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To elucidate the molecular mechanisms that manifest lung abnormalities during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, we performed whole-transcriptome sequencing of lung autopsies from 31 patients with severe COVID-19 and ten uninfected controls. Using metatranscriptomics, we identified the existence of two distinct molecular signatures of lethal COVID-19. The dominant 'classical' signature (n=23) showed upregulation of the unfolded protein response, steroid biosynthesis and complement activation, supported by massive metabolic reprogramming leading to characteristic lung damage. The rarer signature (n=8) that potentially represents 'cytokine release syndrome' (CRS) showed upregulation of cytokines such as IL1 and CCL19, but absence of complement activation. We found that a majority of patients cleared SARS-CoV-2 infection, but they suffered from acute dysbiosis with characteristic enrichment of opportunistic pathogens such as Staphylococcus cohnii in 'classical' patients and Pasteurella multocida in CRS patients. Our results suggest two distinct models of lung pathology in severe COVID-19 patients, which can be identified through complement activation, presence of specific cytokines and characteristic microbiome. These findings can be used to design personalized therapy using in silico identified drug molecules or in mitigating specific secondary infections.
Pubmed ID: 35438176 RIS Download
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A web-based gene list enrichment analysis tool that provides various types of visualization summaries of collective functions of gene lists. It includes new gene-set libraries, an alternative approach to rank enriched terms, and various interactive visualization approaches to display enrichment results using the JavaScript library, Data Driven Documents (D3). The software can also be embedded into any tool that performs gene list analysis. System-wide profiling of genes and proteins in mammalian cells produce lists of differentially expressed genes / proteins that need to be further analyzed for their collective functions in order to extract new knowledge. Once unbiased lists of genes or proteins are generated from such experiments, these lists are used as input for computing enrichment with existing lists created from prior knowledge organized into gene-set libraries.
View all literature mentionsOriginal SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.
View all literature mentionsA catalog of gene-expression data collected from human cells treated with chemical compounds and genetic reagents. Computational methods to reduce the number of necessary genomic measurements along with streamlined methodologies enable the current effort to significantly increase the size of the CMap database and along with it, our potential to connect human diseases with the genes that underlie them and the drugs that treat them. The NIH has funded a large expansion of the Connectivity Map dataset through the Library of Integrated Network-based Cellular Signatures (LINCS). The Broad Institute's LINCS center aims to create a first installment of data generation and analysis for the LINCS program. Through these data LINCS intends to accelerate the discovery process by systematically revealing connections between genes/compounds discovered in screens and molecular pathways that underlie disease states.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsHigh quality ribosomal RNA databases providing comprehensive, quality checked and regularly updated datasets of aligned small (16S/18S, SSU) and large subunit (23S/28S, LSU) ribosomal RNA (rRNA) sequences for all three domains of life (Bacteria, Archaea and Eukarya). Supplementary services include a rRNA gene aligner, online tools for probe and primer evaluation and optimized browsing, searching and downloading on the website. The extensively curated SILVA taxonomy and the new non-redundant SILVA datasets provide an ideal reference for high-throughput classification of data from next-generation sequencing approaches. Alignment tool, SINA, is available for download as well as available for use online.
View all literature mentionsSoftware Java pipeline for trimming tasks for Illumina paired end and single ended data. Flexible Trimmer for Illumina Sequence Data. Pair aware preprocessing tool optimized for Illumina next generation sequencing data. Includes several processing steps for read trimming and filtering. Operating systems Unix/Linux, Mac OS, Windows.
View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsData sharing repository of clinical trials, associated mechanistic studies, and other basic and applied immunology research programs. Platform to store, analyze, and exchange datasets for immune mediated diseases. Data supplied by NIAID/DAIT funded investigators and genomic, proteomic, and other data relevant to research of these programs extracted from public databases. Provides data analysis tools and immunology focused ontology to advance research in basic and clinical immunology.
View all literature mentionsA read summarization program, which counts mapped reads for the genomic features such as genes and exons.
View all literature mentionsSoftware for handling and analysis of high-throughput microbiome census data.
View all literature mentionsQuality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.
View all literature mentionsOpen source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.
View all literature mentionsHuman and mouse genome annotation project which aims to identify all gene features in the human genome using computational analysis, manual annotation, and experimental validation.
View all literature mentionsData aggregate that compiles results from bioinformatics analyses across multiple samples into a single report. It is written in Python.
View all literature mentionsOpen source project to harness scientific and public health potential of pathogen genome data. Provides continually updated view of publicly available data alongside powerful analytic and visualization tools for use by community. Used to aid epidemiological understanding and improve outbreak response. Open source SARS-CoV-2 genome data and analytic and visualization tools.
View all literature mentionsPortal to share hCoV-19 genome sequences. Collection of genome sequences and related clinical and epidemiological data associated with coronavirus hCoV-19. Global repository of SARS-CoV-2 genomes. Initiative involves public-private-partnerships between Freunde of GISAID and governments of Federal Republic of Germany, Singapore and United States of America, with support from private and corporate philanthropy.International database of hCoV-19 genome sequences and related clinical and epidemiological data. Resource for influenza and hCoV-19 data.
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