Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

In Vitro Toxicity Testing at Massive Scale in Diverse Primary Human Cells

Award Number: R44ES032515
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2025

Group Awards By:

View Award Description

In Vitro Toxicity Testing at Massive Scale in Diverse Primary Human Cells - PROJECT SUMMARY—Coral Genomics is combining whole genome sequencing and RNA profiling in cell- based functional assays to predict human variation in the metabolism and toxicity of compounds encountered in therapeutic and environmental exposures. RNA profiling before and after exposure provides a high-dimensional representation of changes in cell function, and the use of rapid, cost-effective profiling could enable toxicity testing in large, diverse panels of human cells. Thus, to address the need for toxicity testing that better reflects the genetic diversity of human populations, Coral developed innovative approaches to reduce the cost and increase the speed of high-throughput sequencing assays. In a successful Phase I SBIR (R43 HG010445), Coral established protocols for cost-effective sample multiplexing for rapid shallow sequencing of samples, developed a re-indexing workflow to pool samples into a single sequencing run, and combined streamlined sequencing solutions with novel functional assays and algorithms to improve the performance of polygenic risk scores (PRS). In a collaboration with the US Food and Drug Administration (FDA), Coral applied these techniques to predict patient-specific hepatocyte response profiles to acetaminophen (N = 200) and found significant interindividual variability in toxicity. Importantly, the findings show that a patient’s genotype predicts a significant portion (AUC = 0.85) of the interindividual variation, indicating the approach is sensitive to genetic diversity. Preliminary findings indicate Coral’s approach may be a sensitive means for identifying differences in toxic responses to compounds across diverse populations. Further development and testing across multiple compounds in a large, diverse sample has the potential to provide a scalable, high-throughput platform for effective toxicity testing that is more representative of the diversity of human responses. Coral proposes a Direct to Phase II SBIR in response to NIEHS’s RFA-ES-20-208 to evaluate these methods in three cell models and advance at least one model to full-scale testing with 250 patient samples and 100 compounds with known toxicity profiles. Aim 1. Characterize the interindividual variability of RNA profile shifts in three human cell models (i.e., immune, hepatocyte, and embryoid body) exposed to ten compounds with known toxicity profiles. Select Milestones: 1) 4,500 response profiles; 2) Statistical significance of intraindividual variability vs. interindividual variability (p<0.001); 3) ≥ 50% of differentially expressed genes associated with exposure observable with < 1 million reads; 4) R2 > 0.3 for FAERS profile and AUC > 0.85 for Tox21 dataset. Aim 2. Using the most predictive cell model, characterize interindividual variability of sublethal cytotoxic responses to 100 compounds with known toxicity profiles to develop a robust model for predicting systemic toxicity. Select Milestones: 1) 75,000 response profiles; 2) Identification of ≥ 5 compounds with high population level variability in toxicity (1-50th percentile variation >10); 3) R2 > 0.4 using chemical and transcriptional data to predict FAERS profile; 5) R2 at predicting toxicity profile of an individual across 100 compounds > 0.5.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$623,807 )
2025	2023	GORDIAN BIOTECHNOLOGY, INC.	486 CABOT RD	SOUTH SAN FRANCISCO	CA	94080	SAN MATEO	USA	Environmental Health	001	2	5/9/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$623,807
2025	2021	CORAL GENOMICS, INC.	953 INDIANA ST	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Environmental Health	000	1	1/14/2025	NEW	$0
														Subtotal = -$623,807

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	GORDIAN BIOTECHNOLOGY, INC.	486 CABOT RD	SOUTH SAN FRANCISCO	CA	94080	SAN MATEO	USA	Environmental Health	000	2	3/15/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2023	GORDIAN BIOTECHNOLOGY, INC.	486 CABOT RD	SOUTH SAN FRANCISCO	CA	94080	SAN MATEO	USA	Environmental Health	001	2	4/15/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $811,373 )
2023	2023	GORDIAN BIOTECHNOLOGY, INC.	486 CABOT RD	SOUTH SAN FRANCISCO	CA	94080	SAN MATEO	USA	Environmental Health	001	2	8/28/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$811,373
2023	2021	CORAL GENOMICS, INC.	953 INDIANA ST	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Environmental Health	000	1	8/28/2023	NEW	$0
														Subtotal = $811,373

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	CORAL GENOMICS, INC.	953 INDIANA ST	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Environmental Health	000	1	1/28/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $811,373 )
2021	2021	CORAL GENOMICS, INC.	953 INDIANA ST	SAN FRANCISCO	CA	94107	SAN FRANCISCO	USA	Environmental Health	000	1	1/28/2021	NEW	$811,373
														Subtotal = $811,373

Grand Total All Awards = $998,939

Top

All Categories

About

Search

Reports

Data Submission

Award Information

In Vitro Toxicity Testing at Massive Scale in Diverse Primary Human Cells

Award Number: R44ES032515

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer