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Spatial transcriptomics (ST) has emerged as a powerful tool for unravelling tissue structure and function. However, the continuous development of ST has made it challenging to select and effectively use appropriate analysis tools. To address this issue, we have developed the Spatial Transcriptome Analysis Hub (STASH,http://cailab.labshare.cn:7004), a comprehensive, systematic, and user-friendly database of ST analysis tools. STASH collects and categorizes most of the tools currently available and provides insight into their current status and trends. This can help researchers quickly locate the appropriate tool for their needs, or even guide researchers in the development of better tools.

Understanding how long noncoding RNAs (lncRNAs) cooperate with splicing factors (SFs) in alternative splicing (AS) control is fundamental to human biology and disease. We show that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-documented AS-implicated lncRNA, regulates AS via two SFs, polypyrimidine tract–binding protein 1 (PTBP1) and PTB-associated SF (PSF). MALAT1 stabilizes the interaction between PTBP1 and PSF, thereby forming a functional module that affects a network of AS events. The MALAT1-stabilized PTBP1/PSF interaction occurs in multiple cellular contexts; however, the functional module, relative to MALAT1 only, has more dominant pathological significance in hepatocellular carcinoma. MALAT1 also stabilizes the PSF interaction with several heterogeneous nuclear ribonucleoparticle proteins other than PTBP1, hinting a broad role in AS control. We present a model in which MALAT1 cooperates with distinct SFs for AS regulation and pose that, relative to analyses exclusively performed for lncRNAs, a comprehensive consideration of lncRNAs and their binding partners may provide more information about their biological functions.

Cervical cancer is a heterogeneous malignancy mainly caused by human papillomavirus (HPV). While a few studies have revealed heterogeneity of cervical cancer in chromosome levels, the correlation between genetic heterogeneity and HPV integration in cervical cancer remains unknown. Here, we applied multi-region whole-exome sequencing (WES) and HPV integration analysis to explore intratumor heterogeneity (ITH) in cervical cancer. We sequenced 20 tumor regions and 5 adjacent normal tissues from 5 cervical cancer patients, analysis based on somatic mutations and somatic copy number alterations (SCNAs) levels were performed. Variable heterogeneity was observed between the five patients with different tumor stages and HPV infection statuses. We found HPV integration has a positive effect on somatic mutation burden, but the relation to SCNAs remains unclear. Frequently mutated genes in cervical cancer were identified as trunk events, such as FBXW7, PIK3CA, FAT1 in somatic mutations and TP63, MECOM, PIK3CA, TBL1XR1 in SCNAs. New potential driver genes in cervical cancer were summarized including POU2F2, TCF7 and UBE2A. The SCNAs level has potential relation with tumor stage, and Signature 3 related to homologous recombination deficiency (HRD) may be the appropriate biomarker in advanced cervical cancer. Mutation signature analysis also revealed a potential pattern that APOBEC-associated signature occurs in early-stage and signatures associated with DNA damage repair arise at the later stage of cervical cancer evolution. In a conclusion, our study provides insights into the potential relationship between HPV infection and tumor heterogeneity. Those results enhanced our understanding of tumorigenesis and progression in cervical cancer.

Mammalian teeth develop from the inductive epithelial-mesenchymal interaction, an important mechanism shared by many organs. The cellular basis for such interaction remains elusive. Here, we generate a dual-fluorescence model to track and analyze dental cells from embryonic to postnatal stages, in which Pitx2

A numerical calculation model is developed to study the coupled thermal dynamic performance in a cryogenic fuel tank under an intermittent sloshing excitation. Both external heat inputs and the intermittent excitation are realized by User-defined functions. The volume of fluid method is adopted to simulate fluid sloshing, coupled with the mesh motion treatment. Validated against related fluid sloshing experiments, the numerical model was turned out to be acceptable on fluid sloshing prediction. Cooled by subcooled liquid, vapor is always in condensation. The middle vapor pressure test point suffers less from the intermittent excitation and has a linear pressure decrease profile, while the middle liquid pressure test point has fluctuating variations. For vapor and interface temperature monitors, obvious temperature fluctuations appear in the second holding period. While for liquid test points, the temperature profiles experience intensive fluctuations during sloshing periods and stable temperature variation during holding periods. Due to the holding period of external excitation, the tank pressure reduction in intermittent sloshing case is less than that in continuous sloshing case. That is to say the tank pressure decrease rate could be adjusted by proper intermittent excitation. This work is significant to deeply understand fluid sloshing phenomenon under some irregular external excitations in fuel storage tanks.

