21,612 research outputs found

    A novel framework to elucidate core classes in a dataset

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    In this paper we present an original framework to extract representative groups from a dataset, and we validate it over a novel case study. The framework specifies the application of different clustering algorithms, then several statistical and visualisation techniques are used to characterise the results, and core classes are defined by consensus clustering. Classes may be verified using supervised classification algorithms to obtain a set of rules which may be useful for new data points in the future. This framework is validated over a novel set of histone markers for breast cancer patients. From a technical perspective, the resultant classes are well separated and characterised by low, medium and high levels of biological markers. Clinically, the groups appear to distinguish patients with poor overall survival from those with low grading score and better survival. Overall, this framework offers a promising methodology for elucidating core consensus groups from data

    Machine learning and structural analysis of Mycobacterium tuberculosis pan-genome identifies genetic signatures of antibiotic resistance.

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    Mycobacterium tuberculosis is a serious human pathogen threat exhibiting complex evolution of antimicrobial resistance (AMR). Accordingly, the many publicly available datasets describing its AMR characteristics demand disparate data-type analyses. Here, we develop a reference strain-agnostic computational platform that uses machine learning approaches, complemented by both genetic interaction analysis and 3D structural mutation-mapping, to identify signatures of AMR evolution to 13 antibiotics. This platform is applied to 1595 sequenced strains to yield four key results. First, a pan-genome analysis shows that M. tuberculosis is highly conserved with sequenced variation concentrated in PE/PPE/PGRS genes. Second, the platform corroborates 33 genes known to confer resistance and identifies 24 new genetic signatures of AMR. Third, 97 epistatic interactions across 10 resistance classes are revealed. Fourth, detailed structural analysis of these genes yields mechanistic bases for their selection. The platform can be used to study other human pathogens
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