7 results on '"Luo, Minjie"'
Search Results
2. A highly sensitive and specific workflow for detecting rare copy-number variants from exome sequencing data.
- Author
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Rajagopalan, Ramakrishnan, Murrell, Jill R., Luo, Minjie, and Conlin, Laura K.
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FALSE positive error , *WORKFLOW , *FALSE discovery rate , *STOCHASTIC processes , *NUCLEOTIDE sequencing - Abstract
Background: Exome sequencing (ES) is a first-tier diagnostic test for many suspected Mendelian disorders. While it is routine to detect small sequence variants, it is not a standard practice in clinical settings to detect germline copy-number variants (CNVs) from ES data due to several reasons relating to performance. In this work, we comprehensively characterized one of the most sensitive ES-based CNV tools, ExomeDepth, against SNP array, a standard of care test in clinical settings to detect genome-wide CNVs. Methods: We propose a modified ExomeDepth workflow by excluding exons with low mappability prior to variant calling to drastically reduce the false positives originating from the repetitive regions of the genome, and an iterative variant calling framework to assess the reproducibility. We used a cohort of 307 individuals with clinical ES data and clinical SNP array to estimate the sensitivity and false discovery rate of the CNV detection using exome sequencing. Further, we performed targeted testing of the STRC gene in 1972 individuals. To reduce the number of variants for downstream analysis, we performed a large-scale iterative variant calling process with random control cohorts to assess the reproducibility of the CNVs. Results: The modified workflow presented in this paper reduced the number of total variants identified by one third while retaining a higher sensitivity of 97% and resulted in an improved false discovery rate of 11.4% compared to the default ExomeDepth pipeline. The exclusion of exons with low mappability removes 4.5% of the exons, including a subset of exons (0.6%) in disease-associated genes which are intractable by short-read next-generation sequencing (NGS). Results from the reproducibility analysis showed that the clinically reported variants were reproducible 100% of the time and that the modified workflow can be used to rank variants from high to low confidence. Targeted testing of 30 CNVs identified in STRC, a challenging gene to ascertain by NGS, showed a 100% validation rate. Conclusions: In summary, we introduced a modification to the default ExomeDepth workflow to reduce the false positives originating from the repetitive regions of the genome, created a large-scale iterative variant calling framework for reproducibility, and provided recommendations for implementation in clinical settings. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
3. Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma.
- Author
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Xu, Feng, Viaene, Angela N., Ruiz, Jenny, Schubert, Jeffrey, Wu, Jinhua, Chen, Jiani, Cao, Kajia, Fu, Weixuan, Bagatell, Rochelle, Fan, Zhiqian, Long, Ariel, Pagliaroli, Luca, Zhong, Yiming, Luo, Minjie, Kreiger, Portia A., Surrey, Lea F., Wertheim, Gerald B., Cole, Kristina A., Li, Marilyn M., and Santi, Mariarita
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SOFT tissue tumors , *SARCOMA , *GENE expression , *GENETIC overexpression , *INFANT diseases , *FOLLICULAR dendritic cells - Abstract
CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of "CIC-rearranged" sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
4. Process-based evaluation of carbon emissions from the on-site construction of prefabricated steel structures: A case study of a multistory data center in China.
