PXD022091

PXD022091 is an original dataset announced via ProteomeXchange.

Title	Integration of Protein Interactome Data with Congenital Heart Disease Variants Reveals Disease Genes
Description	Congenital Heart Disease (CHD) accounts for 1% of birth defects, and while large-scale genetic studies have uncovered genes associated with CHDs, identifying causal mutations remains a challenge. We hypothesized that genetic determinants for CHDs could be found in the protein interactomes of GATA4 and TBX5, two cardiac transcription factors (TFs) associated with CHDs. Defining their interactomes in human cardiac progenitors via affinity purification-mass spectrometry and integrating the results with genetic data from the Pediatric Cardiac Genomic Consortium (PCGC) revealed an enrichment of de novo variants among proteins that interact with GATA4 or TBX5. A consolidative score designed to prioritize TF interactome members based on distinctive variant, gene and proband features identified numerous likely CHD-causing genes, including the epigenetic reader GLYR1. GLYR1 and GATA4 widely co-occupied cardiac developmental genes resulting in co-activation and the GLYR1 variant associated with CHD disrupted interaction with GATA4. This integrative proteomic and genetic approach provides a framework for prioritizing and interrogating the contribution of genetic variants in CHD and can be extended to other genetic diseases.
HostingRepository	PRIDE
AnnounceDate	2022-07-05
AnnouncementXML	Submission_2022-07-05_06:18:24.135.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ruth Huttenhain
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-20 01:15:23	ID requested
⏵ 1	2022-07-05 06:18:25	announced

Gonzalez-Teran B, Pittman M, Felix F, Thomas R, Richmond-Buccola D, H, ü, ttenhain R, Choudhary K, Moroni E, Costa MW, Huang Y, Padmanabhan A, Alexanian M, Lee CY, Maven BEJ, Samse-Knapp K, Morton SU, McGregor M, Gifford CA, Seidman JG, Seidman CE, Gelb BD, Colombo G, Conklin BR, Black BL, Bruneau BG, Krogan NJ, Pollard KS, Srivastava D, Transcription factor protein interactomes reveal genetic determinants in heart disease. Cell, 185(5):794-814.e30(2022) [pubmed]

submitter keyword: AP-MS, Congenital Heart Disease, Cardiomyocytes

Ruth Huttenhain
contact affiliation	Cellular and Molecular Pharmacology, UCSF, San Francisco, CA
contact email	ruth.huttenhain@ucsf.edu
lab head
Ruth Huttenhain
contact affiliation	UCSF
contact email	ruth.huttenhain@ucsf.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/07/PXD022091

PRIDE project URI

• PRIDE
  1. PXD022091
     1. Label: PRIDE project
     2. Name: Integration of Protein Interactome Data with Congenital Heart Disease Variants Reveals Disease Genes