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Yankilevich, P.

Publications and source records attributed to Yankilevich, P..

2 recordsLinked to original sources

Gene function prediction in five model eukaryotes based on gene relative location through machine learning

MotiviationThe function of most genes is unknown. The best results in gene function prediction are obtained with machine learning-based methods that combine multiple data sources, typically sequence derived features, protein structure and interaction data. Even though there is ample evidence showing that a genes function is not independent of its location, the few available examples of gene function prediction based on gene location relay on sequence identity between genes of different organisms and are thus subjected to the limitations of the relationship between sequence and function. ResultsHere we predict thousands of gene functions in five eukaryotes (Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens) using machine learning models trained with features derived from the location of genes in the genomes to which they belong. To the best of our knowledge this is the first work in which gene function prediction is successfully achieved in eukaryotic genomes using predictive features derived exclusively from the relative location of the genes. Contactfpazos@iibce.edu.uy Supplementary informationhttp://gfpml.bnd.edu.uy

bioinformatics↗

miRNome profiling of clonal stem cells in Ph+ CML

Chronic myeloid leukemia (CML) is a myeloid stem cell neoplasm characterized by an expansion of myeloid progenitor cells and the presence of BCR-ABL1 oncoprotein. Since the introduction of specific BCR-ABL1 tyrosine kinase inhibitors (TKI), overall survival has improved significantly. However, under long-term therapy patients may have residual disease that originates from TKI-resistant leukemic stem cells (LSC). In this work, we analyzed the miRNome of CML LSC, normal hematopoietic stem cells (HSC) obtained from the same CML patients, and stem and progenitor cells obtained from healthy donors (HD) by next-generation sequencing. We detected a global decrease of microRNA levels in LSC and HSC from CML patients, and decreased levels of microRNAs and snoRNAs from a genomic cluster in chromosome 14, suggesting a mechanism of silencing of multiple non-coding RNAs. Surprisingly, HSC from CML patients, despite the absence of BCR-ABL1 expression, showed an altered miRNome. In silico analysis revealed an association between validated microRNAs and multiple metabolic pathways, suggesting that these molecules may be mediators of the previously reported dysregulation of LSC metabolism. This is the first report of the LSC miRNome that distinguishes between BCR-ABL1+ LSC and their BCR-ABL1- counterparts, providing valuable data for future studies.

cancer biology↗