Overview for Researchers

The overarching goal of iGeneTRAiN is to assemble and deeply integrate highly characterized solid-organ transplant phenotypes with genomic and other omic datasets, and transitions to translational research for early detection of pre and post-transplant complications. iGeneTRAIN is currently progressing through three phases shown below
Phase 1: Phase 1 has largely been organizational, focusing on maximizing the existing data for genome-wide association studies (GWAS) of transplant related phenotypes, from consortium members. Under Phase 1, we have, and continue to, assemble phenotypic and genetic data from existing solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) studies. For clinical phenotyping datasets, we have been collating and harmonizing phenotype measures that that are being used in additional analyses (Phase 2). For genetic datasets, we have collated information from different genetic datasets, creating a comprehensive catalog of biomarkers derived from 1) genome-wide genotyping and 2) second generation sequencing (SGS) for genome-wide association studies (GWAS) and 3) copy number variant (CNV) and candidate gene studies for primary/end-stage disease studies. Ultimately, this is facilitating data meta-analyses and replication studies across the consortium.
Phase 1a (completed for the majority of existing studies): Surveying and collating the relevant covariate, phenotypic and outcome data information among existing and pending studies across various sites and organ procurement organizations. Phase I studies can also include DNA-only studies which are being leveraged in replication studies and in new SGS and GWG studies, some of which are funded through NIH and Industry sponsorship. 
Phase 1b: Formed phenotype-specific working groups. These primarily include four groups focused on solid organ transplant (heart, kidney and liver) with small numbers of hematopoietic stem cell transplant datasets aggregated to date. Respective groups focused on collating, harmonization and formatting of relevant phenotypes and covariates for analyses.
Phase 1c: Formation of four additional working groups whose interests intersect across different transplant phenotypes. These groups are:
  • HLA working group
  • Genomic and multiomics groups 
  • Pharmacogenomics
  • Steering committee (comprised of representative’s various workgroups).

Phase 2 has been building upon existing single-site and initial meta-analyses and conducting broader meta-analyses studies across additional iGeneTRAIN single-organ and cross-organ studies. These have been completed for a number of solid-organ specific, and cross-organ specific analyses. We have embarked on additional RNA expression, proteomic, and functional studies using biological materials collected from the respective studies. These have been performed to data on a number of NIH funded studies including A-WISH, A2ALL, BioTIP, CTOT-03 and a number of national and international heart transplant studies). 
Phase 3, entails deeper harmonization of the consortium’s activities (once the majority of the single site publications have been completed) and establishing long-term sustainability through large national and international grants (a number of which have recently been awarded through NIAID/NIH), and with Industry collaborations.
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