A5034496465- Estrogen and related hormone effects
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- HER2/EGFR in Cancer Research
- Epigenetics and DNA Methylation
- Glioma Diagnosis and Treatment
- Computational Drug Discovery Methods
- Genomics and Chromatin Dynamics
- Colorectal Cancer Treatments and Studies
- Gene expression and cancer classification
- Genomics and Phylogenetic Studies
- Bioinformatics and Genomic Networks
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Speech Recognition and Synthesis
- vaccines and immunoinformatics approaches
- Speech and Audio Processing
- Monoclonal and Polyclonal Antibodies Research
- Ferroptosis and cancer prognosis
- Cytokine Signaling Pathways and Interactions
- Molecular Biology Techniques and Applications
- SARS-CoV-2 and COVID-19 Research
- Machine Learning in Bioinformatics
- Blind Source Separation Techniques
- CAR-T cell therapy research
National Cancer Institute
2018-2025
Center for Cancer Research
2020-2025
National Institutes of Health
2018-2025
Cancer Institute (WIA)
2019-2024
Dana-Farber Cancer Institute
2023
Government of the United States of America
2021
University of Maryland, College Park
2017-2019
University of California, Berkeley
2018
École Polytechnique Fédérale de Lausanne
2010-2016
SIB Swiss Institute of Bioinformatics
2014
Metabolic pathways fuel tumor progression and resistance to stress conditions including chemotherapeutic drugs, such as DNA damage response (DDR) inhibitors. Yet, significant gaps persist in how metabolic confer DDR inhibition cancer cells. Here, we employed a metabolism-focused CRISPR knockout screen identified genetic vulnerabilities We unveiled Peroxiredoxin 1 (PRDX1) synthetic lethality partner with Ataxia Telangiectasia Mutated (ATM) kinase. Tumor cells depleted of PRDX1 displayed...
Synthetic lethal combination induces ferroptosis.
Abstract Combination of anti-cancer drugs is broadly seen as way to overcome the often-limited efficacy single agents. The design and testing combinations are however very challenging. Here we present a uniquely large dataset screening over 5000 targeted agent across 81 non-small cell lung cancer lines. Our analysis reveals profound heterogeneity response tumor models. Notably, rarely result in strong gain range observable with Importantly, activity agents more often when co-targeting...
Abstract Drugs that kill tumors through multiple mechanisms have the potential for broad clinical benefits. Here, we first developed an in silico multiomics approach (BipotentR) to find cancer cell–specific regulators simultaneously modulate tumor immunity and another oncogenic pathway then used it identify 38 candidate immune–metabolic regulators. We show activities of these stratify patients with melanoma by their response anti–PD-1 using machine learning deep neural approaches, which...
Leaf senescence is the orderly dismantling of older tissue that allows recycling nutrients to developing portions plant and accompanied by major changes in gene expression. Histone modifications correlate levels expression, this study utilizes ChIP-seq classify activating H3K4me3 silencing H3K27me3 marks on a genome-wide scale for soil-grown mature naturally senescent Arabidopsis leaves. ChIPnorm was used normalize data sets identify genomic regions with significant differences two histone...
Precision oncology is gradually advancing into mainstream clinical practice, demonstrating significant survival benefits. However, eligibility and response rates remain limited in many cases, calling for better predictive biomarkers.We present ENLIGHT, a transcriptomics-based computational approach that identifies clinically relevant genetic interactions uses them to predict patient's variety of therapies multiple cancer types without training on previous treatment data. We study ENLIGHT two...
Malignant mesothelioma is an aggressive cancer with limited treatment options and poor prognosis. A better understanding of genomics transcriptomics could advance therapies. Here, we present a cohort 122 patients along their germline tumor whole-exome RNA sequencing data as well phenotypic drug response information. We identify 48-gene prognostic signature that highly predictive patient survival, including CCNB1, the expression which survival on its own. In addition, analyze to study immune...
The co-occurrence of chromosome 10 loss and 7 gain in gliomas is the most frequent loss-gain co-aneuploidy pair human cancers. This phenomenon has been investigated since late 1980s without resolution. Expanding beyond previous gene-centric studies, we a genome-wide manner, taking an evolutionary perspective. Mining large-scale tumor aneuploidy data confirmed finding small-scale longitudinal study that likely order loss, followed by gain. Extensive analysis genomic transcriptomic from both...
The efficacy of prospective cancer treatments is routinely estimated by in vitro cell-line proliferation screens. However, it unclear whether tumor aggressiveness and patient survival are influenced more the proliferative or migratory properties cells. To address this question, we experimentally measured migration phenotypes across than 40 breast cell-lines. Based on latter, built validated individual predictors levels from cells' transcriptomics. We then apply these to estimate 1000 TCGA...
