Statistical thermodynamics of transcription profiles in normal development and tumorigeneses in cohorts of patients.
Experimental biology is providing the distribution of numerous different biological molecules inside cells and in body fluids of patients. Statistical methods of analysis have very successfully examined these rather large databases. We seek to use a thermodynamic analysis to provide a physical understanding and quantitative characterization of human cancers and other pathologies within a molecule-centered approach. The key technical development is the introduction of a Lagrangian. By imposing constraints the minimal value of the Lagrangian defines a thermodynamically stable state of the cellular system. The minimization also allows using experimental data measured at a number of different conditions to evaluate the steady-state distribution of biomolecules such as messenger RNAs. Thereby the number of effectively accessible quantum states of biomolecules is determined from the experimentally measured expression levels. With the increased resolution provided by the minimization of the Lagrangian one can differentiate between normal and diseased patients and further between disease subtypes. Each such refinement corresponds to imposing an additional constraint of biological origin. The constraints are the unbalanced ongoing biological processes in the system. MicroRNA expression level data for control and diseased lung cancer patients are analyzed as an example.
Département de Chimie, B6c, Université de Liège, B4000, Liège, Belgium.|The Fritz Haber Research Center for Molecular Dynamics, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
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The Fritz Haber Research Center for Molecular Dynamics, The Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel. rafi@chem.ucla.edu.|Crump Institute for Molecular Imaging, University of California Los Angeles, Los Angeles, CA, 900095, USA. rafi@chem.ucla.edu.|Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA. rafi@chem.ucla.edu.|Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA, 90095, USA. rafi@chem.ucla.edu.
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D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008957:Models, Genetic; D015233:Models, Statistical; D012333:RNA, Messenger / Q000235:genetics; D013816:Thermodynamics; D059467:Transcriptome
D035683:MicroRNAs; D012333:RNA, Messenger
Cancer heterogeneity; Genomics; Maximal entropy; Minimal free energy; Surprisal analysis; Systems biology