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We propose MT-MAG, a novel machine learning-based software tool for the complete or partial hierarchically-structured taxonomic classification of metagenome-assembled genomes (MAGs). MT-MAG is alignment-free, with k-mer frequencies being the only feature used to distinguish a DNA sequence from another (herein k = 7). MT-MAG is capable of classifying large and diverse metagenomic datasets: a total of 245.68 Gbp in the training sets, and 9.6 Gbp in the test sets analyzed in this study. In addition to complete classifications, MT-MAG offers a "partial classification" option, whereby a classification at a higher taxonomic level is provided for MAGs that cannot be classified to the Species level. MT-MAG outputs complete or partial classification paths, and interpretable numerical classification confidences of its classifications, at all taxonomic ranks. To assess the performance of MT-MAG, we define a "weighted classification accuracy," with a weighting scheme reflecting the fact that partial classifications at different ranks are not equally informative. For the two benchmarking datasets analyzed (genomes from human gut microbiome species, and bacterial and archaeal genomes assembled from cow rumen metagenomic sequences), MT-MAG achieves an average of 87.32% in weighted classification accuracy. At the Species level, MT-MAG outperforms DeepMicrobes, the only other comparable software tool, by an average of 34.79% in weighted classification accuracy. In addition, MT-MAG is able to completely classify an average of 67.70% of the sequences at the Species level, compared with DeepMicrobes which only classifies 47.45%. Moreover, MT-MAG provides additional information for sequences that it could not classify at the Species level, resulting in the partial or complete classification of 95.13%, of the genomes in the datasets analyzed. Lastly, unlike other taxonomic assignment tools (e.g., GDTB-Tk), MT-MAG is an alignment-free and genetic marker-free tool, able to provide additional bioinformatics analysis to confirm existing or tentative taxonomic assignments. [ABSTRACT FROM AUTHOR]

Motivation The mutations of cancers can encode the seeds of their own destruction, in the form of T-cell recognizable immunogenic peptides, also known as neoantigens. It is computationally challenging, however, to accurately prioritize the potential neoantigen candidates according to their ability of activating the T-cell immunoresponse, especially when the somatic mutations are abundant. Although a few neoantigen prioritization methods have been proposed to address this issue, advanced machine learning model that is specifically designed to tackle this problem is still lacking. Moreover, none of the existing methods considers the original DNA loci of the neoantigens in the perspective of 3D genome which may provide key information for inferring neoantigens' immunogenicity. Results In this study, we discovered that DNA loci of the immunopositive and immunonegative MHC-I neoantigens have distinct spatial distribution patterns across the genome. We therefore used the 3D genome information along with an ensemble pMHC-I coding strategy, and developed a group feature selection-based deep sparse neural network model (DNN-GFS) that is optimized for neoantigen prioritization. DNN-GFS demonstrated increased neoantigen prioritization power comparing to existing sequence-based approaches. We also developed a webserver named deepAntigen (http://yishi.sjtu.edu.cn/deepAntigen) that implements the DNN-GFS as well as other machine learning methods. We believe that this work provides a new perspective toward more accurate neoantigen prediction which eventually contribute to personalized cancer immunotherapy. Availability and implementation Data and implementation are available on webserver: http://yishi.sjtu.edu.cn/deepAntigen. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Abstract: Classic linear dimensionality reduction (LDR) methods, such as principal component analysis (PCA) and linear discriminant analysis (LDA), are known not to be robust against outliers. Following a systematic analysis of the multi-class LDR problem in a unified framework, we propose a new algorithm, called minimal distance maximization (MDM), to address the non-robustness issue. The principle behind MDM is to maximize the minimal between-class distance in the output space. MDM is formulated as a semi-definite program (SDP), and its dual problem reveals a close connection to “weighted” LDR methods. A soft version of MDM, in which LDA is subsumed as a special case, is also developed to deal with overlapping centroids. Finally, we drop the homoscedastic Gaussian assumption made in MDM by extending it in a non-parametric way, along with a gradient-based convex approximation algorithm to significantly reduce the complexity of the original SDP. The effectiveness of our proposed methods are validated on two UCI datasets and two face datasets. [ABSTRACT FROM AUTHOR]