A5052688634- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Cell Adhesion Molecules Research
- Radiopharmaceutical Chemistry and Applications
- Cancer Genomics and Diagnostics
- Renal Diseases and Glomerulopathies
- Cancer Immunotherapy and Biomarkers
- Digestive system and related health
- Pancreatic and Hepatic Oncology Research
- Birth, Development, and Health
- RNA and protein synthesis mechanisms
- Nephrotoxicity and Medicinal Plants
- Genetic Syndromes and Imprinting
- Genetic and Kidney Cyst Diseases
- Genomics and Rare Diseases
- Vasculitis and related conditions
- Blood groups and transfusion
- Single-cell and spatial transcriptomics
- RNA Research and Splicing
- Acute Kidney Injury Research
- Erythrocyte Function and Pathophysiology
- Reproductive System and Pregnancy
- interferon and immune responses
- Adolescent and Pediatric Healthcare
Johns Hopkins University
2018-2024
Sidney Kimmel Comprehensive Cancer Center
2020-2023
Johns Hopkins Medicine
2019-2023
University of Baltimore
2020-2023
The First People's Hospital of Guiyang
2019-2021
Boston Children's Hospital
2018
Chongqing Medical University
2009
Children's Hospital of Chongqing Medical University
2009
Abstract Tumor mutation burden is an imperfect proxy of tumor foreignness and has therefore failed to consistently demonstrate clinical utility in predicting responses the context immunotherapy. We evaluated mutations regions genome that are unlikely undergo loss a pan-cancer analysis across 31 types ( n = 9,242) eight immunotherapy-treated cohorts patients with non-small-cell lung cancer, melanoma, mesothelioma, head neck cancer 524). discovered single-copy those present multiple copies per...
Computational prediction of binding between neoantigen peptides and major histocompatibility complex (MHC) proteins can be used to predict patient response cancer immunotherapy. Current predictors focus on in silico estimation MHC affinity are limited by low predictive value for actual peptide presentation, inadequate support rare alleles, poor scalability high-throughput data sets. To address these limitations, we developed MHCnuggets, a deep neural network method that predicts peptide-MHC...
Abstract Mesothelioma is a rare and fatal cancer with limited therapeutic options until the recent approval of combination immune checkpoint blockade. Here we report results phase 2 PrE0505 trial ( NCT02899195 ) anti-PD-L1 antibody durvalumab plus platinum-pemetrexed chemotherapy for 55 patients previously untreated, unresectable pleural mesothelioma. The primary endpoint was overall survival compared to historical control cisplatin pemetrexed chemotherapy; secondary exploratory endpoints...
To explore the approaches and diagnostic yield of genetic testing for renal disease in children, we describe genotype phenotype national cohort children with from 13 different regions China recruited 2014 to 2018 by building up multicenter registration system (Chinese Children Genetic Kidney Disease Database, CCGKDD). diagnosis was confirmed 42.1% our 1001 pediatric patients clinical suspicion a disease. Of 106 distinct monogenetic disorders detected, 15 accounted 60.7% diagnoses. The 29.1%...
In this study, we incorporate analyses of genome-wide sequence and structural alterations with pre- on-therapy transcriptomic T cell repertoire features in immunotherapy-naive melanoma patients treated immune checkpoint blockade. Although tumor mutation burden is associated improved treatment response, the frequency expressed genes superior predicting outcome. Increased density baseline tumors dynamic changes regression or expansion during therapy distinguish responders from non-responders....
Abstract Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer; however, little is known about genetic heterogeneity in these lesions. The objective of this study was characterize IPMNs at the single‐cell level. We isolated single cells from fresh tissue ten IPMNs, followed by whole genome amplification and targeted next‐generation sequencing driver genes. then determined genotypes using a novel multi‐sample mutation calling algorithm. Our analyses revealed...
<p>The supplementary figures file</p>
Background Nephronophthisis-related ciliopathies (NPHP-RC) account for the majority of cases monogenetically caused end-stage renal disease (ESRD) in children. Exploring correlation between phenotype and genotype NPHP-RC is helpful early diagnosis management. We investigated spectra a Chinese multicentre cohort. Methods Crosss-ectional longitudinal data 60 patients from 57 families with pathogenic gene mutations distributed 22 regions China were collected into unified, anonymous database....
