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PXD025265

PXD025265 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDrivers genes in severe forms of COVID-19
DescriptionThe etiology of severe forms of COVID19, especially in young patients, remains a salient unanswered question. Here we build on a 3-tier cohort where all individuals/patients were strictly below 50 years of age and where a number of comorbidities were excluded at study onset. Besides healthy controls (N=22), these include patients in the intensive care unit with Acute Respiratory Distress Syndrome (ARDS) (“critical group”; N=47), and those in a non-critical care ward under supplemental oxygen (“non-critical group”, N=25). This highly curated cohort allowed us to perform a deep multi-omics approach which included whole genome sequencing, whole blood RNA-sequencing, plasma and peripheral-blood mononuclear cells proteomics, multiplex cytokine profiling, mass-cytometry-based immune cell profiling in conjunction with viral parameters i.e. anti-SARS-Cov-2 neutralizing antibodies and multi-target antiviral serology. Critical patients were characterized by an exacerbated inflammatory state, perturbed lymphoid and myeloid cell compartments, signatures of dysregulated blood coagulation and active regulation of viral entry into the cells. A unique gene signature that differentiates critical from non-critical patients was identified by an ensemble machine learning, deep learning and quantum computing approach. Within this gene network, Structural Causal Modeling identified several ARDS driver genes, among which the up-regulated metalloprotease ADAM9 seems to be a key driver. Inhibition of ADAM9 ex vivo interfered with SARS-Cov-2 uptake and replication in human epithelial cells. Hence we apply a machine learning approach to identify driver genes for severe forms of COVID-19 in a small, uncluttered cohort of patients.
HostingRepositoryPRIDE
AnnounceDate2021-11-25
AnnouncementXMLSubmission_2021-11-25_07:27:26.141.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAurélie Hirschler
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-04-08 06:01:28ID requested
12021-11-25 07:27:26announced
Publication List
Dataset with its publication pending
Keyword List
ProteomeXchange project tag: Sars-cov-2, Covid-19
submitter keyword: SARS-CoV-2, COVID-19, Acute Respiratory Distress Syndrome, mechanical ventilation, multi-omics, artificial intelligence, machine learning, disease severity signatures, therapeutic targets, ADAM9
Contact List
Christine Carapito
contact affiliationLaboratoire de Spectrométrie de Masse BioOrganique, Université de Strasbourg, CNRS, IPHC, UMR 7178, Strasbourg, France
contact emailccarapito@unistra.fr
lab head
Aurélie Hirschler
contact affiliationLSMBO, IPHC
contact emailaurelie.hirschler@unistra.fr
dataset submitter
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