, Xu F, Lin H, Zhang G, and Zhang X
- Subjects
- Female, Humans, Male, Middle Aged, Odds Ratio, Prospective Studies, Sensitivity and Specificity, Synovial Fluid chemistry, Arthritis, Gouty diagnostic imaging, Arthroscopy methods, Knee Joint diagnostic imaging, Tomography, X-Ray Computed methods, Ultrasonography methods, Uric Acid analysis
- Abstract
Objective: This study aimed to investigate the diagnostic performance of minimally invasive arthroscopy for knee gout when comparing with joint ultrasonography and dual-energy computed tomography (DECT)., Methods: From January 2016 to December 2018, 121 inpatients with knee joint swelling and pain were prospectively enrolled, including 63 gout patients and 58 non-gout patients. All patients underwent pre-operative ultrasonography and DECT to evaluate knee joint monosodium urate (MSU) deposits, followed by minimally invasive arthroscopy. The gold-standard for gout diagnosis was defined as the detection of MSU crystals in the synovial fluid under polarizing microscopic or pathological analysis., Results: The diagnostic results of ultrasonic double contour sign, hyperechogenic foci, MSU deposition (detected by DECT), MSU deposition (detected by arthroscopy) and MSU deposition in cartilage (detected by arthroscopy) were significantly associated with that of the gold-standard. Except for hyperechogenic foci, the other four indexes had high sensitivity and specificity (approximately or over 80%) and a large odds ratio (OR) (14.73 to 36.56), indicating good diagnostic performance. Detection of MSU deposition in cartilage by arthroscopy had a good diagnostic agreement with the ultrasonic double contour sign (κ = 0.711, p < 0.001)., Conclusion: Joint ultrasonography, DECT, and minimally invasive arthroscopy had high sensitivity and specificity for the diagnosis of knee gouty arthritis. Minimally invasive arthroscopy was superior to joint ultrasonography and DECT, which can be a useful supplement for the diagnosis of gout., Advances in Knowledge: This is the first study comparing the diagnostic performance for knee gout among the joint ultrasonography, DECT, and minimally invasive arthroscopy.
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- 2021
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35. The effects of oral treatment for systemic sclerosis related pulmonary arterial hypertension: A systematic review and meta-analysis.
- Author
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Lei Y, Zhang X, Lin H, Feng Y, Wang J, and Luo R
- Subjects
- Administration, Oral, Drug Therapy, Combination, Humans, Endothelin Receptor Antagonists pharmacology, Phosphodiesterase 5 Inhibitors pharmacology, Prostaglandins, Synthetic pharmacology, Pulmonary Arterial Hypertension drug therapy, Pulmonary Arterial Hypertension etiology, Pulmonary Arterial Hypertension physiopathology, Scleroderma, Systemic complications
- Abstract
Objectives: The usage of oral therapies, endothelin receptor antagonists (ERAs), phosphodiesterase type-5 (PDE-5) inhibitors and prostaglandin analogs has resulted in improved outcomes in patients with pulmonary arterial hypertension related to systemic sclerosis (SSc-PAH). However, the optimal therapeutics have not been determined., Methods: A systematic searching in the databases of Medline (PubMed), Embase, the Cochrane Library (Central) and unpublished clinical trials ( clinicaltrials.gov ) was conducted to identify the clinical studies with oral treatment for SSc-PAH patients published before 1 June 2019. The data were extracted and the quality was assessed. The main outcomes are exercise capacity and hemodynamic parameters, which were synthesized and analyzed., Results: In total, 27 clinical trials were enrolled for further analysis. It was demonstrated that bosentan treatment, the widely used drug for PAH, might improve the exercise capacity and pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in this clinical setting, although without significant difference. Meanwhile, the usage of prostaglandin analogs could improve the parameters mentioned above. Furthermore, combined therapy with ambrisentan and tadalafil significantly increased the treatment efficacy of key parameters in SSc-PAH patients compared with basic treatment., Conclusion: This meta-analysis reveals that combination therapy might provide more benefits to exercise capacity and hemodynamic parameters in SSc-PAH patients. Still more RCTs are needed to provide more solid evidence.
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- 2021
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36. Alterations of the Gut Microbiota in Patients With Coronavirus Disease 2019 or H1N1 Influenza.
