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R, A.

Publications and source records attributed to R, A..

2 recordsLinked to original sources

Inference of splicing motifs through visualization of recurrent networks

Neural models have been able to obtain state-of-the-art performances on several genome sequence-based prediction tasks. Such models take only nucleotide sequences as input and learn relevant features on its own. However, extracting the interpretable motifs from the model remains a challenge. This work explores various existing visualization techniques in their ability to infer relevant sequence information learned by a recurrent neural network (RNN) on the task of splice junction identification. The visualization techniques have been modulated to suit the genome sequences as input. The visualizations inspect genomic regions at the level of a single nucleotide as well as a span of consecutive nucleotides. This inspection is performed based on modification of input sequences (perturbation-based) or the embedding space (back-propagation based). We infer features pertaining to both canonical and non-canonical splicing from a single neural model. Results indicate that the visualization techniques produce comparable performance for branchpoint detection. However, in case of canonical donor and acceptor junction motifs, perturbation based visualizations perform better than back-propagation based visualizations and vice-versa for non-canonical motifs.

bioinformatics

Rapid Therapeutic Recommendations in the Context of a Global Public Health Crisis using Translational Bioinformatics Approaches: A proof-of-concept study using Nipah Virus Infection

We live in a world of emerging new diseases and old diseases resurging in more aggressive forms. Drug development by pharmaceutical companies is a market-driven and costly endeavor, and thus it is often a challenge when drugs are needed for diseases endemic only to certain regions or which affect only a few patients. However, biomedical open data is accessible and reusable for reanalysis and generation of a new hypotheses and discovery. In this study, we leverage biomedical data and tools to analyze available data on Nipah Virus (NiV) infection. NiV infection is an emerging zoonosis that is transmissible to humans and is associated with high mortality rates. In this study, explored the application of computational drug repositioning and chemogenomic enrichment analyses using host transcriptome data to match drugs that could reverse the virus-induced gene signature. We performed analyses using two gene signatures: i) A previously published gene signature (n=34), and ii) a gene signature generated using the characteristic direction method (n= 5,533). Our predictive framework suggests that several drugs including FDA approved therapies like beclometasone, trihexyphenidyl, S-propranolol etc. could modulate the NiV infection induced gene signatures in endothelial cells. A target specific analysis of CXCL10 also suggests the potential application of Eldelumab, an investigative therapy for Crohns disease and ulcerative colitis, as a putative candidate for drug repositioning. To conclude, we also discuss challenges and opportunities in clinical trials (n-of-1 and adaptive trials) for repositioned drugs. Further follow-up studies including biochemical assays and clinical trials are required to identify effective therapies for clinical use. Our proof-of-concept study highlights that translational bioinformatics methods including gene expression analyses and computational drug repositioning could augment epidemiological investigations in the context of an emerging disease with no effective treatment.

microbiology