Self-organizing maps for allele specific expression data reconstruction and identification of anomalous genomic regions

用于等位基因特异性表达数据重建和异常基因组区域识别的自组织映射

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Abstract

Allele Specific Expression data quantifies expression variation between the two haplotypes of a diploid individual distinguished by heterozygous sites. Current methodologies of genome-wide sequencing produce large amounts of missing data that may affect statistical inference and bias the outcome of experiments. Machine learning tools could be employed to explore the data and to estimate missing signatures. We present a two-phase procedure based on Self-Organizing Maps (SOMs), an unsupervised clustering technique, to recover missing allele specific expression data from RNA-seq experiments. Specifically, a SOM trained on a complete population P is used to assign a so-called corrupted individual p^ to its most fitting cluster c ; then, a completion rule based on allele frequencies within the subpopulation of Pc ⊆ P defined by c is employed to reconstruct p^ . To evaluate our approach, we first apply it to purely artificial datasets, in order to have full control over all experimental conditions. After that, we consider a real population of Vitis vinifera, which we also extend by applying a computational framework to generate synthetic individuals from allele expression data. We then introduce two local feature relevance indices in order to assess the influence of specific alleles on the topological placement of corrupted individuals in the SOM structure. Our results, showing promising accuracy in the prediction of missing alleles, suggest that the developed approach could be very useful for recovering incomplete samples in a dataset instead of discarding them, mainly in situations where experiments are challenging.

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