Biology subjects

Dvorkina, T.

Publications and source records attributed to Dvorkina, T..

5 recordsLinked to original sources

bioRxiv2021

HORmon: automated annotation of human centromeres

Recent advances in long-read sequencing opened a possibility to address the long-standing questions about the architecture and evolution of human centromeres. They also emphasized the need for centromere annotation (partitioning human centromeres into monomers and higher-order repeats (HORs)). Even though there was a half-century-long series of semi-manual studies of centromere architecture, a rigorous centromere annotation algorithm is still lacking. Moreover, an automated centromere annotation is a prerequisite for studies of genetic diseases associated with centromeres, and evolutionary studies of centromeres across multiple species. Although the monomer decomposition (transforming a centromere into a monocentromere written in the monomer alphabet) and the HOR decomposition (representing a monocentromere in the alphabet of HORs) are currently viewed as two separate problems, we demonstrate that they should be integrated into a single framework in such a way that HOR (monomer) inference affects monomer (HOR) inference. We thus developed the HORmon algorithm that integrates the monomer/HOR inference and automatically generates the human monomers/HORs that are largely consistent with the previous semi-manual inference.

bioinformatics↗

bioRxiv2021

Complete genomic and epigenetic maps of human centromeres

Existing human genome assemblies have almost entirely excluded highly repetitive sequences within and near centromeres, limiting our understanding of their sequence, evolution, and essential role in chromosome segregation. Here, we present an extensive study of newly assembled peri/centromeric sequences representing 6.2% (189.9 Mb) of the first complete, telomere-to-telomere human genome assembly (T2T-CHM13). We discovered novel patterns of peri/centromeric repeat organization, variation, and evolution at both large and small length scales. We also found that inner kinetochore proteins tend to overlap the most recently duplicated subregions within centromeres. Finally, we compared chromosome X centromeres across a diverse panel of individuals and uncovered structural, epigenetic, and sequence variation at single-base resolution across these regions. In total, this work provides an unprecedented atlas of human centromeres to guide future studies of their complex and critical functions as well as their unique evolutionary dynamics. One-sentence summaryDeep characterization of fully assembled human centromeres reveals their architecture and fine-scale organization, variation, and evolution.

genomics↗

bioRxiv2021

The complete sequence of a human genome

In 2001, Celera Genomics and the International Human Genome Sequencing Consortium published their initial drafts of the human genome, which revolutionized the field of genomics. While these drafts and the updates that followed effectively covered the euchromatic fraction of the genome, the heterochromatin and many other complex regions were left unfinished or erroneous. Addressing this remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium has finished the first truly complete 3.055 billion base pair (bp) sequence of a human genome, representing the largest improvement to the human reference genome since its initial release. The new T2T-CHM13 reference includes gapless assemblies for all 22 autosomes plus Chromosome X, corrects numerous errors, and introduces nearly 200 million bp of novel sequence containing 2,226 paralogous gene copies, 115 of which are predicted to be protein coding. The newly completed regions include all centromeric satellite arrays and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies for the first time.

genomics↗

bioRxiv2019

The String Decomposition Problem and its Applications to Centromere Assembly

Recent attempts to assemble long tandem repeats (such as multi-megabase long centromeres) faced the challenge of accurate translation of long error-prone reads from the nucleotide alphabet into the alphabet of repeat units. Centromeres represent a particularly complex type of nested tandem repeats, where each unit is itself a repeat formed by chromosome-specific monomers (a repeat within repeat). Given a set of monomers forming a specific centromere, translation of a read into monomers is modeled as the String Decomposition Problem, finding a concatenate of monomers with the highest-scoring sequence alignment to a given read. We developed a StringDecomposer algorithm for solving this problem, benchmarked it on the set of reads generated by the Telomere-to-Telomere consortium, and identified a novel (rare) monomer that extends the set of twelve X-chromosome specific monomers identified more than three decades ago. The accurate translation of each read into a monomer alphabet turns centromere assembly into a more tractable problem than the notoriously difficult problem of assembling centromeres in the nucleotide alphabet. Our identification of a novel monomer emphasizes the importance of careful identification of all (even rare) monomers for follow-up centromere assembly efforts.

bioinformatics↗

bioRxiv2019

SPAligner: alignment of long diverged molecular sequences to assembly graphs

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSGraph-based representation of genome assemblies has been recently used in different applications -- from gene finding to haplotype separation. While most of these applications are based on the alignment of molecular sequences to assembly graphs, existing software tools for finding such alignments have important limitations.\n\nResultsWe present a novel SPAligner tool for aligning long diverged molecular sequences to assembly graphs and demonstrate that SPAligner is an efficient solution for mapping third generation sequencing data and can also facilitate the identification of known genes in complex metagenomic datasets.\n\nConclusionsOur work will facilitate accelerating the development of graph-based approaches in solving sequence to genome assembly alignment problem. SPAligner is implemented as a part of SPAdes tools library and is available on https://github.com/ablab/spades/archive/spaligner-paper.zip.

bioinformatics↗