Biology subjects

Rennert, H.

Publications and source records attributed to Rennert, H..

3 recordsLinked to original sources

bioRxiv2021

Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 115 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS), remains poorly understood. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections. These results define both body-wide and tissue-specific (heart, liver, lung, kidney, and lymph nodes) damage wrought by the SARS-CoV-2 infection, evident as a function of varying viral load (high vs. low) during the course of infection and specific, transcriptional dysregulation in splicing isoforms, T cell receptor expression, and cellular expression states. In particular, cardiac and lung tissues revealed the largest degree of splicing isoform switching and cell expression state loss. Overall, these findings reveal a systemic disruption of cellular and transcriptional pathways from COVID-19 across all tissues, which can inform subsequent studies to combat the mortality of COVID-19, as well to better understand the molecular dynamics of lethal SARS-CoV-2 infection and other viruses.

microbiology↗

bioRxiv2020

Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling. We applied both technologies across 857 SARS-CoV-2 clinical specimens and 86 NYC subway samples, providing a broad molecular portrait of the COVID-19 NYC outbreak. Our results define new features of SARS-CoV-2 evolution, nominate a novel, NYC-enriched viral subclade, reveal specific host responses in interferon, ACE, hematological, and olfaction pathways, and examine risks associated with use of ACE inhibitors and angiotensin receptor blockers. Together, these findings have immediate applications to SARS-CoV-2 diagnostics, public health, and new therapeutic targets.

molecular biology↗

bioRxiv2017

Discovery and reporting of clinically-relevant germline variants in advanced cancer patients assessed using whole-exome sequencing

PurposeIn precision cancer care, WES-based analysis of tumor-normal samples helps reveal somatic alterations but can also identify cancer-associated germline variants important for disease surveillance, treatment choice and cancer prevention. WES can also identify germline secondary findings impacting risk of cardiac, neurodegenerative or metabolic diseases. In patients with advanced cancer, the frequency of reportable secondary findings encountered with WES is not well defined.\n\nMethodsTo address this question, we analyzed a cohort of 343 patients with advanced, metastatic cancer for whom we have performed tumor and germline WES interrogating more than 21,000 genes using a CLIA/CLEP approved assay.\n\nResults17% of patients in our cohort have one or more reportable germline variants, including patients with pathogenic variants in the BRCA1 and BRCA2 genes. The frequency of non-cancer clinically relevant germline variants (8.8%) was within the range of two control non-cancer cohorts (11.0% and 6.5%). The frequency of variants in cancer-associated genes was significantly higher (p<0.0005) in our advanced cancer cohort (8.2%) compared to control cohorts (2.7% and 3.8%). More than 50% of patients with reportable germline cancer variants had a family history of cancer.\n\nConclusionthese results stress the importance of returning germline results found during somatic genomic tumor testing.

genomics↗