Multi-omic biomarker identification and validation for diagnosing warzone-related post-traumatic stress disorder.

Autor: Dean KR; Department of Systems Biology, Harvard University, Cambridge, MA, USA.; Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA., Hammamieh R; Integrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, Frederick, MD, USA., Mellon SH; Department of Obstetrics, Gynecology, & Reproductive Sciences, University of California, San Francisco, CA, USA., Abu-Amara D; Department of Psychiatry, New York Langone Medical School, New York, NY, USA., Flory JD; Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Guffanti G; Department of Psychiatry, McLean Hospital, Belmont, MA, USA., Wang K; Institute for Systems Biology, Seattle, WA, USA., Daigle BJ Jr; Departments of Biological Sciences and Computer Science, The University of Memphis, Memphis, TN, USA., Gautam A; Integrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, Frederick, MD, USA., Lee I; Institute for Systems Biology, Seattle, WA, USA., Yang R; Advanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Almli LM; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA., Bersani FS; Department of Psychiatry, University of California, San Francisco, CA, USA.; Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy., Chakraborty N; USACEHR, The Geneva Foundation, Frederick, MD, USA., Donohue D; USACEHR, The Geneva Foundation, Frederick, MD, USA., Kerley K; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA., Kim TK; Institute for Systems Biology, Seattle, WA, USA., Laska E; Department of Psychiatry, New York Langone Medical School, New York, NY, USA., Young Lee M; Institute for Systems Biology, Seattle, WA, USA., Lindqvist D; Department of Psychiatry, University of California, San Francisco, CA, USA.; Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Sweden., Lori A; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA., Lu L; Departments of Biological Sciences and Computer Science, The University of Memphis, Memphis, TN, USA., Misganaw B; Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA., Muhie S; USACEHR, The Geneva Foundation, Frederick, MD, USA., Newman J; Department of Psychiatry, New York Langone Medical School, New York, NY, USA., Price ND; Institute for Systems Biology, Seattle, WA, USA., Qin S; Institute for Systems Biology, Seattle, WA, USA., Reus VI; Department of Psychiatry, University of California, San Francisco, CA, USA., Siegel C; Department of Psychiatry, New York Langone Medical School, New York, NY, USA., Somvanshi PR; Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA., Thakur GS; Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA., Zhou Y; Institute for Systems Biology, Seattle, WA, USA., Hood L; Institute for Systems Biology, Seattle, WA, USA., Ressler KJ; Department of Psychiatry, McLean Hospital, Belmont, MA, USA., Wolkowitz OM; Department of Psychiatry, University of California, San Francisco, CA, USA., Yehuda R; Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY, USA.; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Jett M; Integrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, Frederick, MD, USA., Doyle FJ 3rd; Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA. frank_doyle@seas.harvard.edu., Marmar C; Department of Psychiatry, New York Langone Medical School, New York, NY, USA.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2020 Dec; Vol. 25 (12), pp. 3337-3349. Date of Electronic Publication: 2019 Sep 10.
DOI: 10.1038/s41380-019-0496-z
Abstrakt: Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using (1) data-driven methods, including Support Vector Machine with Recursive Feature Elimination and other standard or published methodologies, and (2) hypothesis-driven approaches, using previous genetic studies for polygenic risk, or other PTSD-related literature. After reassessment of ~30% of these participants, we refined this set of markers from 343 to 28, based on their performance and ability to track changes in phenotype over time. The final diagnostic panel of 28 features was validated in an independent cohort (26 cases, 26 controls) with good performance (AUC = 0.80, 81% accuracy, 85% sensitivity, and 77% specificity). The identification and validation of this diverse diagnostic panel represents a powerful and novel approach to improve accuracy and reduce bias in diagnosing combat-related PTSD.
Databáze: MEDLINE