- Author
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Gu S, Chen Y, Wu Z, Chen Y, Gao H, Lv L, Guo F, Zhang X, Luo R, Huang C, Lu H, Zheng B, Zhang J, Yan R, Zhang H, Jiang H, Xu Q, Guo J, Gong Y, Tang L, and Li L
- Subjects
- Cross-Sectional Studies, Dysbiosis, Feces, Humans, RNA, Ribosomal, 16S genetics, SARS-CoV-2, COVID-19, Gastrointestinal Microbiome, Influenza A Virus, H1N1 Subtype genetics, Influenza, Human
- Abstract
Background: Coronavirus disease 2019 (COVID-19) is an emerging serious global health problem. Gastrointestinal symptoms are common in COVID-19 patients, and severe acute respiratory syndrome coronavirus 2 RNA has been detected in stool specimens. However, the relationship between the gut microbiome and disease remains to be established., Methods: We conducted a cross-sectional study of 30 patients with COVID-19, 24 patients with influenza A(H1N1), and 30 matched healthy controls (HCs) to identify differences in the gut microbiota by 16S ribosomal RNA gene V3-V4 region sequencing., Results: Compared with HCs, COVID-19 patients had significantly reduced bacterial diversity; a significantly higher relative abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella, and Actinomyces; and a lower relative abundance of beneficial symbionts. Five biomarkers showed high accuracy for distinguishing COVID-19 patients from HCs with an area under the curve (AUC) up to 0.89. Patients with H1N1 displayed lower diversity and different overall microbial composition compared with COVID-19 patients. Seven biomarkers were selected to distinguish the 2 cohorts (AUC = 0.94)., Conclusions: The gut microbial signature of patients with COVID-19 was different from that of H1N1 patients and HCs. Our study suggests the potential value of the gut microbiota as a diagnostic biomarker and therapeutic target for COVID-19, but further validation is needed., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Published
- 2020
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37. Impact of Lymphovascular Invasion on Survival Outcome in Patients With Gastric Cancer.
- Author
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Mei D, Zhao B, Zhang J, Luo R, Lu H, Xu H, and Huang B
- Subjects
- Adenocarcinoma mortality, Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell mortality, Female, Humans, Male, Middle Aged, Neoplasm Staging, Prognosis, Retrospective Studies, Stomach Neoplasms mortality, Survival Rate, Young Adult, Adenocarcinoma pathology, Carcinoma, Squamous Cell pathology, Lymphatic Metastasis pathology, Neoplasm Invasiveness pathology, Stomach Neoplasms pathology
- Abstract
Objectives: To evaluate the prognostic significance of lymphovascular invasion (LVI) for patients with gastric cancer (GC)., Methods: A total of 1,720 consecutive patients who underwent curative gastrectomy were retrospectively identified. The association between LVI and clinicopathologic characteristics was determined and its impact on survival outcome was evaluated., Results: LVI was detected in 21.3% of GC patients, 5.9% of patients with early GC, 24.0% of patients with advanced GC, and 6.7% of node-negative patients using H&E staining. Tumor size (odds ratio [OR], 1.509; 95% confidence interval [CI], 1.159-1.965; P < .01), differentiated type (OR, 1.817; 95% CI, 1.377-2.398; P < .001), and the depth of tumor invasion (OR, 3.011; 95% CI, 2.174-4.171; P < .001) were independent predictive factors for LVI. LVI-positive patients have a poorer prognosis than LVI-negative patients, irrespective of tumor stage or lymph node metastasis. LVI was an independent prognostic factor for patients with GC (hazard ratio, 1.299; 95% CI, 1.112-1.518; P < .001)., Conclusions: LVI provided additional prognostic information for GC patients, and LVI-positive patients should be considered candidates for adjuvant chemotherapy., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2020
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38. A positive feedback self-regulatory loop between miR-210 and HIF-1α mediated by CPEB2 is involved in trophoblast syncytialization: implication of trophoblast malfunction in preeclampsia†.