BRCA1 mutation is the genetic predisposition in causing genome instability towards cancer. BRCA1 mutation is predominantly germline inherited at the fertilization. However, when the inherited mutation initiates genome instability in the mutation carriers remains largely elusive. We used a heterozygotic Brca1-knockout mouse as a model to investigate the issue. Through whole-genome sequencing and bioinformatics analysis, we monitored genome status across the developmental stages from embryo to adulthood in the mouse model. We observed that genome instability as reflected by structural variation, indel and copy number variation already appeared at 10.5-day embryo and progressively towards adulthood. We also observed that the genome instability was not linearly accumulated but dynamically changed along the developmental process, affecting many oncogenic genes and pathways including DNA damage repair, estrogen signaling, and oncogenesis. We further observed that many genome abnormalities in the cancer caused by Brca1 mutation were originated at embryonic stage, and Trp53 (TP53) mutation was not essential for the Brca1 mutation-caused genome instability in the non-cancer cells. Our study revealed that heterozygotic Brca1 mutation alone can cause genome instability at embryonic stage, highlighting that prevention of BRCA1 mutation-related cancer in humans may need to start earlier than currently considered.

Real-time quantitative PCR is currently the most widely used method for the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identification. Due to the rapid evolution of the SARS-CoV-2 genome, novel mutations on the primer binding sites will cause the failure of PCR. Therefore, in addition to a well-designed primer set, these primers need to be updated and evaluated regularly to ensure that the rapidly evolving genome primers can be amplified. In this protocol, (1) we firstly use assembled genome sequences in the SARS-CoV-2 database to identify and characterize indels and point mutations; (2) design primers skipping the sites of mutations; (3) check the coverage of the primers with the daily update SARS-CoV-2 database; (4) redesign them if novel mutations found in the primer binding sites. Although this protocol takes SARS-CoV-2 as an example, it is suitable for other species that have genomes accumulating mutations over time.

Real-time quantitative PCR is currently the most widely used method for the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identification. Due to the rapid evolution of the SARS-CoV-2 genome, novel mutations on the primer binding sites will cause the failure of PCR. Therefore, in addition to a well-designed primer set, these primers need to be updated and evaluated regularly to ensure that the rapidly evolving genome primers can be amplified. In this protocol, (1) we firstly use assembled genome sequences in the SARS-CoV-2 database to identify and characterize indels and point mutations; (2) design primers skipping the sites of mutations; (3) check the coverage of the primers with the daily update SARS-CoV-2 database; (4) redesign them if novel mutations found in the primer binding sites. Although this protocol takes SARS-CoV-2 as an example, it is suitable for other species that have genomes accumulating mutations over time.

Quality control (QC) for lab-designed primers is crucial for the success of a polymerase chain reaction (PCR). Here, we present MFEprimer-3.0, a functional primer quality control program for checking non-specific amplicons, dimers, hairpins and other parameters. The new features of the current version include: (i) more sensitive binding site search using the updated k-mer algorithm that allows mismatches within the k-mer, except for the first base at the 3′ end. The binding sites of each primer with a stable 3′ end are listed in the output; (ii) new algorithms for rapidly identifying self-dimers, cross-dimers and hairpins; (iii) the command-line version, which has an added option of JSON output to enhance the versatility of MFEprimer by acting as a QC step in the ‘primer design → quality control → redesign’ pipeline; (iv) a function for checking whether the binding sites contain single nucleotide polymorphisms (SNPs), which will affect the consistency of binding efficiency among different samples. In summary, MFEprimer-3.0 is updated with the well-tested PCR primer QC program and it can be integrated into various PCR primer design applications as a QC module. The MFEprimer-3.0 server is freely accessible without any login requirement at: https://mfeprimer3.igenetech.com/ and https://www.mfeprimer.com/. The source code for the command-line version is available upon request.

