Shankara Anand
A5057261462- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- Peptidase Inhibition and Analysis
- Cancer Genomics and Diagnostics
- Multiple Myeloma Research and Treatments
- Lung Cancer Research Studies
- Genetic Associations and Epidemiology
- Single-cell and spatial transcriptomics
- Bioinformatics and Genomic Networks
- Acute Myeloid Leukemia Research
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Ferroptosis and cancer prognosis
- Molecular Biology Techniques and Applications
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Extracellular vesicles in disease
- Chemokine receptors and signaling
- CRISPR and Genetic Engineering
- Gene expression and cancer classification
- Genomics and Chromatin Dynamics
- Glycosylation and Glycoproteins Research
- SARS-CoV-2 and COVID-19 Research
- Renal cell carcinoma treatment
- Advanced Proteomics Techniques and Applications
Boston University
2021-2024
Broad Institute
2018-2024
Massachusetts Institute of Technology
2021-2024
Boston Medical Center
2024
Stanford Medicine
2024
Amyloidosis Foundation
2024
Harvard University
2021
Thermo Fisher Scientific (Sweden)
2020
Novartis (United States)
2019
Stanford University
2018
The Genotype-Tissue Expression (GTEx) project dissects how genetic variation affects gene expression and splicing.
Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex in gene expression and genetic regulation across 44 tissue sources surveyed by Genotype-Tissue Expression project (GTEx, v8 release). demonstrate that influences levels cellular composition samples body. A total 37% all genes sex-biased at least one tissue. identify cis quantitative trait loci (eQTLs)...
Cell type composition, estimated from bulk tissue, maps the cellular specificity of genetic variants.
Telomere length within an individual varies in a correlated manner across most tissues.
Understanding gene function and regulation in homeostasis disease requires knowledge of the cellular tissue contexts which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen types from 16 donors 25 samples, generating a cross-tissue atlas 209,126 nuclei profiles, integrated across tissues, donors, laboratory with conditional variational autoencoder. Using resulting atlas, highlight shared tissue-specific features...
Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape LSCC, providing deeper exposition LSCC biology potential implications. identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 overexpressing target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such LSD1 EZH2 to SOX2-overexpressing tumors. Our data support...
Abstract Current genomics methods are designed to handle tens thousands of samples but will need scale millions match the pace data and hypothesis generation in biomedical science. Here, we show that high efficiency at low cost can be achieved by leveraging general-purpose libraries for computing using graphics processing units (GPUs), such as PyTorch TensorFlow. We demonstrate > 200-fold decreases runtime ~ 5–10-fold reductions relative CPUs. anticipate accessibility these lead a...
PURPOSE Smoldering multiple myeloma (SMM) is a precursor condition of (MM) with 10% annual risk progression. Various prognostic models exist for stratification; however, those are based on solely clinical metrics. The discovery genomic alterations that underlie disease progression to MM could improve current models. METHODS We used next-generation sequencing study 214 patients SMM. performed whole-exome 166 tumors, including 5 serial samples, and deep targeted 48 tumors. RESULTS observed...
Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology both normal cancer cells. Advances mass spectrometry enable high-throughput, accurate, sensitive measurement of PTM levels to better understand their role, prevalence, crosstalk. Here, we analyze the largest collection proteogenomics data from 1,110 patients with profiles across 11 types (10 National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals...
Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying significant cis-effects and distal trans-effects quantified at RNA, protein, phosphoprotein levels. Salient observations include association point mutations copy-number alterations with rewiring protein interaction networks,...
Despite the successes of immunotherapy in cancer treatment over recent decades, less than <10%–20% cases have demonstrated durable responses from immune checkpoint blockade. To enhance efficacy immunotherapies, combination therapies suppressing multiple evasion mechanisms are increasingly contemplated. better understand cell surveillance and diverse tumor tissues, we comprehensively characterized landscape more 1,000 tumors across ten different cancers using CPTAC pan-cancer proteogenomic...
Outliers in the human transcriptome reveal functional effects of rare genetic variants.
Abstract Allele expression (AE) analysis robustly measures cis -regulatory effects. Here, we present and demonstrate the utility of a vast AE resource generated from GTEx v8 release, containing 15,253 samples spanning 54 human tissues for total 431 million measurements at SNP level 153 haplotype level. In addition, develop an extension our tool phASER that allows effect sizes variants to be estimated using haplotype-level data. This is largest date, are able make data publicly available. We...
Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or experience breakthrough infections. Understanding common host factors necessary for life cycles of may reveal conserved therapeutic targets. Here, we used known substrate specificities mammalian protein kinases to deconvolute...
Abstract Multiple myeloma is a plasma cell malignancy almost always preceded by precursor conditions, but low tumor burden of these early stages has hindered the study their molecular programs through bulk sequencing technologies. Here, we generate and analyze single RNA-sequencing cells from 26 patients at varying disease 9 healthy donors. In silico dissection comparison normal transformed same bone marrow biopsy enables discovery patient-specific transcriptional changes. Using Non-Negative...
DNA methylation plays a critical role in establishing and maintaining cellular identity. However, it is frequently dysregulated during tumor development closely intertwined with other genetic alterations. Here, we leveraged multi-omic profiling of 687 tumors matched non-involved adjacent tissues from the kidney, brain, pancreas, lung, head neck, endometrium to identify aberrant associated RNA protein abundance changes build Pan-Cancer catalog. We uncovered lineage-specific epigenetic drivers...
Non-clear cell renal carcinomas (non-ccRCCs) encompass diverse malignant and benign tumors. Refinement of differential diagnosis biomarkers, markers for early prognosis aggressive disease, therapeutic targets to complement immunotherapy are current clinical needs. Multi-omics analyses 48 non-ccRCCs compared with 103 ccRCCs reveal proteogenomic, phosphorylation, glycosylation, metabolic aberrations in RCC subtypes. RCCs high genome instability display overexpression IGF2BP3 PYCR1. Integration...
ABSTRACT While vaccines are vital for preventing COVID-19 infections, it is critical to develop new therapies treat patients who become infected. Pharmacological targeting of a host factor required viral replication can suppress spread with low probability mutation leading resistance. In particular, kinases highly druggable targets and number conserved coronavirus proteins, notably the nucleoprotein (N), require phosphorylation full functionality. order understand how could be used...
Clonal hematopoiesis results from somatic mutations in cancer driver genes hematopoietic stem cells. We sought to identify novel drivers of clonal expansion using an unbiased analysis sequencing data 84,683 persons and identified common the 5-methylcytosine reader,
The acid–base dissociation constant, pKa, is a key parameter to define the ionization state of compound and directly affects its biopharmaceutical profile. In this study, we developed novel approach for pKa prediction using rooted topological torsion fingerprints in combination with five machine learning (ML) methods: random forest, partial least squares, extreme gradient boosting, lasso regression, support vector regression. With large diverse set 14 499 experimental values, models were...