- Author
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Wang H, Zhao Y, Luo R, Bian X, Wang Y, Shao X, Li YX, Liu M, and Wang YL
- Subjects
- Cell Line, Chorionic Villi metabolism, Down-Regulation, Female, Humans, Phosphorylation, Pregnancy, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, MicroRNAs metabolism, Placenta metabolism, Pre-Eclampsia metabolism, RNA-Binding Proteins metabolism, Trophoblasts metabolism
- Abstract
The pregnancy complication preeclampsia is directly associated with hypoxic stress and insufficient trophoblast cell differentiation. The hypoxia-inducible microRNA (miRNA), miR-210, has been identified as a significantly up-regulated miRNA in preeclamptic placenta, and evidence in other cell types has indicated a feedback regulation between miR-210 and hypoxia-inducible factor-1α (HIF-1α) under hypoxic condition. It remains unclear whether and how the feedback loop between miR-210 and HIF-1α may contribute to trophoblast dysfunction in preeclampsia. Here, we proved that cytoplasmic polyadenylation element-binding 2 (CPEB2) was a direct target of miR-210 in human trophoblast. CPEB2 could inhibit the translation of hypoxia-induced HIF-1α via directly binding the cytoplasmic polyadenylation element (CPE) site in the 3'-untranslated region (UTR) of HIF-1α mRNA. The increase in the HIF-1α level upon hypoxia treatment could be efficiently reversed by miR-210 inhibitor. In addition, CPEB2 was primarily expressed in villous syncytiotrophoblasts, and the suppression of trophoblast cell syncytialization by miR-210 could be significantly rescued by CPEB2 overexpression. In preeclamptic placenta, the expression of CPEB2 was evidently lower than normal pregnant control, and the miR-210 level was aberrantly higher and trophoblast syncytialization was limited. The findings revealed a positive feedback loop between miR-210 and HIF-1α that is mediated by CPEB2 in human trophoblasts, and demonstrated a mechanism underlying the insufficient trophoblast syncytialization in preeclampsia under hypoxic stress., (© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2020
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39. Dynamical important residue network (DIRN): network inference via conformational change.
- Author
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Li Q, Luo R, and Chen HF
- Subjects
- Protein Conformation, Protein Interaction Maps, Proteins, Molecular Dynamics Simulation
- Abstract
Motivation: Protein residue interaction network has emerged as a useful strategy to understand the complex relationship between protein structures and functions and how functions are regulated. In a residue interaction network, every residue is used to define a network node, adding noises in network post-analysis and increasing computational burden. In addition, dynamical information is often necessary in deciphering biological functions., Results: We developed a robust and efficient protein residue interaction network method, termed dynamical important residue network, by combining both structural and dynamical information. A major departure from previous approaches is our attempt to identify important residues most important for functional regulation before a network is constructed, leading to a much simpler network with the important residues as its nodes. The important residues are identified by monitoring structural data from ensemble molecular dynamics simulations of proteins in different functional states. Our tests show that the new method performs well with overall higher sensitivity than existing approaches in identifying important residues and interactions in tested proteins, so it can be used in studies of protein functions to provide useful hypotheses in identifying key residues and interactions., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2019
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40. Plasma fractalkine levels are associated with renal inflammation and outcomes in immunoglobulin A nephropathy.
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Luo R, Guo SM, Li YQ, Yang Y, Li ML, Han M, He XF, Ge SW, and Xu G
- Subjects
- Adolescent, Adult, Animals, CX3C Chemokine Receptor 1 genetics, CX3C Chemokine Receptor 1 metabolism, Cells, Cultured, Female, Glomerulonephritis, IGA pathology, Humans, Inflammation blood, Inflammation etiology, Inflammation metabolism, Kidney Diseases blood, Kidney Diseases etiology, Kidney Diseases metabolism, Macrophages metabolism, Macrophages pathology, Male, Mesangial Cells metabolism, Mesangial Cells pathology, Mice, Middle Aged, Prognosis, Rats, Survival Rate, Young Adult, Biomarkers analysis, CX3C Chemokine Receptor 1 analysis, Glomerulonephritis, IGA complications, Inflammation diagnosis, Kidney Diseases diagnosis
- Abstract
