# Next-generation Functional Genetic Screening of Un-screenable Traits

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $1,051,170

## Abstract

Project Summary/Abstract
 With the rapid advances in DNA sequencing, we now have a near-complete human genome, a fairly
comprehensive catalog of germline and somatic variants, as well as rich annotations of functional genomic
elements. The next challenge in the field is to obtain a complete functional annotation of genetic variants and
genomic elements at the cellular and organismal levels. Genome editing technology, in particularly the
CRISPR/Cas9 system, has allowed rapid and precise modifications of the genome and connecting of these to
functional outcomes. However, all current high-throughput screening approaches rely on phenotypes that can
be coupled to cell survival, cell imaging, fluorescent cell sorting, or affinity enrichments. Genetic variants that
have more subtle phenotypic consequences, which might represent the majority, are not amenable to such
screens. Furthermore, screening of natural genetic variation via assaying of individual cell lines under in vitro
culture conditions also has limited throughput and might miss functional differences that depend on specific
physiological contexts. In this project we seek to develop a next-generation functional genetic screening
method that can overcome these current limitations. Utilizing induced pluripotent stem cell differentiation as an
exemplar model system, we will develop and demonstrate our integrated experimental and computational
methodology to enable comprehensive and en masse functional screening of coding and non-coding genomic
elements. We expect our platform will greatly accelerate the functional annotation of genetic variants, including
many variants of unknown significance, across various normal and diseased cell types and tissues.

## Key facts

- **NIH application ID:** 9978854
- **Project number:** 5R01HG009285-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Prashant Mali
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,051,170
- **Award type:** 5
- **Project period:** 2017-08-25 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978854

## Citation

> US National Institutes of Health, RePORTER application 9978854, Next-generation Functional Genetic Screening of Un-screenable Traits (5R01HG009285-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9978854. Licensed CC0.

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