Autophagy is a highly evolutionarily conserved cellular catabolic process responsible for degradation of damaged organelles and long-lived proteins. It is not surprising that scientific interest in the connection of autophagy and diseases has been growing. Over the past 2 decades, many new experimental approaches have been emerging in the field of targeting autophagy for medicinal research. Interestingly, in addition to experimental methods, a number of databases, Web servers, mathematics models, omics approaches, and systems biology network approaches related to autophagy have become available online, which may be collectively considered to be "in silico autophagy methods" for expediting current medicinal research. Thus, we have summarized a series of relevant in silico autophagy approaches for promoting the most appropriate usage of these resources for potential therapeutic purposes.

Background Postmastectomy radiation (PMRT) is an important adjuvant treatment for high-risk breast cancer. However, evidence concerning its efficacy in promoting survival of patients with 1–3 positive axillary lymph nodes remains insufficient. Methods We identified 57,793 patients, diagnosed from 2010–2015, from the Surveillance, Epidemiology, and End Results database, including 15,126 cases treated with beam radiation and 42,667 cases with none/unknown radiation. A Kaplan–Meier curve was utilized to compare survival of the two groups. We used univariate and multivariate Cox proportional hazard models to identify independent prognostic factors presented as hazard ratios (HRs) and 95% confidence intervals (CIs). For subgroup analysis, patients were stratified according to lymph node status, tumor size, and molecular subtypes. Results The PMRT group showed more aggressive clinicopathological features, including higher grades (P

Background The yak is a species of livestock which is crucial for local communities of the Qinghai-Tibet Plateau and adjacent regions and naturally owns one more thoracic vertebra than cattle. Recently, a sub-population of yak termed as the Jinchuan yak has been identified with over half its members own a thoracolumbar vertebral formula of T15L5 instead of the natural T14L5 arrangement. The novel T15L5 positioning is a preferred genetic trait leading to enhanced meat and milk production. Selective breeding of this trait would have great agricultural value and exploration of the molecular mechanisms underlying this trait would both accelerate this process and provide us insight into the development and regulation of somitogenesis. Results Here we investigated the genetic background of the Jinchuan yak through resequencing fifteen individuals, comprising five T15L5 individuals and ten T14L5 individuals with an average sequencing depth of > 10X, whose thoracolumbar vertebral formulae were confirmed by anatomical observation. Principal component analysis, linkage disequilibrium analysis, phylogenetic analysis, and selective sweep analysis were carried out to explore Jinchuan yak’s genetic background. Three hundred and thirty candidate markers were identified as associated with the additional thoracic vertebrae and target sequencing was used to validate seven carefully selected markers in an additional 51 Jinchuan yaks. The accuracies of predicting 15 thoracic vertebrae and 20 thoracolumbar vertebrae with these 7 markers were 100.00 and 33.33% despite they both could only represent 20% of all possible genetic diversity. Two genes, PPP2R2B and TBLR1, were found to harbour the most candidate markers associated with the trait and likely contribute to the unique somitic number and identity according to their reported roles in the mechanism of somitogenesis. Conclusions Our findings provide a clear depiction of the Jinchuan yak’s genetic background and a solid foundation for marker-assistant selection. Further exploitation of this unique population and trait could be promoted with the aid of our genomic resource.

Triple‑negative breast cancer (TNBC) accounts for ~15% of all breast cancer diagnoses each year. Patients with TNBC tend to have a higher risk for early relapse and a worse prognosis. TNBC is characterized by extensive somatic copy number alterations (CNAs). However, the DNA CNA profile of TNBC remains to be extensively investigated. The present study assessed the genomic profile of CNAs in 201 TNBC samples, aiming to identify recurrent CNAs that may drive the pathogenesis of TNBC. In total, 123 regions of significant amplification and deletion were detected using the Genomic Identification of Significant Targets in Cancer algorithm, and potential driver genes for TNBC were identified. A total of 31 samples exhibited signs of chromothripsis and revealed chromosome pulverization hotspot regions. The present study further determined 199 genomic locations that were significantly enriched for breakpoints, which indicated TNBC‑specific genomic instability regions. Unsupervised hierarchical clustering of tumors resulted in three main subgroups that exhibited distinct CNA profiles, which may reveal the heterogeneity of molecular mechanisms in TNBC subgroups. These results will extend the molecular understanding of TNBC and will facilitate the discovery of therapeutic and diagnostic target candidates.

Comprehensive genomic analyses of cancers have revealed substantial intrapatient molecular heterogeneities that may explain some instances of drug resistance and treatment failures. Examination of the clonal composition of an individual tumor and its evolution through disease progression and treatment may enable identification of precise therapeutic targets for drug design. Multi-region and single-cell sequencing are powerful tools that can be used to capture intratumor heterogeneity. Here, we present a database we’ve named CancerTracer (http://cailab.labshare.cn/cancertracer): a manually curated database designed to track and characterize the evolutionary trajectories of tumor growth in individual patients. We collected over 6000 tumor samples from 1548 patients corresponding to 45 different types of cancer. Patient-specific tumor phylogenetic trees were constructed based on somatic mutations or copy number alterations identified in multiple biopsies. Using the structured heterogeneity data, researchers can identify common driver events shared by all tumor regions, and the heterogeneous somatic events present in different regions of a tumor of interest. The database can also be used to investigate the phylogenetic relationships between primary and metastatic tumors. It is our hope that CancerTracer will significantly improve our understanding of the evolutionary histories of tumors, and may facilitate the identification of predictive biomarkers for personalized cancer therapies.

Supplemental Digital Content is available in the text, Cervical cancer is among the most frequent cancer types in women worldwide. Radiotherapy, including external beam radiation and brachytherapy, is one of the commonly used treatment options for cervical cancer. However, the adverse effects of radiation therapy on cervical cancer survival have been poorly investigated with inconclusive results. Therefore, the aim of this study was to determine the suitable radiotherapy modality according to patients’ characteristics. A retrospective survival analysis of 44,602 patients was performed using the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate proportional hazard Cox model was used to evaluate the prognostic impact of different radiotherapy modalities, primary surgery, age, TNM stage, and tumor size. Our results indicated that patients without primary surgery, diagnosed at older age (≥45 years’ old), at advanced TNM stages (III/IV) or with larger tumor size (≥3 cm) could benefit from radiotherapy. However, radiotherapy was detrimental in patients with primary surgery, diagnosed at younger age (

Autophagy is a highly evolutionarily conserved cellular catabolic process responsible for degradation of damaged organelles and long-lived proteins. It is not surprising that scientific interest in the connection of autophagy and diseases has been growing. Over the past 2 decades, many new experimental approaches have been emerging in the field of targeting autophagy for medicinal research. Interestingly, in addition to experimental methods, a number of databases, Web servers, mathematics models, omics approaches, and systems biology network approaches related to autophagy have become available online, which may be collectively considered to be "in silico autophagy methods" for expediting current medicinal research. Thus, we have summarized a series of relevant in silico autophagy approaches for promoting the most appropriate usage of these resources for potential therapeutic purposes.

Chromothripsis is a recently observed phenomenon in cancer cells in which one or several chromosomes shatter into pieces with subsequent inaccurate reassembly and clonal propagation. This type of event generates a potentially vast number of mutations within a relatively short-time period, and has been considered as a new paradigm in cancer development. Despite recent advances, much work is still required to better understand the molecular mechanisms of this phenomenon, and thus an easy-to-use tool is in urgent need for automatically detecting and annotating chromothripsis. Here we present CTLPScanner, a web server for detection of chromothripsis-like pattern (CTLP) in genomic array data. The output interface presents intuitive graphical representations of detected chromosome pulverization region, as well as detailed results in table format. CTLPScanner also provides additional information for associated genes in chromothripsis region to help identify the potential candidates involved in tumorigenesis. To assist in performing meta-data analysis, we integrated over 50 000 pre-processed genomic arrays from The Cancer Genome Atlas and Gene Expression Omnibus into CTLPScanner. The server allows users to explore the presence of chromothripsis signatures from public data resources, without carrying out any local data processing. CTLPScanner is freely available at http://cgma.scu.edu.cn/CTLPScanner/.

