A5047116900- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- CAR-T cell therapy research
- Biochemical and Molecular Research
- Pediatric health and respiratory diseases
- Cytomegalovirus and herpesvirus research
- T-cell and B-cell Immunology
- Molecular Biology Techniques and Applications
- Microbial Fuel Cells and Bioremediation
- Hearing, Cochlea, Tinnitus, Genetics
- Clostridium difficile and Clostridium perfringens research
- Lung Cancer Research Studies
- Cancer, Hypoxia, and Metabolism
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- bioluminescence and chemiluminescence research
- Wnt/β-catenin signaling in development and cancer
- Gut microbiota and health
- DNA Repair Mechanisms
- Cancer-related gene regulation
- Single-cell and spatial transcriptomics
University of Pennsylvania
2017-2024
Columbia University
2014-2016
University of Cincinnati Medical Center
2016
Cornell University
2014
The ubiquity of RNA-seq has led to many methods that use data analyze variations in RNA splicing. However, available are not well suited for handling heterogeneous and large datasets. Such datasets scale thousands samples across dozens experimental conditions, exhibit increased variability compared biological replicates, involve unannotated splice variants resulting transcriptome complexity. We describe here a suite algorithms tools implemented the MAJIQ v2 package address challenges...
Abstract Microbial colonization of the infant gastrointestinal tract (GIT) begins at birth, is shaped by maternal microbiota, and profoundly altered antibiotic treatment. Antibiotic treatment mothers during pregnancy influences GIT microbiota their infants. The role in regulating adaptive immune function against systemic viral infections infancy remains undefined. We used a mouse model perinatal exposure to examine effect microbial dysbiosis on CD8+ T cell–mediated antiviral immunity....
Cells adjust to hypoxic stress within the tumor microenvironment by downregulating energy-consuming processes including translation. To delineate mechanisms of cellular adaptation hypoxia, we performed RNA-Seq normoxic and head neck cancer cells. These data revealed a significant down regulation genes known regulate RNA processing splicing. Exon-level analyses classified > 1,000 mRNAs as alternatively spliced under hypoxia uncovered unique retained intron (RI) in master regulator translation...
Abstract Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) is a major cause of pediatric cancer–related deaths. Relapse-specific mutations do not account for all chemotherapy failures in B-ALL patients, suggesting additional mechanisms resistance. By mining RNA sequencing datasets paired diagnostic/relapse samples, we discovered pervasive alternative splicing (AS) patterns linked to relapse and affecting drivers resistance glucocorticoids, antifolates, thiopurines. Most...
Alternative pre-mRNA splicing has long been proposed to contribute greatly proteome complexity. However, the extent which mature mRNA isoforms are successfully translated into protein remains controversial. Here, we used high-throughput RNA sequencing and mass spectrometry (MS)–based proteomics better evaluate translation of alternatively spliced mRNAs. To increase coverage improve quantitation, optimized cell fractionation sample processing steps at both peptide level. Furthermore,...
Abstract The effects of confounding factors on gene expression analysis have been extensively studied following the introduction high-throughput microarrays and subsequently RNA sequencing. In contrast, there is a lack equivalent tools for splicing. Here we first assess effect confounders both splicing quantifications in two large public RNA-Seq datasets (TARGET, ENCODE). We show quantification variations are affected at least as much those expression, revealing unwanted sources datasets....
RNA-sequencing (RNA-seq) is widely adopted for transcriptome analysis but has inherent biases which hinder the comprehensive detection and quantification of alternative splicing. To address this, we present an efficient targeted RNA-seq method that greatly enriches splicing-informative junction-spanning reads. Local Splicing Variation sequencing (LSV-seq) utilizes multiplexed reverse transcription from highly scalable pools primers anchored near splicing events interest. Primers are designed...
Alternative splicing occurs in the vast majority of human genes, giving rise to distinct mRNA and protein isoforms. We, others, have previously identified hundreds genes that change their isoform expression upon T cell activation via alternative splicing; however, how these changes link input with functional output remains largely unknown. Here, we investigate costimulation cells through CD28 receptor impacts activated (TCR, CD3) find while signaling alone has minimal impact on splicing, it...
GB virus C (GBV-C) is a non-pathogenic flavivirus that may play role in modulating HIV disease. Multiple genotypes of GBV-C have been identified to date differentially regulate HIV; however, the number complete sequences published very limited. We sequenced full-length genomes from four individuals with HIV/HCV co-infection United States. Intergenotypic recombination was evident two these individuals. Evaluation additional would facilitate creation full-length, replication-competent...
The ubiquity of RNA-seq has led to many methods that use data analyze variations in RNA splicing. However, available are not well suited for handling heterogeneous and large datasets. Such datasets scale thousands samples across dozens experimental conditions, exhibit increased variability compared biological replicates, involve unannotated splice variants resulting transcriptome complexity. We describe here a suite algorithms tools implemented the MAJIQ v2 package address challenges...
<p>Supplementary Methods and Figures S1-S3</p>
<div>Abstract<p>Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) is a major cause of pediatric cancer–related deaths. Relapse-specific mutations do not account for all chemotherapy failures in B-ALL patients, suggesting additional mechanisms resistance. By mining RNA sequencing datasets paired diagnostic/relapse samples, we discovered pervasive alternative splicing (AS) patterns linked to relapse and affecting drivers resistance glucocorticoids, antifolates,...
Abstract RNA sequencing (RNA-seq) is widely adopted for transcriptome analysis but has inherent biases that hinder the comprehensive detection and quantification of alternative splicing. To address this, we present an efficient targeted RNA-seq method greatly enriches splicing-informative junction-spanning reads. Local splicing variation (LSV-seq) utilizes multiplexed reverse transcription from highly scalable pools primers anchored near events interest. Primers are designed using Optimal...
Summary Distinct T cell subtypes are typically defined by the expression of distinct gene repertoires. However, there is variability between studies regarding markers used to define each subtype. Moreover, previous analysis in subsets has largely focused on rather than alternative splicing. Here we take a meta-analysis approach, comparing eleven independent RNA-Seq human Th1, Th2, Th17 and/or Treg cells identify transcriptomic features that correlate consistently with We find known...
Abstract Alternative splicing occurs in the vast majority of human genes, giving rise to distinct mRNA and protein isoforms. We, others, have previously identified hundreds genes that change their isoform expression upon T cell activation via alternative splicing; however, how these changes link input with functional output remains largely unknown. Here we investigate costimulation cells through CD28 receptor impacts activated (CD3) find while signaling alone has minimal impact on splicing,...
Abstract Infancy and childhood is a critical period for the development of long-term immune function. Normal acquisition gastrointestinal (GIT) flora during this now appreciated in its role on system Antibiotics cause GIT dysbiosis may alter normal colonization infancy. Subsequently, function also be affected. In infant mouse model antibiotic mediated dysbiosis, perinatal treatment (AT) alters composition mothers their infants. CD8+ T cells from AT mice activated vitro with cytokines,...
Relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) is a major cause of pediatric cancer-related deaths. Relapse-specific mutations do not account for all chemotherapy failures in B- ALL patients, suggesting additional mechanisms resistance. By mining RNA-seq datasets paired diagnostic/relapse B-ALL samples, we discovered pervasive alternative splicing (AS) patterns linked to relapse and affecting drivers resistance glucocorticoids, anti-folates, thiopurines. Most variations...