Random Forests Are Able to Identify Differences in Clotting Dynamics from Kinetic Models of Thrombin Generation.

Jayavel Arumugam, Satish T S Bukkapatnam, Krishna R Narayanan, Arun R Srinivasa
Author Information
  1. Jayavel Arumugam: Department of Mechanical Engineering, Texas A&M University, College Station, Texas, United States of America.
  2. Satish T S Bukkapatnam: Department of Industrial and Systems Engineering, Texas A&M University, College Station, Texas, United States of America.
  3. Krishna R Narayanan: Department of Electrical and Computer Engineering, Texas A&M University, College Station, Texas, United States of America.
  4. Arun R Srinivasa: Department of Mechanical Engineering, Texas A&M University, College Station, Texas, United States of America.

Abstract

Current methods for distinguishing acute coronary syndromes such as heart attack from stable coronary artery disease, based on the kinetics of thrombin formation, have been limited to evaluating sensitivity of well-established chemical species (e.g., thrombin) using simple quantifiers of their concentration profiles (e.g., maximum level of thrombin concentration, area under the thrombin concentration versus time curve). In order to get an improved classifier, we use a 34-protein factor clotting cascade model and convert the simulation data into a high-dimensional representation (about 19000 features) using a piecewise cubic polynomial fit. Then, we systematically find plausible assays to effectively gauge changes in acute coronary syndrome/coronary artery disease populations by introducing a statistical learning technique called Random Forests. We find that differences associated with acute coronary syndromes emerge in combinations of a handful of features. For instance, concentrations of 3 chemical species, namely, active alpha-thrombin, tissue factor-factor VIIa-factor Xa ternary complex, and intrinsic tenase complex with factor X, at specific time windows, could be used to classify acute coronary syndromes to an accuracy of about 87.2%. Such a combination could be used to efficiently assay the coagulation system.

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MeSH Term

Acute Coronary Syndrome
Algorithms
Blood Coagulation
Blood Coagulation Factors
Coronary Artery Disease
Decision Trees
Humans
Kinetics
Models, Biological
Molecular Dynamics Simulation
Thrombin
Thromboplastin
Time Factors

Chemicals

Blood Coagulation Factors
Thromboplastin
Thrombin

Word Cloud

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