Xiao Zhang,1,* Jian Yang,2,* Haoyang Cai,2 Yifeng Ye1 1Department of Breast Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 611731, China; 2Center of Growth, Metabolism, and Aging, Key Laboratory of Bio-Resources and Eco-Environment, College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, China *These authors contributed equally to this work Objective: To compare the prognosis of young breast cancer patients with the older ones. Patients and methods: Utilizing the Surveillance, Epidemiology, and End Results database, we identified 150,588 female breast cancer patients diagnosed during 2003–2014, including 6,668 patients younger than 35 years and 143,920 patients aged between 35 and 60 years. Kaplan–Meier analysis was performed to compare the prognosis of these two groups. Univariate and multivariate Cox proportional hazard models were utilized to identify independent prognostic factors and calculate the HR and 95% CI. Subgroup analysis was performed stratified according to the lymph node status and estrogen receptor (ER) status. Results: The young patients presented with more aggressive clinicopathological characteristics, including larger tumor size (P

Accurate detection of chromothripsis event is important to study the mechanisms underlying this phenomenon. CTLPScanner ( http://cgma.scu.edu.cn/CTLPScanner/ ) is a web-based tool for identification and annotation of chromothripsis-like pattern (CTLP) in genomic array data. In this chapter, we illustrate the utility of CTLPScanner for screening chromosome pulverization regions and give interpretation of the results. The web interface offers a set of parameters and thresholds for customized screening. We also provide practical recommendations for effective chromothripsis detection. In addition to the user data processing module, CTLPScanner contains more than 50,000 preprocessed oncogenomic arrays, which allow users to explore the presence of chromothripsis signatures from public data resources.

ChromothripsisDB ( http://cgma.scu.edu.cn/ChromothripsisDB ) is a manually curated database containing a unified description of published chromothripsis cases and relevant genomic aberrations. Available data includes copy number alterations, chromosome structural variations, and gene annotations. The criteria used for detecting chromothripsis in each study are also provided. At present, the molecular mechanisms involved in chromothripsis phenomenon are not fully understood. Thus, further studies with large number of identified chromothripsis samples are needed. The current release of ChromothripsisDB contains more than 400 patient samples, representing over 100 research articles. It represents an extraordinary resource for mining the existing knowledge of chromothripsis.

Background The integration of DNA methylation and copy number alteration data promises to provide valuable insight into the underlying molecular mechanisms responsible for cancer initiation and progression. However, the generation and processing of these datasets are costly and time-consuming if carried out separately. The Illumina Infinium HumanMethylation450 BeadChip, initially designed for the evaluation of DNA methylation levels, allows copy number variant calling using bioinformatics tools. Results A substantial amount of Infinium HumanMethylation450 data across various cancer types has been accumulated in recent years and is a valuable resource for large-scale data analysis. Here we present MethCNA, a comprehensive database for genomic and epigenomic data integration in human cancer. In the current release, MethCNA contains about 10,000 tumor samples representing 37 cancer types. All raw array data were collected from The Cancer Genome Atlas and NCBI Gene Expression Omnibus database and analyzed using a pipeline that integrated multiple computational resources and tools. The normalized copy number aberration data and DNA methylation alterations were obtained. We provide a user-friendly web-interface for data mining and visualization. Conclusions The Illumina Infinium HumanMethylation450 BeadChip enables the interrogation and integration of both genomic and epigenomic data from exactly the same DNA specimen, and thus can aid in distinguishing driver from passenger mutations in cancer. We expect MethCNA will enable researchers to explore DNA methylation and copy number alteration patterns, identify key oncogenic drivers in cancer, and assist in the development of targeted therapies. MethCNA is publicly available online at http://cgma.scu.edu.cn/MethCNA. Electronic supplementary material The online version of this article (10.1186/s12864-018-4525-0) contains supplementary material, which is available to authorized users.