- Author
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Huang, Zujian, Zhou, Hao, Tang, Hao, Zhang, Deyin, Zhao, Yang, Yu, Juan, Luo, Minjie, Wang, Yicheng, and Lin, Borong
- Abstract
Prefabricated steel structures are being promoted in China as an important measure to reduce building carbon emissions (CEs). Currently, high-quality carbon emission factors and calculation methods that identify the sources of CEs from construction process are lacking. This study proposed a process-based method for calculating on-site construction CEs and empirically demonstrated its feasibility using a case of a multistory steel structure with typical column-beam systems. Six construction processes comprising 38 subprocesses were first categorized, then the energy and materials consumed for each subprocess were determined to obtain the first-hand CE parameters. The CEs from hoisting the first- and second-section columns were 10.52 kgCO 2 /column and 14.41 kgCO 2 /column, respectively, and the CEs from their installation were in the range 38.16–69.18 kgCO 2 /column. The CEs from hoisting the primary and secondary beams using a car crane were 7.73 kgCO 2 /beam and 4.52 kgCO 2 /beam, respectively, with lower CEs of 2.40 kgCO 2 /beam and 2.22 kgCO 2 /beam, respectively when a tower crane was used for hoisting. The 14 connection types used to install the primary beams and the 11 connection types used to install the secondary beams had CEs of 13.84–125.96 kgCO 2 /beam and 10.39–43.49 kgCO 2 /beam, respectively. The total on-site construction CE was subsequently calculated by summing the CEs from each process. This method was able to track the CE sources for each construction process and their contributions to identify those with high CE intensities. In addition, the case study was evaluated to provide specific feedback on the current national standard for calculating CEs from building construction. • Proposed method for calculating steel construction carbon emissions. • Conducted on-site case study to determine process-specific carbon emissions. • Considered fuel, electricity, and material consumptions. • Evaluated the results to critique the current national calculation standard. • Gave suggestions to improve calculation for on-site construction carbon emissions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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5. Congenital tumors of the central nervous system: an institutional review of 64 cases with emphasis on tumors with unique histologic and molecular characteristics.
- Author
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Viaene, Angela N., Pu, Cunfeng, Perry, Arie, Li, Marilyn M., Luo, Minjie, and Santi, Mariarita
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TERATOCARCINOMA , *AUTOPSY , *TERATOMA , *CHOROID plexus , *BRAIN tumors ,CENTRAL nervous system tumors - Abstract
Congenital brain tumors are rare accounting for 0.5%–1.9% of all pediatric brain tumors. While different criteria have been used to classify a tumor as congenital, those diagnosed prior to 6 months of age are considered to be "probably" congenital in origin. We performed an institutional review of all central nervous system (CNS) tumors (surgical and autopsy specimens from 1990 to 2019) in patients less than 6 months old. Sixty‐four unique cases were identified, and these accounted for 2.0% of all CNS tumor specimens at our institution. The most common tumor types were high‐grade gliomas, low‐grade gliomas and medulloblastomas. Atypical teratoid rhabdoid tumors, choroid plexus tumors and germ cell tumors also accounted for a significant portion of the cohort. Seven tumors were diagnosed prenatally. The most common clinical presentation at diagnosis was increased head circumference. At the conclusion of the study, over half of the patients were alive including all patients with WHO grade I and II tumors. Ninety‐two percent of cases were classifiable using the 2016 WHO system, and when available, molecular findings supported the histologic diagnoses. However, several gliomas had unusual histologic features and did not correspond to a well‐defined entity. Molecular testing was essential for accurate classification of a subset of these tumors, and several high‐grade gliomas exhibited fusions considered unique to infantile gliomas, including those involving the MET, ALK and NTRK genes. To our knowledge, this cohort represents the largest single‐institution study of congenital CNS tumors and highlights many ways in which congenital CNS tumors are distinct from CNS tumors of older pediatric patients and adults. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