Background: A recognized noninvasive biomarker to improve risk stratification of immunoglobulin A nephropathy (IgAN) patients is scarce. Fractalkine has been shown to play a key role in glomerular disease as chemoattractant, adhesion and even fibrosis factor. The current study assessed the possibility of plasma fractalkine as a novel biomarker in IgAN patients., Methods: Plasma fractalkine was measured in 229 patients with renal biopsy consistent IgAN from 2012 to 2014, and clinical, pathological and prognostic relationships were analyzed., Results: The plasma fractalkine levels in IgAN patients were significantly correlated with the creatinine level and 24-h urine protein by both univariate and multivariate analysis. Mesangial hypercellularity was still significantly correlated with the plasma fractalkine levels even after adjustment for other potential predictor variables by multivariate analysis. In addition, the counts of CD20+ B cells or CD68+ macrophage in renal biopsies of IgAN patients were significantly correlated with the plasma fractalkine levels, but not CD4+ and CD8+ T cells. Finally, we concluded that patients with higher plasma fractalkine levels had higher risk of poor renal outcome compared with those with lower plasma fractalkine levels. No association was observed between the CX3CR1 polymorphisms and clinical parameters including plasma fractalkine levels and prognosis. Recombinant fractalkine induced mesangial cells extracellular matrix synthesis and promoted the migration of microphage cells RAW264.7., Conclusions: Plasma fractalkine levels were associated with creatinine level, 24-h urine protein, mesangial hypercellularity pathological damage, the CD68+ macrophage and CD20+ B cell infiltration in renal tissue and renal outcome in IgAN patients. Plasma fractalkine might be a potential prognosis novel predictor in Chinese patients with IgAN., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
- Published
- 2019
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41. Epigenetic regulation of sulfur homeostasis in plants.
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Huang XY, Li M, Luo R, Zhao FJ, and Salt DE
- Subjects
- DNA Methylation, Gene Expression Regulation, Plant, Histones genetics, Histones metabolism, Homeostasis, Plant Proteins genetics, Plant Proteins metabolism, Plants genetics, Sulfur metabolism, Epigenesis, Genetic, Plants metabolism
- Abstract
Plants have evolved sophisticated mechanisms for adaptation to fluctuating availability of nutrients in soil. Such mechanisms are of importance for plants to maintain homeostasis of nutrient elements for their development and growth. The molecular mechanisms controlling the homeostasis of nutrient elements at the genetic level have been gradually revealed, including the identification of regulatory factors and transporters responding to nutrient stresses. Recent studies have suggested that such responses are controlled not only by genetic regulation but also by epigenetic regulation. In this review, we present recent studies on the involvement of DNA methylation, histone modifications, and non-coding RNA-mediated gene silencing in the regulation of sulfur homeostasis and the response to sulfur deficiency. We also discuss the potential effect of sulfur-containing metabolites such as S-adenosylmethionine on the maintenance of DNA and histone methylation., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2019
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42. CT-based radiomic signatures for prediction of pathologic complete response in esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy.
- Author
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Yang Z, He B, Zhuang X, Gao X, Wang D, Li M, Lin Z, and Luo R
- Subjects
- Adult, Aged, Esophageal Neoplasms diagnostic imaging, Esophageal Squamous Cell Carcinoma diagnostic imaging, Female, Humans, Logistic Models, Male, Middle Aged, ROC Curve, Regression Analysis, Retrospective Studies, Tomography, X-Ray Computed, Treatment Outcome, Chemoradiotherapy, Adjuvant, Esophageal Neoplasms drug therapy, Esophageal Neoplasms radiotherapy, Esophageal Squamous Cell Carcinoma drug therapy, Esophageal Squamous Cell Carcinoma radiotherapy
- Abstract
The objective of this study was to build models to predict complete pathologic response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in esophageal squamous cell carcinoma (ESCC) patients using radiomic features. A total of 55 consecutive patients pathologically diagnosed as having ESCC were included in this study. Patients were divided into a training cohort (44 patients) and a testing cohort (11 patients). The logistic regression analysis using likelihood ratio forward selection was performed to select the predictive clinical parameters for pCR, and the least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomic predictors in the training cohort. Model performance in the training and testing groups was evaluated using the area under the receiver operating characteristic curves (AUC). The multivariate logistic regression analysis identified no clinical predictors for pCR. Thus, only radiomic features selected by LASSO were used to build prediction models. Three logistic regression models for pCR prediction were developed in the training cohort, and they were able to predict pCR well in both the training (AUC, 0.84-0.86) and the testing cohorts (AUC, 0.71-0.79). There were no differences between these AUCs. We developed three predictive models for pCR after nCRT using radiomic parameters and they demonstrated good model performance., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)
- Published
- 2019
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43. Tissue Transglutaminase-Mediated AT1 Receptor Sensitization Underlies Pro-inflammatory Cytokine LIGHT-Induced Hypertension.