Abstract The KPC mouse model, driven by the Kras and Trp53 transgenes, is well regarded for faithful recapitulation of human pancreatic cancer biology. However, extent that this model recapitulates subclonal evolution tumor type unknown. Here we report evidence continuing after initiation largely reflect copy number alterations target cellular processes established significance in cancer. evolutionary trajectories tumors show both linear branching patterns as clonal mixing. We propose...
Steroid-resistant nephrotic syndrome (SRNS) is one of the major causes end-stage kidney disease (ESKD) in children and young adults. For approximately 30% with SRNS results from a genetic cause. In this study, genotype-phenotype correlations cohort 283 pediatric patients or early-onset NS (nephrotic presenting within first year life) 23 nephrology centers China were analyzed. All performed next-generation sequencing Sanger sequencing. The overall mutation detection rate was 37.5% (106...
The magnitude of response to immune checkpoint inhibitor (ICI) therapy may be sex-dependent, as females have lower rates and decreased survival after ICI monotherapy. mechanisms underlying this sex dimorphism in are unknown, related sex-driven differences the immunogenomic landscape tumors that shape anti-tumor responses context therapy.
We present here a strategy to identify immunogenic neoantigen candidates from unique amino acid sequences at the junctions of fusion proteins which can serve as targets in development tumor vaccines for treatment breastcancer.We mined sequence reads breast tissue that are usually discarded discordant paired-end and discovered cancer specific transcripts using free controls reference. Binding affinity predictions novel peptide crossing junction were analyzed by MHC Class I binding predictor,...
Kidney disease is manifested in a wide variety of phenotypes, many which have an important hereditary component. To delineate the genotypic and phenotypic spectrum pediatric nephropathy, multicenter registration system being implemented based on Chinese Children Genetic Disease Database (CCGKDD). In this study, all patients with kidney urological diseases were recruited from 2014 to 2020. analysis was conducted using exome sequencing for families multiple affected individuals nephropathy or...
Abstract Background: Aberrant alternative splicing can generate neoantigens, which themselves stimulate immune responses and surveillance. Previous methods for quantifying splicing-derived neoantigens are limited by independent references potential batch effects. Results: Here, we introduce SpliceMutr, a bioinformatics approach pipeline identifying derived from tumor normal data. SpliceMutr facilitates the identification of tumor-specific antigenic splice variants, predicts MHC-binding...
<p>The supplementary figures file</p>
<p>Comparison of predicted splicing antigens from SpliceMutr to proteomics datasets. <b>A,</b> The log<sub>10</sub>-transformed total number MHC-binding kmers found with and without reference kmer filtering in all samples the breast cancer TCGA cohort (BRCA). <b>B,</b> percentage IEAtlas-validated immunogenic between (BRCA).</p>
<p>Per splice junction normalized SA for responders compared with baseline samples. The averaged across samples the subset of junctions derived from top 20 genes highest per sample. black horizontal line is median *, <i>P</i> value ≤ 0.05; **, 0.005; ***, 0.0005; ****, 0.00005. SA, splicing antigenicity.</p>
<div>Abstract<p>Aberrant alternative splicing can generate neoantigens, which themselves stimulate immune responses and surveillance. Previous methods for quantifying splicing-derived neoantigens are limited by independent references potential batch effects. Here, we introduce SpliceMutr, a bioinformatics approach pipeline identifying from tumor normal data. SpliceMutr facilitates the identification of tumor-specific antigenic splice variants, predicts MHC-binding affinity,...
<p>Pan-cancer correlation analysis of per-sample SA with nonsilent mutations in splicing machinery coding genes. Distribution per sample, averaged across genes, by the factor gene SF3B1 BRCA (<b>A</b>) or HNSC (<b>B</b>). *, <i>P</i> value ≤ 0.05. See TCGA cancer-type abbreviations Supplementary Table S1. SA, antigenicity.</p>