Hospital Research Teams

The Adam Widman Lab

Overview

Adam Widman
Lab Head

The Widman lab within the Digital Oncology Program at MSKCC is using machine learning and genomics to engineer the next-generation of ultrasensitive, highly scalable liquid biopsies for early cancer detection, treatment monitoring, and detection of minimal residual disease (MRD) after surgery for early-stage cancer.

Liquid biopsy via circulating tumor DNA (ctDNA) offers the potential to serve as a critical biomarker in many settings within solid tumor oncology, such as the early detection of cancer, monitoring of treatment response (advanced disease, neoadjuvant, and adjuvant therapy settings), and detection of MRD after surgery. However, in many early-stage cancers and low volume treatment settings, ctDNA signal is sparsely diluted and thus difficult to detect among cell-free DNA (cfDNA) from noncancerous cells. Current ctDNA detection practices use deep targeted sequencing of a few informative sites such as patient-specific bespoke panels. These platforms are limited, as many commercial panels lack the sensitivity to reliably detect early-stage cancer that can be seen on imaging, much less low volume disease states like MRD. Further, the matched tissue requirement of many panels serves as a significant barrier to real world sensitivity, because patients often do not have matched tumor tissue available for analysis. Liquid biopsies are therefore not routinely used in many settings where they could be applicable, even at tertiary academic centers. For example, there are no FDA-approved liquid biopsy tests to monitor for MRD in solid tumors.

To overcome barriers to widespread use, we reasoned that the next generation of liquid biopsy tests would need to be 1) ultrasensitive, to detect and quantify tumor fraction (TF) in low-volume disease settings, and ii) tumor-naïve and highly scalable, to be deployed rapidly in all treatment settings where ultrasensitive liquid biopsy is needed. 

Our approach to liquid biopsy leverages advanced computational algorithms to extract sparse ctDNA signal from plasma whole genome sequencing (WGS). Plasma WGS is rapidly declining in cost and is highly scalable, as it can be run in virtually any genomics lab. WGS captures the breadth of cancer mutations (termed single nucleotide variants [SNVs]) and cancer aneuploidy (copy number variants [CNVs]), two important hallmarks of cancer that distinguish ctDNA from benign cfDNA. Our lab leverages novel deep learning strategies for detecting cancer mutations as well as data science and statistics methods to quantify anueploidy in cfDNA through a myriad of features including read-depth, B-allele frequency, and fragmentomics.

We are looking for highly motivated individuals with experience in machine learning and / or bioinformatics who want to make a sweeping impact on cancer detection and treatment monitoring. We are recruiting for technician, analyst, and software engineering roles. 
 

Publications

Widman A, Shah M, Frydendahl A, Halmos D, Khamnei CC, √ògaard N, Rajagopalan S, Arora A, Deshpande A, Hooper WF, Quentin J, Bass J, Zhang M, Langanay T, Andersen L, Steinsnyder Z, Liao W, Rasmussen MH, Henriksen TV, Jensen S√ò, Nors J, Therkildsen C, Sotelo J, Brand R, Schiffman JS, Shah RH, Cheng AP, Maher C, Spain L, Krause K, Frederick DT, den Brok W, Lohrisch C, Shenkier T, Simmons C, Villa D, Mungall AJ, Moore R, Zaikova E, Cerda V, Kong E, Lai D, Malbari MS, Marton M, Manaa D, Winterkorn L, Gelmon K, Callahan MK, Boland G, Potenski C, Wolchok JD, Saxena A, Turajlic S, Imielinski M, Berger MF, Aparicio S, Altorki NK, Postow MA, Robine N, Andersen CL, Landau DA. Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment. Nat Med. 2024 Jun;30(6):1655-1666. doi: 10.1038/s41591-024-03040-4. Epub 2024 Jun 14. PMID: 38877116; PMCID: PMC7616143.

Frydendahl A*, Widman A*, Øgaard N, Arora A, Halmos D, Nors J, Ahrenfeldt J, Henriksen TV, Demuth C, Raaby L, Rasmussen MH, Therkildsen C, Landau DA, Andersen CL. Whole-genome sequencing of cell-free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas. Mol Oncol. 2025 Jan 20. doi: 10.1002/1878-0261.13803. Epub ahead of print. PMID: 39831554.

Cheng AP*, Widman A*, Arora A*, et al. Whole genome error-corrected sequencing for sensitive circulating tumor DNA cancer monitoring. Nature Methods. In press

Widman A, Cohen B, Park V, McClure T, Wolchok J, Kamboj M. Immune-Related Adverse Events Among COVID-19-Vaccinated Patients With Cancer Receiving Immune Checkpoint Blockade. J Natl Compr Canc Netw. 2022 Oct;20(10):1134-1138. doi: 10.6004/jnccn.2022.7048. PMID: 36240845.

Bange EM, Han NA, Wileyto P, Kim JY, Gouma S, Robinson J, Greenplate AR, Hwee MA, Porterfield F, Owoyemi O, Naik K, Zheng C, Galantino M, Weisman AR, Ittner CAG, Kugler EM, Baxter AE, Oniyide O, Agyekum RS, Dunn TG, Jones TK, Giannini HM, Weirick ME, McAllister CM, Babady NE, Kumar A, Widman A, DeWolf S, Boutemine SR, Roberts C, Budzik KR, Tollett S, Wright C, Perloff T, Sun L, Mathew D, Giles JR, Oldridge DA, Wu JE, Alanio C, Adamski S, Garfall AL, Vella LA, Kerr SJ, Cohen JV, Oyer RA, Massa R, Maillard IP, Maxwell KN, Reilly JP, Maslak PG, Vonderheide RH, Wolchok JD, Hensley SE, Wherry EJ, Meyer NJ, DeMichele AM, Vardhana SA, Mamtani R, Huang AC. CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer. Nat Med. 2021 Jul;27(7):1280-1289. doi: 10.1038/s41591-021-01386-7. Epub 2021 May 20. PMID: 34017137; PMCID: PMC8291091.

View All Publications

People

Adam Widman

Lab Head

Affiliations

Achievements

  • Young Investigator Award, Melanoma Research Alliance (2023)
  • K08 Mentored Clinical Scientist Research Career Development Award, NCI (2023)
  • Innovation and Discovery Award, New York Genome Center (2022)
  • Young Investigator Award, Conquer Cancer Foundation (2020)
  • Young Investigator Abstract Award, Society for Immunotherapy for Cancer (2020)

Open Positions

To learn more about available postdoctoral opportunities, please visit our Career Center

Career Opportunities

Apply now

Get in Touch