Icahn Institute for Genomics and Multiscale Biology

Icahn Institute for Genomics and Multiscale Biology
Established	2011
Research type	Translational research
Field of research	Systems biology, Integrative biology, Computational biology, multiscale biology
Director	Eric Schadt
Address	1425 Madison Avenue, New York, NY 10029-6501
Location	New York, NY
Affiliations	Icahn School of Medicine at Mount Sinai Mount Sinai Hospital, New York
Website	http://icahn.mssm.edu/genomics

The Icahn Institute for Genomics and Multiscale Biology is a biomedical and genomics research institute located in New York, NY. It is housed within the Icahn School of Medicine at Mount Sinai. Its aim is to generate and integrate many layers of biological, clinical, and environmental data in order to characterize and understand complex human diseases on a network level, and to use that data to advance information-driven medicine and to better diagnose and treat patients at Mount Sinai Hospital, New York and elsewhere.^[1]

Goals

The institute’s primary goal is to improve patient care by building predictive models to better characterize disease. These models are constructed with multiple layers of biological data, including gene expression, metabolite, DNA, and protein information, and are combined with phenotypic and clinical data, predictive modeling, and probabilistic analysis to try to elucidate the complex mechanisms of disease.^[2] This concept is called multiscale biology. To achieve this goal, scientists at the Icahn Institute for Genomics and Multiscale Biology have outfitted facilities such as the Genomics Core with new technologies to generate many types of biological information and have placed an emphasis on hiring staff with bioinformatics expertise to analyze big data.^[3] Institute director Eric Schadt has said that this approach — along with the institute’s connection to both a hospital and medical school — is expected to lead to improved and more personalized diagnoses, assessments of risk, and treatment plans for patients.^[1]

History

The institute was formed in 2011. Eric Schadt was named as founding director of the new institute.^[2]

The Icahn Institute for Genomics and Multiscale Biology is slated to receive more than $100 million in funding in its first several years, allocated from a $1 billion capital campaign run by Mount Sinai School of Medicine.^[2]

Originally called the Institute for Genomics and Multiscale Biology, it was renamed in 2012 when philanthropist Carl Icahn pledged $200 million to its parent organization, the Icahn School of Medicine at Mount Sinai.^[4]

In 2012, the Icahn Institute for Genomics and Multiscale Biology received certification for the first CLIA-approved next-generation sequencing lab in New York City.^[1]^[3]

Institute faculty Andrew Kasarskis, Michael Linderman, George Diaz, Ali Bashir, and Randi Zinberg taught the first class in which Mount Sinai medical students were able to fully sequence and analyze their own genomes.^[5]

Institute member Joel Dudley was named one of the 100 most creative people in business in a 2014 list compiled by Fast Company.^[6] The magazine said it chose Dudley "for splicing information with quality medical care."

In 2014 the institute, in collaboration with Sage Bionetworks, announced a new project aiming to genotype up to 1 million people with the goal of identifying the rare biological mechanisms that keep people healthy when they have genetic variants that should cause disease.^[7]^[8] The Resilience Project will scan the genomes of healthy people age 30 and older who contribute their DNA to the effort with an initial focus on 127 diseases. Scientists anticipate that finding protective mechanisms for Mendelian diseases will be more straightforward than finding ones for complex or multifactorial diseases.^[9]^[10] Based on an analysis of publicly available data from 600,000 human genomes, scientists involved in the Resilience Project estimate that one person in 15,000 has a mechanism protecting against disease-causing genetic variants.^[11]

Research

Research at the institute falls into six broad disease areas:^[12]

Scientists from the institute published a paper in Nature Genetics in 2012 demonstrating the ability to derive enough information from non-DNA sources to identify individuals whose supposedly anonymized biological data is stored in large research databases.^[13] The authors reported that measuring RNA levels in tissue allowed them to infer a genetic barcode that could be used to match other materials to that same individual. This was noteworthy as validation of existing concerns among genomics scientists that it may not be possible to prevent the identification of an individual from genetic data even when that data is meant to be anonymous.

In a PLoS Biology paper, institute director Eric Schadt led a research team that utilized six different types of data (metabolite concentration, gene expression, DNA variation, DNA-protein binding, protein-metabolite interaction, and protein-protein interaction) to reconstruct networks involved in cell regulation.^[14]

Data scientist Jeffrey Hammerbacher from Cloudera joined the institute in 2012 as an assistant professor. In an interview with Charlie Rose he said that his goal is to establish scalable infrastructure for data storage and analysis and to use that foundation to integrate genomic data with existing health records and improve the quality of health care.^[15]

In 2013, institute scientists published a paper in the journal Cell reporting findings from a network-based study of late-onset Alzheimer's disease. The researchers constructed gene regulatory networks and discovered a neural structure involved in a pathway associated with onset of the disease.^[16]

The institute has established a research program to use predictive network modeling for personalized cancer therapy. Scientists in the program combine DNA, RNA, copy number variation, and other data from individual patients, and test some of the detected mutations in fly models. The goal is to find the driver mutations of each patient’s data and recommend specific treatments based on that information. By March 2013, the program had worked on seven cases with more planned.^[17] One of the cases, that of Stephanie Lee, was publicized in an article in Esquire reporting on how the scientists implanted tumor cells into a fly and then found an existing medication that knocked out the tumor in the models.^[18]^[19]

Similarly, the institute will work with Mount Sinai’s rare disorder clinic to study how single-gene diseases interact with other biomolecular processes by measuring and analyzing molecular, cellular, and tissue networks along with environmental response information.^[1]

In January 2014, scientists from the institute’s Division of Psychiatric Genomics including Pamela Sklar published two papers in the journal Nature that explored the genetic complexity of schizophrenia.^[20]^[21] The exome sequencing studies of populations in Bulgaria and Sweden revealed that the disorder is likely caused by a lot of rare genetic mutations rather than a few common mutations.^[22]^[23] The projects also established the world’s largest database on schizophrenia.

Leadership

The leadership of the Icahn Institute for Genomics and Multiscale Biology, as listed on its website, includes:

Director: Eric Schadt
Co-Director: Andrew Kasarskis

References

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