title: Estimation of Heterogeneity in Diagnostic Parameters of Age-related Diseases.
abstract: The heterogeneity of parameters is a ubiquitous biological phenomenon, with critical implications for biological systems functioning in normal and diseased states. We developed a method to estimate the level of objects set heterogeneity with reference to particular parameters and applied it to type II diabetes and heart disease, as examples of age-related systemic dysfunctions. The Friedman test was used to establish the existence of heterogeneity. The Newman-Keuls multiple comparison method was used to determine clusters. The normalized Shannon entropy was used to provide the quantitative evaluation of heterogeneity. There was obtained an estimate for the heterogeneity of the diagnostic parameters in healthy subjects, as well as in heart disease and type II diabetes patients, which was strongly related to their age. With aging, as with the diseases, the level of heterogeneity (entropy) was reduced, indicating a formal analogy between these phenomena. The similarity of the patterns in aging and disease suggested a kind of "early aging" of the diseased subjects, or alternatively a "disease-like" aging process, with reference to these particular parameters. The proposed method and its validation on the chronic age-related disease samples may support a way toward a formal mathematical relation between aging and chronic diseases and a formal definition of aging and disease, as determined by particular heterogeneity (entropy) changes.
authors.affiliation: C.D. Technologies Ltd., Israel.
authors.forename: David
authors.initials: D
authors.lastname: Blokh
authors.affiliation: Department of Science, Technology and Society, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Ilia
authors.initials: I
authors.lastname: Stambler
keywords: Friedman test; Newman-Keuls method; age related disease; aging; diabetes; heart disease; normalized Shannon entropy; parameter heterogeneity; system complexity
references.citation: Proc Natl Acad Sci U S A. 1984 Aug;81(16):5126-9
references.pmid: 6591183
references.citation: Virol J. 2005 Feb 14;2:11
references.pmid: 15710048
references.citation: Biom J. 2008 Oct;50(5):861-9
references.pmid: 18932144
references.citation: Diabetes Care. 2009 Feb;32(2):245-50
references.pmid: 19001190
references.citation: Methods Inf Med. 2008;47(4):322-7
references.pmid: 18690365
references.citation: Comput Methods Programs Biomed. 2009 Jun;94(3):239-49
references.pmid: 19231022
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2009 Apr;79(4 Pt 1):040106
references.pmid: 19518161
references.citation: BMJ. 1999 Jul 24;319(7204):215-20
references.pmid: 10417082
references.citation: JAMA. 1992 Apr 1;267(13):1806-9
references.pmid: 1482430
references.citation: J Am Coll Cardiol. 1999 Jul;34(1):181-90
references.pmid: 10400009
references.citation: J Clin Neurophysiol. 2009 Aug;26(4):257-66
references.pmid: 19590434
references.citation: Int J Med Inform. 1997 Jun;45(1-2):65-74
references.pmid: 9291021
references.citation: Phys Med Biol. 2009 Apr 7;54(7):2015-27
references.pmid: 19287085
references.citation: J Neuroeng Rehabil. 2010 Jul 30;7:38
references.pmid: 20670457
references.citation: Diabetes. 1997 Apr;46(4):622-31
references.pmid: 9075802
references.citation: Nat Rev Neurosci. 2013 Jun;14(6):443-51
references.pmid: 23635871
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10101-6
references.pmid: 10963673
references.citation: Clin Chem. 2013 Jan;59(1):168-79
references.pmid: 23220226
references.citation: Lancet. 1996 May 11;347(9011):1312-4
references.pmid: 8622511
references.citation: Cancer Cell. 2014 Jan 13;25(1):91-101
references.pmid: 24434212
references.citation: PLoS One. 2010 Aug 18;5(8):e12262
references.pmid: 20805891
references.citation: J Gerontol. 1987 May;42(3):329-31
references.pmid: 3571870
references.citation: Neurobiol Aging. 2002 Jan-Feb;23(1):23-6
references.pmid: 11755014
references.citation: Genes Dev. 2008 Jul 1;22(13):1753-7
references.pmid: 18550784
references.citation: Diabetes. 2004 May;53(5):1181-6
references.pmid: 15111484
references.citation: PLoS Genet. 2007 Dec;3(12):e220
references.pmid: 18085826
references.citation: Biostatistics. 2002 Dec;3(4):445-57
references.pmid: 12933591
references.citation: Cancer Detect Prev. 2007;31(6):489-98
references.pmid: 18061365