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Function annotation of peptides generated from the non-coding regions of D. melanogaster genome.

ABSTRACT: De novo emergence of genes is the most fundamental form of genetic diversity that is attracting the attention of the scientific community. Identification of short open reading frames (sORFs) from the non-coding regions of different genomes has been leading this thought recently. The coding potential of these newly identified sORFs have been investigated through experimental and computational approaches in recent studies. In the present work we have tried to make peptides from intergenic sequences of D. melanogaster genome leading to therapeutic applications. Towards this goal of making novel peptides from non-coding genome, we have found strong computational evidence of 145 peptides with conformational stability from the intergenic sequences of D. melanogaster. The structure of these completely unique peptides was predicted using ab initio method. The function annotation of these peptides was carried out using this structural information. The newly generated proteins were categorised as DNA/Protein/ion binding proteins, electron transporters and a very few as enzymes too. Experimental studies can certainly provide validations to these preliminary findings. This work provides further evidence of untapped potential of non-coding genome.

SUBMITTER: Deepthi V

PROVIDER: S-EPMC5267965 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Function annotation of peptides generated from the non-coding regions of D. melanogaster genome.

Deepthi Varughese V V I Nair Vineetha V Thomas Vipin V Raj Navya N P Ramakrishnan Shidhi S Khan Juveria J Kaushik Monika M K Dhar Pawan P S Nair Achuthsankar A

Bioinformation 20160615 3

De novo emergence of genes is the most fundamental form of genetic diversity that is attracting the attention of the scientific community. Identification of short open reading frames (sORFs) from the non-coding regions of different genomes has been leading this thought recently. The coding potential of these newly identified sORFs have been investigated through experimental and computational approaches in recent studies. In the present work we have tried to make peptides from intergenic sequence ...[more]

PMID: 28149056

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Project description:Multiple sclerosis (MS) is the most common neurological disorder in young adults. Despite extensive studies, only a fraction of MS heritability has been explained, with association studies focusing primarily on protein-coding genes, essentially for the difficulty of interpreting non-coding features. However, non-coding RNAs (ncRNAs) and functional elements, such as super-enhancers (SE), are crucial regulators of many pathways and cellular mechanisms, and they have been implicated in a growing number of diseases. In this work, we searched for possible enrichments in non-coding elements at MS genome-wide associated loci, with the aim to highlight their possible involvement in the susceptibility to the disease. We first reconstructed the linkage disequilibrium (LD) structure of the Italian population using data of 727,478 single-nucleotide polymorphisms (SNPs) from 1,668 healthy individuals. The genomic coordinates of the obtained LD blocks were intersected with those of the top hits identified in previously published MS genome-wide association studies (GWAS). By a bootstrapping approach, we hence demonstrated a striking enrichment of non-coding elements, especially of circular RNAs (circRNAs) mapping in the 73 LD blocks harboring MS-associated SNPs. In particular, we found a total of 482 circRNAs (annotated in publicly available databases) vs. a mean of 194 ± 65 in the random sets of LD blocks, using 1,000 iterations. As a proof of concept of a possible functional relevance of this observation, we experimentally verified that the expression levels of a circRNA derived from an MS-associated locus, i.e., hsa_circ_0043813 from the STAT3 gene, can be modulated by the three genotypes at the disease-associated SNP. Finally, by evaluating RNA-seq data of two cell lines, SH-SY5Y and Jurkat cells, representing tissues relevant for MS, we identified 18 (two novel) circRNAs derived from MS-associated genes. In conclusion, this work showed for the first time that MS-GWAS top hits map in LD blocks enriched in circRNAs, suggesting circRNAs as possible novel contributors to the disease pathogenesis.

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Function annotation of peptides generated from the non-coding regions of D. melanogaster genome.

Publications

Function annotation of peptides generated from the non-coding regions of D. melanogaster genome.

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