Abstract:
:The cardiac muscle sarcomere contains multiple proteins contributing to contraction energy transduction and its regulation during a heartbeat. Inheritable heart disease mutants affect most of them but none more frequently than the ventricular myosin motor and cardiac myosin binding protein c (mybpc3). These co-localizing proteins have mybpc3 playing a regulatory role to the energy transducing motor. Residue substitution and functional domain assignment of each mutation in the protein sequence decides, under the direction of a sensible disease model, phenotype and pathogenicity. The unknown model mechanism is decided here using a method combing neural and Bayes networks. Missense single nucleotide polymorphisms (SNPs) are clues for the disease mechanism summarized in an extensive database collecting mutant sequence location and residue substitution as independent variables that imply the dependent disease phenotype and pathogenicity characteristics in 4 dimensional data points (4ddps). The SNP database contains entries with the majority having one or both dependent data entries unfulfilled. A neural network relating causes (mutant residue location and substitution) and effects (phenotype and pathogenicity) is trained, validated, and optimized using fulfilled 4ddps. It then predicts unfulfilled 4ddps providing the implicit disease model. A discrete Bayes network interprets fulfilled and predicted 4ddps with conditional probabilities for phenotype and pathogenicity given mutation location and residue substitution thus relating the neural network implicit model to explicit features of the motor and mybpc3 sequence and structural domains. Neural/Bayes network forecasting automates disease mechanism modeling by leveraging the world wide human missense SNP database that is in place and expanding.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Burghardt TP,Ajtai Kdoi
10.1016/j.yjmcc.2018.04.006subject
Has Abstractpub_date
2018-06-01 00:00:00pages
19-27eissn
0022-2828issn
1095-8584pii
S0022-2828(18)30101-9journal_volume
119pub_type
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journal_title:Journal of molecular and cellular cardiology
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更新日期:2017-07-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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doi:10.1016/0022-2828(83)90260-2
更新日期:1983-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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更新日期:2007-03-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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更新日期:2016-02-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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更新日期:1998-03-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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更新日期:1994-05-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.04.018
更新日期:2015-07-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
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更新日期:2008-11-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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更新日期:2015-08-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
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更新日期:2010-11-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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更新日期:2012-12-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.08.019
更新日期:2010-12-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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更新日期:1997-09-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(91)90974-q
更新日期:1991-06-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(91)90029-l
更新日期:1991-02-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2004.05.018
更新日期:2004-10-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.10.011
更新日期:2008-01-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80969-5
更新日期:1986-06-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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更新日期:1998-01-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(85)80087-0
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80905-1
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.02.010
更新日期:2015-05-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1078
更新日期:1994-05-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(95)90095-0
更新日期:1995-08-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(84)80040-1
更新日期:1984-12-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(84)80624-0
更新日期:1984-07-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(95)90425-5
更新日期:1995-08-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2012.05.010
更新日期:2012-09-01 00:00:00
abstract::Previous studies from our laboratory and others indicate that contraction-induced mechanical loading of cultured neonatal rat ventricular myocytes produces many of the phenotypic changes associated with cardiomyocyte hypertrophy in vivo, and that these changes occur via the activation of serine-threonine protein kinas...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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更新日期:2000-08-01 00:00:00