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Bioinform. Comput. Biol."],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:p> Modern biotechnologies have generated huge amount of OMIC data, among which transcriptomes and methylomes are two major OMIC types. Transcriptomes measure the expression levels of all the transcripts while methylomes depict the cytosine methylation levels across a genome. Both OMIC data types could be generated by array or sequencing. And some studies deliver many more features (the number of features is denoted as [Formula: see text]) for a sample than the number [Formula: see text] of samples in a cohort, which induce the \u201clarge [Formula: see text] small [Formula: see text]\u201d paradigm. This study focused on the classification problem about OMIC with \u201clarge [Formula: see text] small [Formula: see text]\u201d paradigm. A Siamese convolutional network was utilized to transform the OMIC features into a new space with minimized intra-class distances and maximized inter-class distances between the samples. The proposed feature engineering algorithm SiaCo was comprehensively evaluated using both transcriptome and methylome datasets. The experimental data showed that SiaCo generated SiaCo features with improved classification accuracies for binary classification problems, and achieved improvements on the independent test dataset. The individual SiaCo features did not show better inter-class discrimination powers than the original OMIC features. This may be due to that the Siamese convolutional network optimized the collective performances of the SiaCo features, instead of the individual feature\u2019s discrimination power. The inherent transformation nature of the Siamese twin network also makes the SiaCo features lack of interpretability. 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