- Author
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Liu C, Luo R, Wang W, Peng Z, Johnson GVW, Kellems RE, and Xia Y
- Subjects
- Animals, Disease Models, Animal, Female, Hypertension etiology, Hypertension physiopathology, Inflammation complications, Kidney metabolism, Male, Mice, Mice, Transgenic, Protein Glutamine gamma Glutamyltransferase 2, Receptor, Angiotensin, Type 1 metabolism, Tumor Necrosis Factor Ligand Superfamily Member 14 toxicity, Blood Pressure physiology, GTP-Binding Proteins metabolism, Hypertension metabolism, Inflammation metabolism, Transglutaminases metabolism
- Abstract
Background: Although numerous recent studies have shown a strong link between inflammation and hypertension, the underlying mechanisms by which inflammatory cytokines induce hypertension remain to be fully elucidated. Hypertensive disorders are also associated with elevated pressor sensitivity. Tissue transglutaminase (TG2), a potent cross-linking enzyme, is known to be transcriptionally activated by inflammatory cytokines and stabilize angiotensin II (Ang II) receptor AT1 (AT1R) via ubiquitination-preventing posttranslational modification. Here we sought to investigate the TG2-mediated AT1R stabilization in inflammation-induced hypertension and its functional consequences with a focus on receptor abundance and Ang II responsiveness., Methods and Results: Using an experimental model of inflammation-induced hypertension established by introducing the pro-inflammatory tumor necrosis factor cytokine LIGHT, we provide pharmacologic and genetic evidence that TG2 is required for LIGHT-induced hypertension (systolic pressure on day 6: LIGHT = 152.3 ± 7.4 vs. LIGHT+ERW1041E [TG2 inhibitor] = 105.8 ± 13.1 or LIGHT+TG2-/- = 114.3 ± 4.3 mm Hg, P < 0.05, n = 4-5) and renal compromise (urine albumin/creatinine: LIGHT = 0.17 ± 0.05 vs. LIGHT+ERW1041E = 0.03 ± 0.01 or LIGHT+TG2-/- = 0.06 ± 0.01 mg/mg; plasma creatinine: LIGHT = 1.11 ± 0.04 vs. LIGHT+ERW1041E = 0.94 ± 0.04 or LIGHT+TG2-/- = 0.88 ± 0.09 mg/dl; urine volume: LIGHT = 0.23 ± 0.1 vs. LIGHT+ERW1041E = 0.84 ± 0.13 or LIGHT+TG2-/- = 1.02 ± 0.09 ml/24 hour on day 14, P < 0.05, n = 4-5). Our mechanistic studies showed that the TG2-mediated AT1R modification and accumulation (relative renal AT1R level: phosphate-buffered saline [PBS] = 1.23 ± 0.22, LIGHT = 3.49 ± 0.37, and LIGHT+ERW1041E = 1.77 ± 0.46, P < 0.05, n = 3; LIGHT+TG2+/+ = 85.28 ± 36.11 vs. LIGHT+TG2-/- = 7.01 ± 5.68, P < 0.05, n = 3) induced by LIGHT is associated with abrogated β-arrestin binding (AT1R/associated β-arrestin ratio: PBS = 2.62 ± 1.07, LIGHT = 38.60 ± 13.91, and LIGHT+ERW1041E = 6.97 ± 2.91, P < 0.05, n = 3; LIGHT+TG2+/+ = 66.43 ± 44.81 vs. LIGHT+TG2-/- = 2.45 ± 1.78, P < 0.01, n = 3) and could be found in renal medulla tubules of kidneys (relative tubular AT1R level: PBS = 5.91 ± 2.93, LIGHT = 92.82 ± 19.54, LIGHT+ERW1041E = 28.49 ± 11.65, and LIGHT+TG2-/- = 0.14 ± 0.10, P < 0.01, n = 5) and the blood vasculature (relative vascular AT1R level: PBS = 0.70 ± 0.30, LIGHT = 13.75 ± 2.49, and LIGHT+ERW1041E = 3.28 ± 0.87, P < 0.01, n = 3), 2 of the tissues highly related to the genesis of hypertension. Our in vitro cellular assays showed that LIGHT stimulation triggered a rapid TG2-dependent increase in the abundance of AT1Rs (relative AT1R level after 2-hour LIGHT treatment: AT1R (WT)+TG2 = 2.21 ± 0.23, AT1R (Q315A)+TG2 = 0.18 ± 0.23, P < 0.05 vs. starting point = 1, n = 2) and downstream calcium signaling (fold increase in NFAT-driven luciferase activity: Saline = 0.02 ± 0.03, Ang II = 0.17 ± 0.08, LIGHT = 0.05 ± 0.04, LIGHT+Ang II = 0.90 ± 0.04 (P < 0.01 vs. Ang II), and LIGHT+Ang II+ERW1041E = 0.15 ± 0.15 (P < 0.01 vs. LIGHT+Ang II), n = 3)., Conclusions: Our data indicate an essential and systemic role for TG2 in bridging inflammation to hypertension via its posttranslational modifications stabilizing AT1 receptor and sensitizing Ang II. Our findings also suggest that TG2 inhibitors could be used as a novel group of cardiovascular agents., (© The Author(s) 2019. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)
