# The joint WCM-NYGC Center for Functional and Clinical Interpretation of Tumor Profiles

> **NIH NIH U24** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $472,504

## Abstract

The Weill Cornell Medicine-New York Genome Center (WCM-NYGC) for Functional and Clinical
Interpretation of Tumor Profiles will perform integrative analyses of coding and non-coding variants to
detect and unravel the function of specific classes of mutations and assess their clinical potential. As
specified in the RFA, we have chosen to focus on two Core Competencies: (1) coding mutations and
(2) non-coding mutations (germline). We will use WCM’s expertise in clinical genomics demonstrated
by the first CLIA approved Whole Exome Sequencing test in New York State. We will leverage
NYGC’s computational infrastructure with > 5,000 cores and 10Pb storage and data management
expertise. We will focus our GDAC on specific classes of mutations: (1) coding mutations and their
clinical relevance including relevance to immunotherapy; (2) driver non-coding point mutations and
their role in transcriptional regulation; (3) the driving role of structural variations. In Aim 1 we will
annotate the clinical and functional impact of coding mutations including immunotherapy. First we will
generate a clinical grade report containing clinical interpretation of mutations, viewable through a
custom user interface. This will enable detailed statistics on number and frequency of clinically
relevant variants. A new module will help contribute new variants to the knowledge base and
community. Second, we will apply our analytical pipeline for unraveling the immune landscape
together with a novel integrative immunoscore that predicts which patients are more likely to respond
to immune checkpoint blockade, a therapy showing dramatic impact in a subset of cancer patients. In
Aim 2, we will annotate the driving role and impact of non-coding mutations on splicing. First, we will
functionally characterize genetic variants outside of genes (promoters, enhancers) using the
experimentally validated FunSeq pipeline. Second, we will analyze the transcriptional consequence of
splice site alterations using a novel for integrating RNA-Seq data with predicted splice-altering
variants from DNA sequencing. In Aim 3 we will annotate the driving role and transcriptional impact of
structural variations. We will annotate structural variants and gene fusions using a consensus-based
approach with methods benchmarked in our group as well as novel methods. The output of this Aim
will be comprehensive annotation and functional analysis of a critical class of non-coding events. In
summary, the proposed analyses rely on existing pipelines and tools that will be used in a standard
and automated way on the WCM-NYGC computational infrastructure. The objective of these analyses
is to derive novel knowledge and correlation that will impact both clinical and research cancer
genomics fields. The WCM-NYGC team will participate and be responsive to the cooperative partners
in this Network.

## Key facts

- **NIH application ID:** 9996510
- **Project number:** 5U24CA210989-05
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Olivier Elemento
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $472,504
- **Award type:** 5
- **Project period:** 2016-09-14 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996510

## Citation

> US National Institutes of Health, RePORTER application 9996510, The joint WCM-NYGC Center for Functional and Clinical Interpretation of Tumor Profiles (5U24CA210989-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9996510. Licensed CC0.

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