Literature DB >> 30681362

Deep Reinforcement Learning and Simulation as a Path Toward Precision Medicine.

Brenden K Petersen1, Jiachen Yang1, Will S Grathwohl1, Chase Cockrell2, Claudio Santiago1, Gary An2, Daniel M Faissol1.   

Abstract

Traditionally, precision medicine involves classifying patients to identify subpopulations that respond favorably to specific therapeutics. We pose precision medicine as a dynamic feedback control problem, where treatment administered to a patient is guided by measurements taken during the course of treatment. We consider sepsis, a life-threatening condition in which dysregulation of the immune system causes tissue damage. We leverage an existing simulation of the innate immune response to infection and apply deep reinforcement learning (DRL) to discover an adaptive personalized treatment policy that specifies effective multicytokine therapy to simulated sepsis patients based on systemic measurements. The learned policy achieves a dramatic reduction in mortality rate over a set of 500 simulated patients relative to standalone antibiotic therapy. Advantages of our approach are threefold: (1) the use of simulation allows exploring therapeutic strategies beyond clinical practice and available data, (2) advances in DRL accommodate learning complex therapeutic strategies for complex biological systems, and (3) optimized treatments respond to a patient's individual disease progression over time, therefore, capturing both differences across patients and the inherent randomness of disease progression within a single patient. We hope that this work motivates both considering adaptive personalized multicytokine mediation therapy for sepsis and exploiting simulation with DRL for precision medicine more broadly.

Entities:  

Keywords:  agent-based model; deep reinforcement learning; precision medicine; sepsis.

Mesh:

Year:  2019        PMID: 30681362      PMCID: PMC6590719          DOI: 10.1089/cmb.2018.0168

Source DB:  PubMed          Journal:  J Comput Biol        ISSN: 1066-5277            Impact factor:   1.479


  17 in total

1.  Clinical trials of mediator-directed therapy in sepsis: what have we learned?

Authors:  J C Marshall
Journal:  Intensive Care Med       Date:  2000       Impact factor: 17.440

2.  Development of a three-dimensional multiscale agent-based tumor model: simulating gene-protein interaction profiles, cell phenotypes and multicellular patterns in brain cancer.

Authors:  Le Zhang; Chaitanya A Athale; Thomas S Deisboeck
Journal:  J Theor Biol       Date:  2006-07-27       Impact factor: 2.691

3.  In silico experiments of existing and hypothetical cytokine-directed clinical trials using agent-based modeling.

Authors:  Gary An
Journal:  Crit Care Med       Date:  2004-10       Impact factor: 7.598

4.  Multi-cell agent-based simulation of the microvasculature to study the dynamics of circulating inflammatory cell trafficking.

Authors:  Alexander M Bailey; Bryan C Thorne; Shayn M Peirce
Journal:  Ann Biomed Eng       Date:  2007-04-10       Impact factor: 3.934

5.  An enhanced agent based model of the immune system response.

Authors:  V Baldazzi; F Castiglione; M Bernaschi
Journal:  Cell Immunol       Date:  2007-04-09       Impact factor: 4.868

Review 6.  Agent-based models in translational systems biology.

Authors:  Gary An; Qi Mi; Joyeeta Dutta-Moscato; Yoram Vodovotz
Journal:  Wiley Interdiscip Rev Syst Biol Med       Date:  2009 Sep-Oct

7.  The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated protein C?*.

Authors:  Steven M Opal; R Phillip Dellinger; Jean-Louis Vincent; Henry Masur; Derek C Angus
Journal:  Crit Care Med       Date:  2014-07       Impact factor: 7.598

8.  Agent-based modeling of host-pathogen systems: The successes and challenges.

Authors:  Amy L Bauer; Catherine A A Beauchemin; Alan S Perelson
Journal:  Inf Sci (N Y)       Date:  2009-04-29       Impact factor: 6.795

Review 9.  Pharmacoeconomic implications of new therapies in sepsis.

Authors:  Kelly A Wood; Derek C Angus
Journal:  Pharmacoeconomics       Date:  2004       Impact factor: 4.981

Review 10.  Agent-based modeling: a systematic assessment of use cases and requirements for enhancing pharmaceutical research and development productivity.

Authors:  C Anthony Hunt; Ryan C Kennedy; Sean H J Kim; Glen E P Ropella
Journal:  Wiley Interdiscip Rev Syst Biol Med       Date:  2013-06-04
View more
  9 in total

Review 1.  High-dimensional role of AI and machine learning in cancer research.

Authors:  Enrico Capobianco
Journal:  Br J Cancer       Date:  2022-01-10       Impact factor: 9.075

2.  Agent-Based Modeling of Systemic Inflammation: A Pathway Toward Controlling Sepsis.

Authors:  Gary An; R Chase Cockrell
Journal:  Methods Mol Biol       Date:  2021

3.  An Introduction to Machine Learning Approaches for Biomedical Research.

Authors:  Juan Jovel; Russell Greiner
Journal:  Front Med (Lausanne)       Date:  2021-12-16

4.  Comparative Computational Modeling of the Bat and Human Immune Response to Viral Infection with the Comparative Biology Immune Agent Based Model.

Authors:  Chase Cockrell; Gary An
Journal:  Viruses       Date:  2021-08-16       Impact factor: 5.048

5.  Supporting Computational Apprenticeship Through Educational and Software Infrastructure: A Case Study in a Mathematical Oncology Research Lab.

Authors:  Aasakiran Madamanchi; Madison Thomas; Alejandra Magana; Randy Heiland; Paul Macklin
Journal:  PRIMUS (Terre Ht)       Date:  2021-02-18

6.  Preparing for the next COVID: Deep Reinforcement Learning trained Artificial Intelligence discovery of multi-modal immunomodulatory control of systemic inflammation in the absence of effective anti-microbials.

Authors:  Dale Larie; Gary An; Chase Cockrell
Journal:  bioRxiv       Date:  2022-02-18

7.  Drug Development Digital Twins for Drug Discovery, Testing and Repurposing: A Schema for Requirements and Development.

Authors:  Gary An; Chase Cockrell
Journal:  Front Syst Biol       Date:  2022-06-20

Review 8.  Artificial intelligence and its impact on the domains of universal health coverage, health emergencies and health promotion: An overview of systematic reviews.

Authors:  Antonio Martinez-Millana; Aida Saez-Saez; Roberto Tornero-Costa; Natasha Azzopardi-Muscat; Vicente Traver; David Novillo-Ortiz
Journal:  Int J Med Inform       Date:  2022-08-17       Impact factor: 4.730

9.  Utilizing the Heterogeneity of Clinical Data for Model Refinement and Rule Discovery Through the Application of Genetic Algorithms to Calibrate a High-Dimensional Agent-Based Model of Systemic Inflammation.

Authors:  Chase Cockrell; Gary An
Journal:  Front Physiol       Date:  2021-05-19       Impact factor: 4.566

  9 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.