[2][3] Schadt has also worked to engage the public, encouraging people to participate in scientific research and helping them understand privacy concerns around DNA-based information.

While completing his PhD, Schadt joined Roche Bioscience in 1998 as a senior research scientist and began his work on DNA microarrays, designing novel algorithms to process and interpret these data.

[8] In 1999, after becoming acquainted with Stephen Friend, he was hired as chief scientist at Rosetta Inpharmatics, a startup biotech company focused on the generation and analysis of high-dimensional functional genomics data.

[2] Demonstrating the ability to infer causal relationships among features in high dimensional data using DNA variation information, Schadt and his colleagues at Merck began reconstructing predictive networks that were shown to be causally associated with disease,[11] [12] [13] [14] [15] leading to the idea of targeting networks, not single genes, to effectively treat common disorders such as Alzheimer's disease, obesity, and most forms of cancer.

[1] In 2009, along with Stephen Friend, Schadt founded Sage Bionetworks,[3] a nonprofit organization with the goal of encouraging collaboration between academic and commercial scientists in performing network-based studies of disease and making the data publicly available.

[20] He also demonstrated the ability to infer epigenetic changes from the sequencing data, uncovering novel regulatory mechanisms that may impact pathogenicity and virulence of bacteria of concern in public health.

Schadt's team was cited as the reason the Icahn School of Medicine at Mount Sinai was named #5 of the top 10 most innovative organizations in big data by Fast Company in a 2014 ranking.

[33] The project intended to perform genotyping on as many as 1 million people to find protective biological mechanisms that prevent disease-causing genetic mutations from becoming active.

[34][35] Based on an analysis of publicly available data, scientists in the Resilience Project estimated that one person in 15,000 has a protective mechanism preventing activity of disease-causing genetic variants.

[36] The project led to a paper published in 2016 in Nature Biotechnology, reporting the analysis of nearly 600,000 genomes and the identification of individuals resilient to severe Mendelian childhood diseases.