Biomedical subjects

Valery Shepelev

Publications and source records attributed to Valery Shepelev.

4 recordsLinked to original sources

PubMed2026

A complete genome for the common marmoset.

The common marmoset is a New World monkey widely used to study primate evolution and human disease. We present a telomere-to-telomere (T2T) reference assembly for the species, plus three near-T2T haplotypes. These resolve previously inaccessible regions, including the centromeres, sex chromosomes, subterminal satellites, acrocentric chromosomes, and the major histocompatibility complex (MHC). We find marmoset centromeres carry dimeric alpha satellites with chromosomal specificity, flanked by inactive layers interpreted as ancestral centromere remnants. We assemble gene-poor, satellite-rich short arms of the acrocentrics and find that most can harbor rDNA and all share pseudo-homolog regions (PHRs). PHR-sharing chromosomes also share closely related centromeric satellites, consistent with a model of ongoing rDNA-facilitated recombinational exchange between heterologous chromosomes. We further identify over 500 marmoset-lineage-specific transcribed genes with previously unknown transcript models or expansions. These resources, along with a preliminary pangenome, improve the utility of the marmoset as a model organism and address gaps in primate genome evolution.

Animals↗

PubMed2006

Advances in the Exon-Intron Database (EID).

Investigation of exon-intron gene structures is a non-trivial task due to enormous expansions of the eukaryotic genomes, great variety of gene forms, and the imperfectness in sequence data. A number of available informational systems on various gene characteristics complement each other and are indispensable for many genomic studies. Among them, the Exon-Intron Database (EID) is a good choice for large-scale computational examination of exon/intron structure and splicing. It has many internal filters that control for sequence quality, consistency of gene descriptions, accordance to standards, and possible errors. New innovations in EID are described. The collection of exons and introns has been extended beyond coding regions and current versions of EID contain data on untranslated regions of gene sequences as well. Intron-less genes are included as a special part of EID. For species with entirely sequenced genomes, species-specific databases have been generated. A novel Mammalian Orthologous Intron Database (MOID) has been introduced which includes the full set of introns that come from orthologous genes that have the same positions relative to the reading frames. Examples of statistical analyses of gene sequences using EID are provided. We present the latest data on our comparison of intron positions in 11,025 orthologous genes of human, mouse and rat, and find no convincing cases of intron gain. We discuss relevant data-quality issues of genomic databases. In particular, 5% of genes in genomic databases contain internal stop codons. This fact is due to a combination of biological reasons and also to errors in sequence annotations. The EID is freely available at www.meduohio.edu/bioinfo/eid/.

Base Sequence↗

PubMed2005

Bioinformatic analysis of exon repetition, exon scrambling and trans-splicing in humans.

MOTIVATION: Using bioinformatic approaches we aimed to characterize poorly understood abnormalities in splicing known as exon scrambling, exon repetition and trans-splicing. RESULTS: We developed a software package that allows large-scale comparison of all human expressed sequence tags (EST) sequences to the entire set of human gene sequences. Among 5,992,495 EST sequences, 401 cases of exon repetition and 416 cases of exon scrambling were found. The vast majority of identified ESTs contain fragments rather than full-length repeated or scrambled exons. Their structures suggest that the scrambled or repeated exon fragments may have arisen in the process of cDNA cloning and not from splicing abnormalities. Nevertheless, we found 11 cases of full-length exon repetition showing that this phenomenon is real yet very rare. In searching for examples of trans-splicing, we looked only at reproducible events where at least two independent ESTs represent the same putative trans-splicing event. We found 15 ESTs representing five types of putative trans-splicing. However, all 15 cases were derived from human malignant tissues and could have resulted from genomic rearrangements. Our results provide support for a very rare but physiological occurrence of exon repetition, but suggest that apparent exon scrambling and trans-splicing result, respectively, from in vitro artifact and gene-level abnormalities. AVAILABILITY: Exon-Intron Database (EID) is available at http://www.meduohio.edu/bioinfo/eid. Programs are available at http://www.meduohio.edu/bioinfo/software.html. The Laboratory website is available at http://www.meduohio.edu/medicine/fedorov SUPPLEMENTARY INFORMATION: Supplementary file is available at http://www.meduohio.edu/bioinfo/software.html.

Algorithms↗

PubMed2005

Computer identification of snoRNA genes using a Mammalian Orthologous Intron Database.

Based on comparative genomics, we created a bioinformatic package for computer prediction of small nucleolar RNA (snoRNA) genes in mammalian introns. The core of our approach was the use of the Mammalian Orthologous Intron Database (MOID), which contains all known introns within the human, mouse and rat genomes. Introns from orthologous genes from these three species, that have the same position relative to the reading frame, are grouped in a special orthologous intron table. Our program SNO.pl searches for conserved snoRNA motifs within MOID and reports all cases when characteristic snoRNA-like structures are present in all three orthologous introns of human, mouse and rat sequences. Here we report an example of the SNO.pl usage for searching a particular pattern of conserved C/D-box snoRNA motifs (canonical C- and D-boxes and the 6 nt long terminal stem). In this computer analysis, we detected 57 triplets of snoRNA-like structures in three mammals. Among them were 15 triplets that represented known C/D-box snoRNA genes. Six triplets represented snoRNA genes that had only been partially characterized in the mouse genome. One case represented a novel snoRNA gene, and another three cases, putative snoRNAs. Our programs are publicly available and can be easily adapted and/or modified for searching any conserved motifs within mammalian introns.

Algorithms↗