- Published
- 2019
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44. AC-DIAMOND v1: accelerating large-scale DNA-protein alignment.
- Author
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Mai H, Zhang Y, Li D, Leung HC, Luo R, Wong CK, Ting HF, and Lam TW
- Subjects
- DNA, Databases, Protein, Proteins, Sequence Analysis, DNA, Software
- Abstract
Summary: AC-DIAMOND (v1) is a DNA-protein alignment tool designed to tackle the efficiency challenge of aligning large amount of reads or contigs to protein databases. When compared with the previously most efficient method DIAMOND, AC-DIAMOND gains a 6- to 7-fold speed-up, while retaining a similar degree of sensitivity. The improvement is rooted at two aspects: first, using a compressed index of seeds with adaptive-length to speed-up the matching between query and reference sequences; second, adopting a compact form of dynamic programing to fully utilize the parallelism of the SIMD capability., Availability and Implementation: Software source codes and binaries available at https://github.com/Maihj/AC-DIAMOND/., Supplementary Information: Supplementary data are available at Bioinformatics online.
- Published
- 2018
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45. First Draft Genome Sequence of the Pathogenic Fungus Lomentospora prolificans (Formerly Scedosporium prolificans ).
- Author
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Luo R, Zimin A, Workman R, Fan Y, Pertea G, Grossman N, Wear MP, Jia B, Miller H, Casadevall A, Timp W, Zhang SX, and Salzberg SL
- Subjects
- Fungal Proteins genetics, Whole Genome Sequencing, Genome, Fungal, Molecular Sequence Annotation, Scedosporium genetics
- Abstract
Here we describe the sequencing and assembly of the pathogenic fungus Lomentospora prolificans using a combination of short, highly accurate Illumina reads and additional coverage in very long Oxford Nanopore reads. The resulting assembly is highly contiguous, containing a total of 37,627,092 bp with over 98% of the sequence in just 26 scaffolds. Annotation identified 8896 protein-coding genes. Pulsed-field gel analysis suggests that this organism contains at least 7 and possibly 11 chromosomes, the two longest of which have sizes corresponding closely to the sizes of the longest scaffolds, at 6.6 and 5.7 Mb., (Copyright © 2017 Luo et al.)
- Published
- 2017
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46. 16GT: a fast and sensitive variant caller using a 16-genotype probabilistic model.
- Author
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Luo R, Schatz MC, and Salzberg SL
- Subjects
- Animals, Genome-Wide Association Study standards, Haplotypes, Humans, Models, Genetic, Polymorphism, Single Nucleotide, Probability, Sensitivity and Specificity, Exome Sequencing standards, Genome-Wide Association Study methods, Genotype, Software, Exome Sequencing methods
- Abstract
16GT is a variant caller for Illumina whole-genome and whole-exome sequencing data. It uses a new 16-genotype probabilistic model to unify single nucleotide polymorphism and insertion and deletion calling in a single variant calling algorithm. In benchmark comparisons with 5 other widely used variant callers on a modern 36-core server, 16GT demonstrated improved sensitivity in calling single nucleotide polymorphisms, and it provided comparable sensitivity and accuracy for calling insertions and deletions as compared to the GATK HaplotypeCaller. 16GT is available at https://github.com/aquaskyline/16GT., (© The Authors 2017. Published by Oxford University Press.)
