Biology subjects

Gafurov, A.

Publications and source records attributed to Gafurov, A..

4 recordsLinked to original sources

bioRxiv2025

Noncanonical chromosomal-end-specific telomeric arrays in naturally telomerase-negative yeasts

In most eukaryotes, chromosomal DNA terminates with tandem repeats of a short G-rich motif, such as the canonical TTAGGG sequence. The arrays of telomeric repeats are maintained by telomerase or by alternative lengthening of telomeres (ALT). Here we report that nuclear chromosomes of several basidiomycetous yeasts classified into the order Microstromatales carry unusual telomeres. We demonstrate that instead of TTAGGG-like repeats these telomeres are composed of unique tandem arrays which are in most cases specific to a particular chromosomal end. In contrast to other basidiomycetes, the Microstromatales genomes lack orthologs coding for the telomerase catalytic subunit Est2 and a shelterin component Tpp1 indicating that noncanonical telomeric arrays are maintained by a telomerase-independent mechanism. We hypothesize that in a common ancestor of Microstromatales the loss of telomerase and Tpp1 was compensated by activation of an ALT mechanism, which promoted amplification of various motifs and formation of distinct telomeric arrays at most chromosomal ends.

molecular biology↗

bioRxiv2025

Identifying Positional Orthologs by Linear Programming

Studying the evolution of gene orders is essential to our understanding of the link between gene regulation and phenotype. Comparative studies concerning the full complement of genes in large numbers of genomes are now possible, thanks to the advent of affordable long-read sequencing and whole chromosome assembly, combined with automated genome annotation. The study of gene orders remains cumbersome, however, due to a lack of a streamlined, and standardized, process meant for the identification of positional orthologs. Within a family of homologous genes, these are those pairs of orthologous gene copies that descend from the same locus in their most recent ancestor, not having been produced by an intervening duplication event. This article approaches the detection of positional orthologs by way of the MAXIMUM COLORFUL GRAPH PARTITION Problem. We present two novel integer linear programming solutions to this problem, evaluate their efficacy on simulated and real data, while comparing them to several new and existing heuristics, as well as to the Double Cut and Join based ILP called FFGC. Digital Object Identifier10.4230/LIPIcs.CVIT.2016.23

bioinformatics↗

bioRxiv2023

Efficient Analysis of Annotation Colocalization Accounting for Genomic Contexts

An annotation is a set of genomic intervals sharing a particular function or property. Examples include genes or their exons, evolutionarily conserved elements, and regions with a particular epigenetic state. A common task is to compare two annotations to determine if one is enriched or depleted in the regions covered by the other. We study the problem of assigning statistical significance to such a comparison based on a null model representing two random unrelated annotations. To incorporate more background information into such analyses, we propose a new null model based on a Markov chain which differentiates among several genomic contexts. These contexts can capture various confounding factors, such as GC content or assembly gaps. We then develop a new algorithm for estimating p-values by computing the exact expectation and variance of the test statistics and then estimating the p-value using a normal approximation. Compared to the previous algorithm by Gafurov et al., the new algorithm provides three advances: (1) the running time is improved from quadratic to linear or quasi-linear, (2) the algorithm can handle two different test statistics, and (3) the algorithm can handle both simple and context-dependent Markov chain null models. We demonstrate the efficiency and accuracy of our algorithm on synthetic and real data sets, including the recent human telomere-to-telomere assembly. In particular, our algorithm computed p-values for 450 pairs of human genome annotations using 24 threads in under three hours. Moreover, the use of genomic contexts to correct for GC bias resulted in the reversal of some previously published findings. AvailabilityThe software is freely available at https://github.com/fmfi-compbio/mcdp2 under the MIT licence. All data for reproducibility are available at https://github.com/fmfi-compbio/mcdp2-reproducibility

bioinformatics↗

bioRxiv2022

Markov chains improve the significance computation of overlapping genome annotations

MotivationGenome annotations are a common way to represent genomic features such as genes, regulatory elements or epigenetic modifications. The amount of overlap between two annotations is often used to ascertain if there is an underlying biological connection between them. In order to distinguish between true biological association and overlap by pure chance, a robust measure of significance is required. One common way to do this is to determine if the number of intervals in the reference annotation that intersect the query annotation is statistically significant. However, currently employed statistical frameworks are often either inefficient or inaccurate when computing p-values on the scale of the whole human genome. ResultsWe show that finding the p-values under the typically used "gold" null hypothesis is[N][P] -hard. This motivates us to reformulate the null hypothesis using Markov chains. To be able to measure the fidelity of our Markovian null hypothesis, we develop a fast direct sampling algorithm to estimate the p-value under the gold null hypothesis. We then present an open-source software tool MCDP that computes the p-values under the Markovian null hypothesis in[O] (m2 + n) time and[O] (m) memory, where m and n are the numbers of intervals in the reference and query annotations, respectively. Notably, MCDP runtime and memory usage are independent from the genome length, allowing it to outperform previous approaches in runtime and memory usage by orders of magnitude on human genome annotations, while maintaining the same level of accuracy. AvailabilityThe software is available at https://github.com/fmfi-compbio/mc-overlaps. All data for reproducibility are available at https://github.com/fmfi-compbio/mc-overlaps-reproducibility

bioinformatics↗