TOPMed

Overview

The Trans-Omics for Precision Medicine (TOPMed) program, sponsored by the National Institutes of Health (NIH) National Heart, Lung and Blood Institute (NHLBI), is part of a broader Precision Medicine Initiative, which aims to provide disease treatments tailored to an individual’s unique genes and environment. TOPMed contributes to this Initiative through the integration of whole-genome sequencing (WGS) and other omics (e.g., metabolic profiles, epigenomics, protein and RNA expression patterns) data with molecular, behavioral, imaging, environmental, and clinical data.

Publication

Kowalski, M.H., Qian, H., Hou, Z., Rosen, J.D., Tapia, A.L., Shan, Y., Jain, D., Argos, M., Arnett, D.K., Avery, C. and Barnes, K.C., 2019. Use of> 100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations. PLoS genetics, 15(12), p.e1008500.

VCF extraction

We currently extract the following fields from TOPMed VCF file:

##INFO=<ID=AN,Number=1,Type=Integer,Description="Number of Alleles in Samples with Coverage">
##INFO=<ID=AC,Number=A,Type=Integer,Description="Alternate Allele Counts in Samples with Coverage">
##INFO=<ID=AF,Number=A,Type=Float,Description="Alternate Allele Frequencies">
##INFO=<ID=Het,Number=A,Type=Integer,Description="Number of samples with heterozygous genotype calls">
##INFO=<ID=Hom,Number=A,Type=Integer,Description="Number of samples with homozygous alternate genotype calls">

Example:

chr1    10132   TOPMed_freeze_5?chr1:10,132     T       C       255     SVM     VRT=1;NS=62784;AN=125568;AC=32;AF=0.000254842;Het=32;Hom=0      NA:FRQ  125568:0.000254842

GRCh37 liftover

The data is not available for GRCh37 on TOPMed website. We performed a liftover from GRCh38 to GRCh37 using dbSNP ids.

Download URL

https://bravo.sph.umich.edu/freeze5/hg38/download

JSON output

"topmed":{ 
   "allAc":20,
   "allAn":125568,
   "allAf":0.000159,
   "allHc":0,
   "failedFilter":true
}

Field	Type	Notes
allAc	int	TOPMed allele count
allAn	int	TOPMed allele number. Non-zero integer.
allAf	float	TOPMed allele frequency (computed by Illumina Connected Annotations)
allHc	int	TOPMed homozygous count
failedFilter	bool	True if this variant failed any filters