Discovering Typical Transcription-Factors Patterns in Gene Expression Levels of Mouse Embryonic Stem Cells by Instance-Based Classifiers

The development of high-throughput technology in genome sequencing provide a large amount of raw data to study the regulatory functions of transcription factors (TFs) on gene expression. It is possible to realize a classifier system in which the gene expression level, under a certain condition, is regarded as the response variable and features related to TFs are taken as predictive variables. In this paper we consider the families of Instance-Based (IB) classifiers, and in particular the Prototype exemplar learning classifier (PEL-C), because IB-classifiers can infer a mixture of representative instances, which can be used to discover the typical epigenetic patterns of transcription factors which explain the gene expression levels. We consider, as case study, the gene regulatory system in mouse embryonic stem cells (ESCs). Experimental results show IB-classifier systems can be effectively used for quantitative modelling of gene expression levels because more than 50% of variation in gene expression can be explained using binding signals of 12 TFs; moreover the PEL-C identifies nine typical patterns of transcription factors activation that provide new insights to understand the gene expression machinery of mouse ESCs.

[1]  Roberto Pirrone,et al.  AI*IA 2011: Artificial Intelligence Around Man and Beyond - XIIth International Conference of the Italian Association for Artificial Intelligence, Palermo, Italy, September 15-17, 2011. Proceedings , 2011, AI*IA.

[2]  Francesco Gagliardi,et al.  Instance-based classifiers applied to medical databases: Diagnosis and knowledge extraction , 2011, Artif. Intell. Medicine.

[3]  W. Wong,et al.  ChIP-Seq of transcription factors predicts absolute and differential gene expression in embryonic stem cells , 2009, Proceedings of the National Academy of Sciences.

[4]  Ian H. Witten,et al.  Data mining: practical machine learning tools and techniques, 3rd Edition , 1999 .

[5]  Trevor Hastie,et al.  The Elements of Statistical Learning , 2001 .

[6]  Ian Witten,et al.  Data Mining , 2000 .

[7]  Trevor Hastie,et al.  Prototype Methods and Nearest-Neighbors , 2009 .

[8]  Michael P Snyder,et al.  High-throughput sequencing for biology and medicine , 2013, Molecular systems biology.

[9]  Ian H. Witten,et al.  Data mining: practical machine learning tools and techniques with Java implementations , 2002, SGMD.

[10]  G. Hon,et al.  Next-generation genomics: an integrative approach , 2010, Nature Reviews Genetics.

[11]  J. Franklin,et al.  The elements of statistical learning: data mining, inference and prediction , 2005 .

[12]  Matthew D. Young,et al.  ChIP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity , 2011, Nucleic acids research.

[13]  William Stafford Noble,et al.  Matrix2png: a utility for visualizing matrix data , 2003, Bioinform..

[14]  Gregory Piatetsky-Shapiro,et al.  Advances in Knowledge Discovery and Data Mining , 2004, Lecture Notes in Computer Science.

[15]  Francesco Gagliardi Instance-Based Classifiers to Discover the Gradient of Typicality in Data , 2011, AI*IA.

[16]  Giacomo Patrizi,et al.  Formal methods in pattern recognition: A review , 2000, Eur. J. Oper. Res..