- Published
- 2017
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47. Hospitalized burden and outcomes of coccidioidomycosis: A nationwide analysis, 2005-2012.
- Author
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Luo R, Greenberg A, and Stone CD
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Coccidioidomycosis mortality, Female, Humans, Incidence, Length of Stay, Male, Middle Aged, Retrospective Studies, Survival Analysis, Treatment Outcome, United States epidemiology, Young Adult, Coccidioidomycosis drug therapy, Coccidioidomycosis epidemiology, Hospitalization
- Abstract
The incidence of coccidioidomycosis (CM) infection has increased over the last 20 years. We investigated recent trends of CM-associated hospitalization in the United States. patients with CM-associated hospitalization were identified from the Nationwide Inpatient Sample, 2005-2012. The outcomes of interest were the trend of annual hospitalization, in-hospital mortality, and independent risk factors for mortality. A total of 30,870 hospitalizations with CM (29,584 of adults; 1,286 of children) were identified. Over the 8-year study period, the number of hospitalizations for CM fluctuated but increased overall with successively higher peaks in 2009 and 2011. The annual median length of stay (LOS) shortened from 6 to 7 days in 2005-2010 to 4 days in 2011 and 5 days in 2012. The inflation-adjusted hospital charges were highest in 2006 then trended down by 21% in 2012. The in-hospital mortality declined from the highest level in 2005 (5.2%) to a low in 2010 (1.1%), then increased modestly in 2011 (1.9%) and 2012 (1.5%). Hospitalizations were identified in 46 states, with nearly half in Arizona (49.1%), followed by California (36.8%), Texas (3.3%), and Nevada (1.6%). Logistic regression analysis in adults revealed that in-hospital mortality was associated with age groups 61-70 years and >70 years (OR = 3.3 and 3.5, respectively. Ref: 18-30 years) and Charlson Index ≥1 (OR = 2.0-8.3). In children, males had lower risk for mortality than females (OR = 0.2). This study shows that CM-associated hospitalizations occur widely throughout the United States with an increasing admission trend; however, patient outcomes have improved and the cost of hospitalization has decreased., (© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2017
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48. Nomogram for radiation-induced hypothyroidism prediction in nasopharyngeal carcinoma after treatment.
- Author
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Luo R, Li M, Yang Z, Zhan Y, Huang B, Lu J, Xu Z, and Lin Z
- Subjects
- Adolescent, Adult, Aged, Carcinoma, Female, Follow-Up Studies, Humans, Male, Middle Aged, Nasopharyngeal Carcinoma, Proportional Hazards Models, Prospective Studies, Radiation Dosage, Sex Distribution, Thyroid Gland radiation effects, Young Adult, Hypothyroidism etiology, Nasopharyngeal Neoplasms radiotherapy, Nomograms, Radiation Injuries diagnosis, Radiotherapy adverse effects
- Abstract
Objective: The aim of this study was to develop a nomogram for radiation-induced hypothyroidism (RHT) prediction., Methods: We collected data from 164 patients with nasopharyngeal carcinoma (NPC) in our previous prospective study. Biochemical hypothyroidism was defined as a serum thyroid-stimulating hormone level greater than the normal value. We collected both clinical and dose-volume factors. A univariate Cox regression analysis was performed to identify RHT risk factors. Optimal predictors were selected according to the least absolute shrinkage and selection operator (LASSO). We then selected the Cox regression models that best balanced the prediction performance and practicability to build a nomogram for RHT prediction., Results: There were 38 (23.2%) patients who developed RHT, and the median follow-up was 24 months. The univariate Cox regression analysis indicated that gender, minimum dose, mean dose (D
mean ) and V25 -V60 [Vx (%), the percentage of thyroid volume receiving >x Gy] of the thyroid were significantly associated with RHT. The variables of gender, receiving chemotherapy or not (chemo), Dmean and V50 were selected using the LASSO analysis. A nomogram based on a three-variable (gender, chemo and V50 ) Cox regression model was constructed, and its concordance index was 0.72. Good accordance between prediction and observation was showed by calibration curves in the probability of RHT at 18, 24 and 30 months., Conclusion: This study built a nomogram for RHT in NPC survivors by analyzing both clinical and dose-volume parameters using LASSO. Thus, the individual dose constraint could be achieved in a visual format. Advances in knowledge: This study used LASSO to more accurately address the multicollinear problem between variables. The resulting nomogram will help physicians predict RHT.- Published
- 2017
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49. Single-Dose Study of a Corticotropin-Releasing Factor Receptor-1 Antagonist in Women With 21-Hydroxylase Deficiency.
