Sema4 and Mount Sinai Use Integrative Network Analysis to
STAMFORD, Conn., Apr. 5, 2022 (GLOBE NEWSWIRE) — Sema4 (Nasdaq:SMFR), an artificial intelligence (AI)-powered platform for genomic and clinical data intelligence, and researchers from the Icahn School of Medicine at Mount Sinai (Icahn Mount Sinai) in New York, NY recently published a study in Nature Communications using network modeling to identify novel targets for the treatment of patients with early-stage invasive lung adenocarcinoma.
“This new paper demonstrates how the synergy of in silico, in vitro and in vivo technologies can accelerate the drug discovery process,” said Eric Schadt, PhD, founder and chief executive officer of Sema4 and author of the paper. “By conducting an integrative network analysis of early stage lung adenocarcinoma, together with our partners at Icahn Mount Sinai, we were able to identify a gene expression signature capable of stratifying patients for treatment and identifying a potential new therapeutic drug for these patients.”
“Approaches to diagnose and treat early-stage lung adenocarcinoma are evolving and based on advances in understanding the biology and clinical activities of these tumors,” said senior author Charles Powell, MD, MBA, Janice and Coleman Rabin Professor of Medicine and Chief of Pulmonary, Critical Care and Sleep Medicine at Icahn Mount Sinai. “Our work using novel network approaches in collaboration with Sema4 to identify signatures of invasiveness and to identify drugs that can intercept the progression of these cancers should help improve understanding and outcomes for this cancer.”
Lung adenocarcinoma is the most common lung cancer in the United States. Because of its often aggressive nature, early diagnosis is critical to improving survival. The new study unravels the molecular mechanisms underlying tumor invasion in early-stage lung adenocarcinoma to improve patient diagnosis, prognosis and treatment.
“Sema4’s advanced predictive modeling and data science expertise uniquely positions us to deliver value to and accelerate discovery for collaborators in the biopharma, healthcare and research worlds,” said Gustavo Stolovitzky, PhD, Chief Science Officer at Sema4. “Through this collaboration, we have once again proven the value of our integrative network modeling by discovering a new way to stratify early-stage lung adenocarcinomas into indolent and aggressive forms and by positing a potential therapeutic agent to help patients with the aggressive type. Depending on clinical validation, genomic testing for the invasive signature could one day be incorporated into our Sema4 Signal® portfolio of precision oncology solutions to help guide treatment decisions for patients with early stage aggressive lung adenocarcinoma.”
In the joint study building on the NIH-funded lung cancer research program in Dr. Powell, researchers at Icahn Mount Sinai collected early-stage lung adenocarcinoma tumor samples and determined their RNA. Sema4 then analyzed the network of gene-gene interactions based on this sequence data, resulting in the identification of a gene expression signature that can distinguish between invasive and non-invasive tumors.
“When we annotated the gene signature, we discovered an enrichment for genes associated with tumor-invasive functions,” said Jun Zhu, PhD, Head of Data Sciences at Sema4 and Professor of Genetics & Genomic Sciences at Icahn Mount Sinai (Dr. Zhu was the joint senior author on the paper). “We then analyzed retrospective patient data and defined a numerical index based on gene expression in the patients, which we called the ‘invasiveness score’. We found that this invasiveness score is strongly associated with survival in multiple independent cohorts, confirming its prognostic significance.”
Researchers at Icahn Mount Sinai showed that the invasiveness score is also strongly associated with invasiveness in cancer cell lines and validated it in a mouse model of early-stage lung adenocarcinoma. The integrative network analysis identified aurora kinases as key regulators of this invasiveness and suggested that they are good targets for the treatment of early-stage lung adenocarcinoma. Aurora kinases have known roles in tumor growth and survival in several other cancers, but this is the first confirmation of their role in early-stage lung cancer progression. Further experiments confirmed the expression of aurora kinases in tumors and found that their disruption by inhibitors reduced the invasive behavior in vitro. Similarly, the use of aurora kinase inhibitors in genetically engineered mice suppressed invasion and improved survival.
“This study, which combines the research and clinical expertise of Icahn Mount Sinai with Sema4’s advanced network modeling methods, is a textbook example of how in silico and experimental technologies can complement each other to accelerate research,” said Dr. powell. “We look forward to continuing this collaboration with Sema4 to further explore the therapeutic application of aurora kinase inhibitors in early-stage lung adenocarcinoma.”
The published study is based on technology developed by the Faculty of Mount Sinai. In addition to their roles at Sema4, Drs. Schadt and Zhu will continue to serve as part-time faculty at Icahn Mount Sinai. Mount Sinai and Mount Sinai faculty, including Drs. Schadt and Zhu have a financial interest in Sema4. Mount Sinai is also represented on Sema4’s board of directors.
Sema4 is a patient-centric health information company dedicated to advancing healthcare through data-driven insights. Sema4 is transforming healthcare by applying AI and machine learning to multidimensional, longitudinal clinical and genomic data to build dynamic models of human health and define optimal, individualized health pathways. Centrellis®, our innovative health information platform, enables us to generate a more complete understanding of disease and wellness and provide scientific solutions to the most pressing medical needs. Sema4 believes that patients should be treated as partners and data should be shared in the interest of all.
For more information, visit sema4.com and connect with Sema4 on Twitter, LinkedIn, Facebook and YouTube.
About Mount Sinai’s Health System
The Mount Sinai Health System is New York City’s largest academic medical system and includes eight hospitals, a premier medical school, and an extensive network of outpatient practices throughout the New York area. Mount Sinai advances medicine and health through unparalleled education and translational research and discovery to deliver care that is the safest, highest quality, most accessible, equitable, and best value of any health system in the nation. The health system includes approximately 7,300 primary care and specialty physicians; 13 joint venture outpatient surgical centers; more than 415 outpatient practices in the five boroughs of New York City, Westchester, Long Island and Florida; and more than 30 affiliated community health centers. Mount Sinai Hospital is on US News & World Report’s “Honor Roll” of the top 20 hospitals in the US and is the best in the country by specialty: No. 1 in geriatrics and top 20 in cardiology/heart surgery, diabetes /endocrinology, gastroenterology /GI surgery, neurology/Neurosurgery, orthopedics, pulmonology/lung surgery, rehabilitation and urology. New York Eye and Ear Infirmary of Mount Sinai ranks number 12 in ophthalmology. Mount Sinai Kravis Children’s Hospital is ranked in US News & World Report’s “Best Children’s Hospitals” and ranks among the best in the country in four of the 10 pediatric specialties. The Icahn School of Medicine is one of three medical schools that have distinguished based on multiple indicators: ranked in the top 20 of US News & World Report’s “Best Medical Schools”, in line with a US News & World Report “Honor Roll” Hospital, and No. 14 in the nation for funding from the National Institutes of Health. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five worldwide, and Mount Sinai Morningside in the top 20 worldwide.
For more information, visit https://www.mountsinai.org or search Mount Sinai on Facebook, Twitter, and YouTube.
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