A5022934719- Digestive system and related health
- Tissue Engineering and Regenerative Medicine
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Wnt/β-catenin signaling in development and cancer
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Endoplasmic Reticulum Stress and Disease
- Algorithms and Data Compression
- RNA modifications and cancer
- Biomedical Text Mining and Ontologies
- Immune Cell Function and Interaction
- AI-based Problem Solving and Planning
- Genomics and Chromatin Dynamics
- Nutrition, Genetics, and Disease
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Glycosylation and Glycoproteins Research
- Genetic factors in colorectal cancer
- Ubiquitin and proteasome pathways
- Machine Learning in Bioinformatics
- Protein Structure and Dynamics
Genentech
2001-2011
Angiogenesis Foundation
2011
National Center for Genome Resources
2010
University of Ottawa
2005
Bioinformatics Institute
2004
Stanford University
1995-2003
Stanford Medicine
1996
University Hospital and Clinics
1996
Next-generation sequencing captures sequence differences in reads relative to a reference genome or transcriptome, including splicing events and complex variants involving multiple mismatches long indels. We present computational methods for fast detection of short reads, based on successively constrained search process merging filtering position lists from genomic index. Our are implemented GSNAP (Genomic Short-read Nucleotide Alignment Program), which can align both single- paired-end as...
Exomes, transcriptomes and copy-number alterations in a sample of more than 70 primary human colonic tumours were analysed an attempt to characterize the genomic landscape; addition finding genes associated with commonly mutated signalling pathways, recurrent gene fusions involving R-spondin family members also found occur approximately 10% tumours, revealing potential new therapeutic target. An analysis exomes, colon matched normal controls has identified 35,000 protein-altering somatic...
We evaluated 25 protocol variants of 14 independent computational methods for exon identification, transcript reconstruction and expression-level quantification from RNA-seq data. Our results show that most algorithms are able to identify discrete components with high success rates but assembly complete isoform structures poses a major challenge even when all constituent elements identified. Expression-level estimates also varied widely across methods, based on similar models. Consequently,...
Identical (or more correctly 'monozygotic') twins are widely used to study the contributions of genetics and environment human disease. A that focused on three pairs monozygotic twins, in which one twin had multiple sclerosis other did not, has brought latest techniques genome sequencing analysis this field, incidentally published first female sequences. Full sequences were determined for pair these two mRNA transcriptome epigenome CD4+ lymphocytes determined. The striking result is no...
The genome of an anonymous Korean male has been sequenced using a broad spread genomic techniques. This combinatorial approach allows for detailed characterization sequence and structural variation. first four individual genomes to have determined spanned three distinct ethnic groups: Yoruba African, northwest European (Craig Venter James Watson) Han Chinese. new work, together with another reported elsewhere, adds the Altaic grouping list. Human sequences so far individuals ancestry in...
Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC). HBV integration into the host genome has been reported, but its scale, impact and contribution to HCC development not clear. Here, we sequenced tumor nontumor genomes (>80× coverage) transcriptomes of four patients identified 255 sites. Increased sequencing 240× coverage revealed proportionally higher number Clonal expansion HBV-integrated hepatocytes was found specifically in samples. We observe...
The anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) targets the B cell lineage marker FcRH5 expressed in multiple myeloma (MM) tumor cells. We demonstrate that TDBs trigger receptor activation by inducing target clustering and exclusion of CD45 phosphatase from synapse. dimensions molecule play a key role efficiency synapse formation. TDB kills human plasma cells patient-derived at picomolar concentrations results complete depletion bone marrow cynomolgus monkeys. These data...
Dual blockade of the PD-1 and TIGIT coinhibitory receptors on T cells shows promising early results in cancer patients. Here, we studied mechanisms whereby and/or modulate anti-tumor CD8+ cells. Although are thought to regulate different costimulatory (CD28 CD226), effectiveness or inhibition preclinical tumor models was reduced absence CD226. CD226 expression associated with clinical benefit patients non-small cell lung carcinoma (NSCLC) treated anti-PD-L1 antibody atezolizumab. CD28 were...
Analysis of splice variants from short read RNA-seq data remains a challenging problem. Here we present novel method for the genome-guided prediction and quantification events data, which enables analysis unannotated complex events. Splice junctions exons are predicted reads mapped to reference genome assembled into genome-wide graph. identified recursively graph quantified locally based on extending across start or end each variant. We assess accuracy simulated real illustrate how different...
CD8+ tissue-resident memory T (TRM) cells, marked by CD103 (ITGAE) expression, are thought to actively suppress cancer progression, leading the hypothesis that their presence in tumors may predict response immunotherapy.Here, we test this combining high-dimensional single-cell modalities with bulk tumor transcriptomics from 1868 patients enrolled lung and bladder clinical trials of atezolizumab (anti-programmed cell death ligand 1 (PD-L1)).ITGAE was identified as most significantly...
ABSTRACT Although many human immunodeficiency virus type 1 (HIV-1)-infected persons are treated with multiple protease inhibitors in combination or succession, mutation patterns of isolates from these have not been characterized. We collected and analyzed 2,244 subtype B HIV-1 1,919 different inhibitor experiences: 1,004 untreated persons, 637 who received one inhibitor, 603 receiving two more inhibitors. The median number mutations per isolate increased 4 to 12 had four Mutations at 45 the...
Abstract Breast cancers can be divided into subtypes with important implications for prognosis and treatment. We set out to characterize the genetic alterations observed in different breast cancer identify specific candidate genes pathways associated subtype biology. mRNA expression levels of estrogen receptor, progesterone HER2 were shown predict marker status determined by immunohistochemistry effective at assigning samples subtypes. HER2+ have greatest frequency high-level amplification...
Lung cancer is a highly heterogeneous disease in terms of both underlying genetic lesions and response to therapeutic treatments. We performed deep whole-genome sequencing transcriptome on 19 lung cell lines three tumor/normal pairs. Overall, our data show that line models exhibit similar mutation spectra human tumor samples. Smoker never-smoker samples distinguishable patterns mutations. A number epigenetic regulators, including KDM6A, ASH1L, SMARCA4, ATAD2, are frequently altered by...
We present a method for discovering conserved sequence motifs from families of aligned protein sequences. The has been implemented as computer program called emotif ( http://motif.stanford.edu/emotif ). Given an set sequences, generates with wide range specificities and sensitivities. also can generate that describe possible subfamilies superfamily. A disjunction such often represent the entire superfamily high specificity sensitivity. have used to sets all 7,000 alignments in blocks prints...
Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs), have been estimated using expressed sequence tag (EST) libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq) now makes it possible study occurrence and expression levels TICs individual samples genome.We performed single-end RNA-Seq on three human prostate adenocarcinoma their corresponding normal tissues, as well brain universal reference samples. We developed two...
Analysis of recurrent DNA amplification can lead to the identification cancer driver genes, but this process is often hampered by low resolution existing copy number analysis platforms. Fifty-one breast tumors were profiled for alterations (CNAs) with high-resolution Affymetrix 500K SNP array. These also expression-profiled and surveyed mutations in selected genes commonly mutated (TP53, CDKN2A, ERBB2, KRAS, PIK3CA, PTEN). Combined common CNAs revealed putative associations between features....