- Author
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Turcu AF, Spencer-Segal JL, Farber RH, Luo R, Grigoriadis DE, Ramm CA, Madrigal D, Muth T, O'Brien CF, and Auchus RJ
- Subjects
- 17-alpha-Hydroxyprogesterone blood, Adrenal Hyperplasia, Congenital metabolism, Adrenocorticotropic Hormone blood, Adult, Azabicyclo Compounds adverse effects, Azabicyclo Compounds pharmacokinetics, Dose-Response Relationship, Drug, Female, Humans, Middle Aged, Oxadiazoles adverse effects, Oxadiazoles pharmacokinetics, Time Factors, Young Adult, Adrenal Hyperplasia, Congenital drug therapy, Azabicyclo Compounds administration & dosage, Oxadiazoles administration & dosage, Receptors, Corticotropin-Releasing Hormone antagonists & inhibitors
- Abstract
Context: Treatment of 21-hydroxylase deficiency (21OHD) is difficult to optimize. Normalization of excessive ACTH and adrenal steroid production commonly requires supraphysiologic doses of glucocorticoids., Objectives: We evaluated the safety and tolerability of the selective corticotropin releasing factor type 1 (CRF1) receptor antagonist NBI-77860 in women with classic 21OHD and tested the hypothesis that CRF1 receptor blockade decreases early-morning ACTH and 17α-hydroxyprogesterone (17OHP) in these patients., Participants: The study enrolled eight classic 21OHD females, ages 18-58 years, seen at a single tertiary referral university setting., Design: This was a phase Ib, single-blind, placebo-controlled, fixed-sequence, single-dose trial. During three treatment periods separated by 3-week washout intervals, patients sequentially received placebo, NBI-77860 300 mg, and NBI-77860 600 mg at 10 pm; glucocorticoid therapy was withheld for 20 hours. We evaluated ACTH, 17OHP, androstenedione, and testosterone as well as NBI-77860 pharmacokinetics over 24 hours., Results: Dose-dependent reductions of ACTH and/or 17OHP were observed in six of eight subjects. Relative to placebo, NBI-77860 led to an ACTH and 17OHP reduction by a mean of 43% and 0.7% for the 300 mg dose, respectively, and by 41% and 27% for the 600 mg dose, respectively. Both NBI-77860 doses were well tolerated., Conclusion: The meaningful reductions in ACTH and 17OHP following NBI-77860 dosing in 21OHD patients demonstrate target engagement and proof of principle in this disorder. These promising data provide a rationale for additional investigations of CRF1 receptor antagonists added to physiologic doses of hydrocortisone and fludrocortisone acetate for the treatment of classic 21OHD.
- Published
- 2016
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50. database.bio: a web application for interpreting human variations.
- Author
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Ou M, Ma R, Cheung J, Lo K, Yee P, Luo T, Chan TL, Au CH, Kwong A, Luo R, and Lam TW
- Subjects
- High-Throughput Nucleotide Sequencing, Humans, Internet, Molecular Sequence Annotation, Databases, Nucleic Acid, Genetic Variation, Software
- Abstract
Unlabelled: Rapid advances of next-generation sequencing technology have led to the integration of genetic information with clinical care. Genetic basis of diseases and response to drugs provide new ways of disease diagnosis and safer drug usage. This integration reveals the urgent need for effective and accurate tools to analyze genetic variants. Due to the number and diversity of sources for annotation, automating variant analysis is a challenging task. Here, we present database.bio, a web application that combines variant annotation, prioritization and visualization so as to support insight into the individual genetic characteristics. It enhances annotation speed by preprocessing data on a supercomputer, and reduces database space via a unified database representation with compressed fields., Availability and Implementation: Freely available at https://database.bio., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
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