- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- CRISPR and Genetic Engineering
- Radiomics and Machine Learning in Medical Imaging
- Pituitary Gland Disorders and Treatments
- Cancer, Hypoxia, and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Viral gastroenteritis research and epidemiology
- Hepatitis B Virus Studies
- COVID-19 and healthcare impacts
- Cancer Immunotherapy and Biomarkers
- Cancer, Lipids, and Metabolism
- Brain Metastases and Treatment
- RNA and protein synthesis mechanisms
- Innovations in Medical Education
- Elbow and Forearm Trauma Treatment
- Immunotherapy and Immune Responses
- Genetic Mapping and Diversity in Plants and Animals
- Cancer-related molecular mechanisms research
- Evolution and Genetic Dynamics
- Orthopedic Surgery and Rehabilitation
- Cell Image Analysis Techniques
Massachusetts General Hospital
2017-2024
Harvard University
2011-2024
Massachusetts Institute of Technology
2023-2024
Broad Institute
2012-2024
Mass General Brigham
2024
Dana-Farber Brigham Cancer Center
2019-2021
Brigham and Women's Hospital
2019-2021
Dana-Farber Cancer Institute
2020-2021
Allen Institute
2021
Koch Institute for Integrative Cancer Research At MIT
2021
Identifying gene expression programs underlying both cell-type identity and cellular activities (e.g. life-cycle processes, responses to environmental cues) is crucial for understanding the organization of cells tissues. Although single-cell RNA-Seq (scRNA-Seq) can quantify transcripts in individual cells, each cell’s profile may be a mixture types programs, making them difficult disentangle. Here, we benchmark enhance use matrix factorization solve this problem. We show with simulations...
Although several hundred regions of the human genome harbor signals positive natural selection, few relevant adaptive traits and variants have been elucidated. Using full-genome sequence variation from 1000 Genomes (1000G) Project composite multiple (CMS) test, we investigated 412 candidate leveraged functional annotation, protein structure modeling, epigenetics, association studies to identify extensively annotate causal variants. The resulting catalog provides a tractable list for...
Background Lassa fever (LF), an often-fatal hemorrhagic disease caused by virus (LASV), is a major public health threat in West Africa. When the violent civil conflict Sierra Leone (1991 to 2002) ended, international consortium assisted restoration of LF program at Kenema Government Hospital (KGH) area with world's highest incidence disease. Methodology/Principal Findings Clinical and laboratory records patients presenting KGH Ward post-conflict period were organized electronically....
Liquid biopsies enable early detection and monitoring of diseases such as cancer, but their sensitivity remains limited by the scarcity analytes cell-free DNA (cfDNA) in blood. Improvements to have primarily relied on enhancing sequencing technology ex vivo. We sought transiently augment level circulating tumor (ctDNA) a blood draw attenuating its clearance report two intravenous priming agents given 1 2 hours before recover more ctDNA. Our consist nanoparticles that act cells responsible...
Craniopharyngiomas, primary brain tumors of the pituitary-hypothalamic axis, can cause clinically significant sequelae. Treatment with use surgery, radiation, or both is often associated substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% papillary craniopharyngiomas carry
Abstract Detecting mutations from single DNA molecules is crucial in many fields but challenging. Next-generation sequencing (NGS) affords tremendous throughput cannot directly sequence double-stranded (‘single duplexes’) to discern the true on both strands. Here we present Concatenating Original Duplex for Error Correction (CODEC), which confers duplex resolution NGS. CODEC 1,000-fold higher accuracy than NGS, using up 100-fold fewer reads sequencing. revealed mutation frequencies of 2.72 ×...
Rapidly evolving viruses and other pathogens can have an immense impact on human evolution as natural selection acts to increase the prevalence of genetic variants providing resistance disease. With emergence large datasets variation, we search for signatures in genome driven by such disease-causing microorganisms. Based this approach, previously hypothesized that Lassa virus (LASV) may been a driver West African populations where haemorrhagic fever is endemic. In study, provide further...
Natural selection in a Bangladeshi population from the cholera-endemic Ganges River Delta has targeted genes associated with cholera resistance and an innate immunity pathway activated by Vibrio cholerae .
Abstract Purpose While circulating tumor DNA (ctDNA) is a promising biomarker for minimal residual disease (MRD) detection in head and neck squamous cell carcinoma (HNSCC), more sensitive assays are needed accurate MRD at clinically-relevant timepoints. Ultrasensitive immediately after surgery could guide adjuvant therapy decisions, but early ctDNA dynamics poorly understood. Experimental Design We applied MAESTRO, whole-genome, tumor-informed, mutation-enrichment sequencing assay, pooled...
Abstract Infection with Lassa virus (LASV) can cause fever, a haemorrhagic illness an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity LASV infection, we carried out genome-wide association studies (GWAS) as well seroprevalence surveys, leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed fever susceptibility fatal outcomes 533...
Background: Effective physician leadership is critical to the future success of healthcare organizations. The American Academy Orthopaedic Surgeons (AAOS) Leadership Fellows Program a one-year program designed train young orthopaedic surgeons become leaders in orthopaedics. purpose this study was evaluate impact AAOS on skills and achievements its participants. Methods: Graduates were compared with control group previous applicants who not accepted (applicants) retrospective cohort...
Blood-based, or "liquid," biopsies enable minimally invasive diagnostics but have limits on sensitivity due to scarce cell-free DNA (cfDNA). Improvements primarily relied enhancing sequencing technology ex vivo . Here, we sought augment the level of circulating tumor (ctDNA) detected in a blood draw by attenuating clearance cfDNA We report first-in-class intravenous DNA-binding priming agent given 2 hours prior recover more cfDNA. The antibody minimizes nuclease digestion and organ uptake...
Abstract Background During the ongoing COVID-19 pandemic, contact with health care system for cancer treatment can increase risk of infection and associated mortality. Treatment recommendations must consider this elderly vulnerable patients. We reanalyzed trials in glioblastoma (GBM) patients, incorporating risk, order to provide a quantitative framework comparing different radiation (RT) fractionation schedules on patient outcomes. Methods extracted individual patient-level data 1321...
Abstract Identifying gene expression programs underlying both cell-type identity and cellular activities (e.g. life-cycle processes, responses to environmental cues) is crucial for understanding the organization of cells tissues. Although single-cell RNA-Seq (scRNA-Seq) can quantify transcripts in individual cells, each cell’s profile may be a mixture types programs, making them difficult disentangle. Here we illustrate enhance use matrix factorization as solution this problem. We show with...
<h3>Importance</h3> During the COVID-19 pandemic, cancer therapy may put patients at risk of SARS-CoV-2 infection and mortality. The impacts proposed alternatives on reducing are unknown. <h3>Objective</h3> To investigate how pandemic is associated with risks benefits standard radiation (RT). <h3>Design, Setting, Participants</h3> This comparative effectiveness study used estimated individual patient–level data extracted from published Kaplan-Meier survival figures 8 randomized clinical...