6. Patient specific circulating tumor DNA fingerprints to monitor treatment response across multiple tumors.
- Author
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Li, Jiaping, Jiang, Wei, Wei, Jinwang, Zhang, Jianwei, Cai, Linbo, Luo, Minjie, Wang, Zhan, Sun, Wending, Wang, Shengzhou, Wang, Chen, Dai, Chun, Liu, Jun, Wang, Guan, Wang, Jiping, Xu, Qiang, and Deng, Yanhong
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CIRCULATING tumor DNA , *DNA fingerprinting , *MULTIPLE tumors , *WILCOXON signed-rank test , *KRUSKAL-Wallis Test , *SOMATIC mutation - Abstract
Background: Circulating tumor DNA (ctDNA) offers a convenient way to monitor tumor progression and treatment response. Because tumor mutational profiles are highly variable from person to person, a fixed content panel may be insufficient to track treatment response in all patients.Methods: We design ctDNA fingerprint panels specific to individual patients which are based on whole exome sequencing and target to high frequency clonal population clusters in patients. We test the fingerprint panels in 313 patients who together have eight tumor types (colorectal, hepatocellular, gastric, breast, pancreatic, and esophageal carcinomas and lung cancer and cholangiocarcinoma) and exposed to multiple treatment methods (surgery, chemotherapy, radiotherapy, targeted-drug therapy, immunotherapy, and combinations of them). We also monitor drug-related mutations in the patients using a pre-designed panel with eight hotspot genes.Results: 291 (93.0%) designed fingerprint panels harbor less than ten previously known tumor genes. We detected 7475 ctDNA mutations in 238 (76%) patients and 6196 (96.0%) of the mutations are detected in only one test. Both the level of ctDNA content fraction (CCF) and fold change of CCF (between the definitive and proceeding tests) are highly correlated with clinical outcomes (p-values 1.36e-6 for level and 5.64e-10 for fold change, Kruskal-Wallis test). The CCFs of PD patients are an order of magnitude higher than the CCFs of SD and OR patients (median/mean 2.22%/8.96% for SD, 0.18/0.21% for PD, and 0.31/0.54% for OR; pairwise p-values 7.8e-6 for SD ~ PD, 2.7e-4 for OR ~ PD, and 7.0e-3 for SD ~ OR, Wilcoxon rank sum test). The fold change of CCF distinguishes the patient groups even better, which increases for PD, remains stable for SD, and decreases for OR patients (p-values 0.002, ~ 1, and 0.0001 respectively, Wilcoxon signed-rank test). Eleven drug-related mutations are identified from nine out of the 313 patients.Conclusions: The ctDNA fingerprint method improves both specificity and sensitivity of monitoring treatment response across several tumor types. It can identify tumor relapse/recurrence potentially earlier than imaging-based diagnosis. When augmented with tumor hotspot genes, it can track acquired drug-related mutations in patients. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
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7. Teriparatide induces angiogenesis in ischemic cerebral infarction zones of rats through AC/PKA signaling and reduces ischemia-reperfusion injury.
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Xiong, Moliang, Feng, Yun, Huang, Shujie, Lv, Siyuan, Deng, Yuhao, Li, Min, Wang, Pengfei, Luo, Minjie, Wen, Huangtao, and Zhang, Wangming
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CEREBRAL infarction , *TERIPARATIDE , *REPERFUSION injury , *CEREBRAL edema , *NEOVASCULARIZATION - Abstract
Teriparatide is a commonly used drug indicated for the treatment of osteoporosis in postmenopausal women. Teriparatide can also upregulate Ang-1 expression through the AC/PKA signaling pathway to promote angiogenesis. At present, promoting angiogenesis is a promising but unrealized strategy for the treatment of ischemic cerebral infarction. However, there are few studies on the application of teriparatide in the treatment of cerebral infarction. We used teriparatide to treat ischemic cerebral infarction in rats and obtained three major findings. First, teriparatide can promote angiogenesis, reduce cerebral infarct size, and increase cerebral perfusion by upregulating Ang-1 expression. Second, teriparatide can promote the expression of HO1, SOD2 and inhibit the production of pro-inflammatory cytokines IL-1β, IL-6 by upregulating Nrf2 expression. Third, we further found that teriparatide can mitigate blood-brain barrier disruption and brain edema by downregulating the expressions of MMP9, Ang-2 and AQP4. Our results indicate that teriparatide is neuroprotective through multiple mechanisms of action that include promoting angiogenesis, inhibiting oxidative stress and neuroinflammation, protecting blood-brain barrier, and reducing brain edema. [Display omitted] • Teriparatide promotes angiogenesis by upregulating Ang-1 expression. • Teriparatide plays a crucial role in inhibiting oxidative stress and anti-neuroinflammation. • Teriparatide can mitigate blood-brain barrier disruption and brain edema. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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