Abstract Epithelial lineage differentiation is pivotal to mammary gland development and it can pause metastasis of breast cancer (BC) by inducing tumor dormancy. To simulate this, we expressed epithelial genes in mesenchymal BC cells. Inducible expression the OVOL metastatic cells suppressed proliferation migration. We found that C1ORF116 , an OVOL’s target, susceptible genetic epigenetic aberrations BC. It regulated steroids functions as a putative autophagy receptor inhibits antioxidants...
Precision oncology is increasingly becoming integral to clinical practice, showing notable improvements in treatment outcomes. While molecular data such as gene expression and methylation profiles offer comprehensive insights, obtaining this costly slow. Addressing challenge, here we developed Path2Omics, a deep learning model that predicts from histopathology. Path2Omics was trained on 20,497 slides (a combination of 9,456 formalin fixed (FFPE) 11,041 fresh frozen (FF)) 8,007 patients...
Cellular plasticity mediates tissue development as well cancer growth and progression. In breast cancer, a shift to more epithelial phenotype (epithelialization) underlies state of reversible cell arrest called tumor dormancy, which enables drug resistance, recurrence, metastasis. Here, we explored the mechanisms driving epithelialization dormancy in aggressive mesenchymal-like cells three-dimensional cultures. Overexpressing either lineage-associated transcription factors OVOL1 or OVOL2...
The advent of high-throughput technologies such as ChIP-seq has made possible the study histone modifications. A problem particular interest is identification regions genome where different cell types from same organism exhibit patterns enrichment. This turns out to be surprisingly difficult, even in simple pairwise comparisons, because significant level noise data. In this paper we propose a two-stage statistical method, called ChIPnorm, normalize data, and find differential genome, given...
The tumor suppressor Hippo pathway negatively regulates the transcriptional coactivators Yes-associated protein (YAP) and coactivator with PDZ-binding motif (TAZ) to inhibit cell growth control organ size, whereas activation of YAP TAZ is implicated in tumorigenesis cancer metastasis. Here, we report that nonreceptor tyrosine kinase PYK2 positively activity triple-negative breast (TNBC). We found inhibition expression or its substantially affects steady-state level markedly facilitates...
Article12 March 2019Open Access Transparent process Genome-wide prediction of synthetic rescue mediators resistance to targeted and immunotherapy Avinash Das Sahu Corresponding Author [email protected] orcid.org/0000-0002-2193-6276 Department Biostatistics Computational Biology, Harvard School Public Health, Boston, MA, USA Medicine Medical School, Massachusetts General Hospital Cancer Center, University Maryland Institute Advanced Computer Science (UMIACS), Maryland, College Park, MD,...
The co-occurrence of chromosome 10 loss and 7 gain in gliomas is the most frequent loss-gain co-aneuploidy pair human cancers, a phenomenon that has been investigated without resolution since late 1980s. Expanding beyond previous gene-centric studies, we investigate genome-wide manner taking an evolutionary perspective. First, by mining large tumor aneuploidy data, predict more likely order followed gain. Second, analyzing extensive genomic transcriptomic data from both patients cell lines,...
Expression pattern of synthetic lethality genes is a previously unknown factor associated with cancer risk across human tissues.
Metastasis is a leading cause of cancer-related deaths, yet understanding how metastatic tumors adapt from their origin to target tissues remains fundamental challenge. To address this, we assessed whether primary and more closely resemble or in terms gene expression. We analyzed expression profiles multiple cancer types normal tissues, including single-cell bulk RNA sequencing data both paired unpaired patient cohorts. Primary were overall transcriptomically similar origin, while metastases...
Cancer is a predominant disease across animals. We applied comparative genomics approach to systematically characterize genes whose conservation levels correlate positively (PC) or negatively (NC) with cancer resistance estimates 193 vertebrates. Pathway analysis reveals that NC are enriched for metabolic functions and PC in cell cycle regulation, DNA repair, immune response, pointing their corresponding roles mediating risk. find less tolerant loss-of-function (LoF) mutations, driver genes,...
In cell differentiation, a of less specialized type becomes one more type, even though all cells have the same genome. Transcription factors and epigenetic marks like histone modifications can play significant role in differentiation process. this paper, we present simple analysis types paths using phylogenetic inference based on ChIP-Seq modification data. We precisely defined notion cell-type trees provided procedure building such trees. propose new data representation techniques distance...
Motivation: We have witnessed an enormous increase in ChIP-Seq data for histone modifications the past few years. Discovering significant patterns these is important problem understanding biological mechanisms. Results: propose probabilistic partitioning methods to discover data. Our take into account signal magnitude, shape, strand orientation and shifts. compare our with some current demonstrate improvements, especially sparse Besides pattern discovery classification, can serve other...
Novel strategies are needed to identify drug targets and treatments for the COVID-19 pandemic. The altered gene expression of virus-infected host cells provides an opportunity specifically inhibit viral propagation via targeting synthetic lethal dosage (SL/SDL) partners such genes. Pursuing this disparate antiviral strategy, here we comprehensively analyzed multiple