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1.
IEEE/ACM Trans Comput Biol Bioinform ; 19(4): 2177-2187, 2022.
Article in English | MEDLINE | ID: mdl-33764878

ABSTRACT

Alternative splicing enables a gene translating into different isoforms and into the corresponding proteoforms, which actually accomplish various biological functions of a living body. Isoform-isoform interactions (IIIs) provide a higher resolution interactome to explore the cellular processes and disease mechanisms than the canonically studied protein-protein interactions (PPIs), which are often recorded at the coarse gene level. The knowledge of IIIs is critical to map pathways, understand protein complexity and functional diversity, but the known IIIs are very scanty. In this paper, we propose a deep learning based method called DeepIII to systematically predict genome-wide IIIs by integrating diverse data sources, including RNA-seq datasets of different human tissues, exon array data, domain-domain interactions (DDIs) of proteins, nucleotide sequences and amino acid sequences. Particularly, DeepIII fuses these data to learn the representation of isoform pairs with a four-layer deep neural networks, and then performs binary classification on the learnt representation to achieve the prediction of IIIs. Experimental results show that DeepIII achieves a superior prediction performance to the state-of-the-art solutions and the III network constructed by DeepIII gives more accurate isoform function prediction. Case studies further confirm that DeepIII can differentiate the individual interaction partners of different isoforms spliced from the same gene. The code and datasets of DeepIII are available at http://mlda.swu.edu.cn/codes.php?name=DeepIII.


Subject(s)
Alternative Splicing , Neural Networks, Computer , Alternative Splicing/genetics , Humans , Protein Isoforms/genetics
2.
Sci Rep ; 7(1): 9440, 2017 08 25.
Article in English | MEDLINE | ID: mdl-28842700

ABSTRACT

Metagenomics brings in new discoveries and insights into the uncultured microbial world. One fundamental task in metagenomics analysis is to determine the taxonomy of raw sequence fragments. Modern sequencing technologies produce relatively short fragments and greatly increase the number of fragments, and thus make the taxonomic classification considerably more difficult than before. Therefore, fast and accurate techniques are called to classify large-scale fragments. We propose EnSVM (Ensemble Support Vector Machine) and its advanced method called EnSVMB (EnSVM with BLAST) to accurately classify fragments. EnSVM divides fragments into a large confident (or small diffident) set, based on whether the fragments get consistent (or inconsistent) predictions from linear SVMs trained with different k-mers. Empirical study shows that sensitivity and specificity of EnSVM on confident set are higher than 90% and 97%, but on diffident set are lower than 60% and 75%. To further improve the performance on diffident set, EnSVMB takes advantage of best hits of BLAST to reclassify fragments in that set. Experimental results show EnSVM can efficiently and effectively divide fragments into confident and diffident sets, and EnSVMB achieves higher accuracy, sensitivity and more true positives than related state-of-the-art methods and holds comparable specificity with the best of them.


Subject(s)
Base Sequence/genetics , Metagenomics , Sequence Analysis, DNA/methods , Algorithms , Classification , Humans , Sensitivity and Specificity , Software , Support Vector Machine
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