Goldfinch Bio Presents Methods to Mitigate Batch Effects in Whole Genome Sequencing Samples at ASHG 2019 Annual Meeting

Oct. 21, 2019 11:00 UTC

Data-driven approach enables well-calibrated dataset for case-control genome-wide association study in the Kidney Genome Atlas

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Goldfinch Bio, a U.S.-based, clinical stage biotechnology company focused on discovering and developing precision medicines for the treatment of kidney diseases, announced a novel computational approach applied to its proprietary Kidney Genome Atlas (KGA) to enable a well-calibrated dataset for case-controlled genomic-wide association studies (GWAS) in focal segmental glomerulosclerosis (FSGS). These methods were described in an oral presentation on October 19th at the American Society of Human Genetics (ASHG) 2019 Annual Meeting in Houston, TX.

“In the field, the integration of whole genome sequencing samples from many sources presents an ongoing quality control challenge because of batch effects that lead to inflation in test statistics, or false positives, when identifying the location of specific genetic targets,” said Anthony Johnson, M.D., President and Chief Executive Officer of Goldfinch Bio. “The data presented at ASHG validate our approach to combating technical artifacts across very large data sets by deriving covariates from the data and carefully filtering control samples. As a result, the proprietary Kidney Genome Atlas that Goldfinch Bio has developed enables the analysis of federated datasets from multiple centers to increase statistical power to identify appropriate targets for potential kidney disease treatments.”

Researchers utilized the KGA, which currently contains whole genome sequencing (WGS) on 23,000 de-identified individual patients, including 2,000 cases of FSGS and other proteinuric disorders, to discover loci associated with FSGS, a disease that causes scarring of the kidney which can lead to kidney failure. The researchers sourced cases and controls from five clinical sites and 21 publicly-available cohort studies. The heterogeneity in sample acquisition presented challenges for downstream analysis, as evidenced by massive inflation in test statistics when standard filtering and quality control methods were applied. Notably, the data revealed a batch effect confounded with case/control status.

Researchers then implemented a three-pronged data-driven approach to further determine and control for batch effects: identifying clusters of similar sequencing technologies by conducting a principal component analysis on depth of coverage; implementing a novel use of silhouette scores and permutations to quantify case-control dissimilarity at the dataset-level; and iteratively removing controls with high dissimilarity from cases to achieve a better-calibrated dataset for case-control GWAS.

A preliminary, proof-of-principle analysis in a subset of individuals showed that inflation was well controlled. After confirming the statistical associations, researchers will link the signals to specific genes to identify putative targets for therapeutic intervention.

A copy of the abstract, entitled Mitigating Batch Effects in >23,000 WGS Samples for a Case-Control GWAS of Kidney Disease, is available on the Goldfinch Bio corporate website at

About the Kidney Genome AtlasTM

Goldfinch Bio’s Kidney Genome Atlas is the most comprehensive patient registry to investigate the underlying mechanisms of kidney disease. Through the combination of genomic, transcriptomic and proteomic data with thousands of anonymized clinical patient profiles, Goldfinch Bio is able to conduct unprecedented analyses to elucidate pathways and novel targets for kidney disease.

In May 2019, Goldfinch Bio entered into a strategic collaboration with Gilead Sciences, Inc. to sequence 80,000 diabetic kidney disease (DKD) patients and diabetic controls. Goldfinch Bio received a $55 million upfront payment, including a $5 million equity investment, and a commitment of an additional $54 million to support the development of the KGA platform for DKD. Goldfinch Bio will validate targets and support discovery and development of products to which Gilead will have exclusive option rights in exchange for additional milestone payments.

About Goldfinch Bio

Goldfinch Bio, Inc. is a clinical stage biotechnology company that leverages a genomics-based, precision medicine approach to discovering and developing kidney disease treatments. Its Kidney Genome Atlas™ is a proprietary biology platform that drives candidate discovery, patient selection and biomarker development. The Company’s lead candidate, GFB-887, is a subtype-selective, small molecule TRPC5 being evaluated in a Phase 1 clinical trial for the treatment of kidney diseases. Goldfinch Bio, headquartered in Cambridge, Massachusetts, was launched in 2016 by Third Rock Ventures and has an established strategic collaboration with Gilead Sciences, Inc. For more information about Goldfinch Bio, visit

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Goldfinch Bio:
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David Rosen, 212-600-1902

Source: Goldfinch Bio, Inc.

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