Monika Cechova
Biography
I am interested in the most complex parts of the human genome. I believe complete, Telomere-To-Telomere assemblies are the future of genomics that is happening now.
Interests
- Long reads and complete T2T genomes
- Y chromosome, centromeres, telomeres, acrocentric chromosomes
- Satellite Biology and Heterochromatin
- Aneuploidies
Education
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PhD Major in Biology, Minor in Statistics, 2020
Penn State, USA
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MS in Bioinformatics, 2013
Masaryk University, Brno
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BS in Applied Informatics, 2011
Masaryk University, Brno
Skills
R
Statistics
Python
Nanopore
6 years
PacBio
8 years
Illumina
12 years
Experience
Assistant Professor
Faculty of Informatics, Masaryk University, Brno
- Complex parts of human genomes: Y chromosome, acrocentric chromosomes, centromeres, telomeres
- Aneuploidies, machine learning for genomics
Postdoc
Department of Biomolecular Engineering, University of California, Santa Cruz
- T2T and HPRC consortia
- Gaining new understanding of the satellite DNA
Postdoc
Faculty of Informatics, Masaryk University
- Developing new algorithms, tools, and methods for bioinformatics
- Gaining new understanding of the repetitive DNA
Postdoc
Institute of Animal Physiology and Genetics CAS, v. v. i. Central European Institute of Technology; Department of Genetics and Reproduction, Veterinary Research Institute
- Early Embryonic Development
- Spindle Assembly Checkpoint
Graduate Student
Penn State
- Studied driving forces of Y chromosome evolution in great apes (Cechova, Vegesna et al. 2020)
- Explored evolution of heterochromatin in great apes (Cechova et al., 2019)
- Characterized genome-wide effects of non-B DNA on polymerization speed and error rate (Guiblet et al., 2018)
- Developed algorithms for the Y chromosome assembly (Rangavittal et al., 2018)
- Characterized genes, repeats and palindromes on gorilla Y chromosome (Tomaszkiewicz, Rangavittal, Cechova et al. 2016)
- Developed hybrid genome assembly algorithms for combining short and long reads (Tomaszkiewicz, Rangavittal, Cechova et al. 2016)
Bioinformatician
Institute of Biophysics, Academy of Sciences of the Czech Republic
- Developed pipelines for detection of sex-linked genes from NGS data (Cechova et al., 2015)
- Characterized nupts and numts in 6 plant species, their age, length, distribution, consequences of insertions, etc. (Cechova et al., 2013)
- Explored microsatellites-TEs association and microsatellite periodicity (Kejnovsky et al., 2013)
Awards
The program of support for promising postdoctoral students (PPLZ)
Mohnkern scholarship
Hill-Hill Memorial Fund Fellowship
Troxell Memorial Scholarship in Biology
CBIOS (NIH T32 Predoctoral Training Grant)
Braddock Scholarship
Best Poster Award, Genetics Conference, Lednice
Featured Publications
The complete sequence of a human Y chromosome
The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure that includes long palindromes, tandem repeats and segmental duplications1,2,3. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished4,5. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, showing the complete ampliconic structures of gene families TSPY, DAZ and RBMY; 41 additional protein-coding genes, mostly from the TSPY family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region. We have combined T2T-Y with a previous assembly of the CHM13 genome4 and mapped available population variation, clinical variants and functional genomics data to produce a complete and comprehensive reference sequence for all 24 human chromosomes.
Dynamic evolution of great ape Y chromosomes
The male-specific Y chromosome harbors genes important for sperm production. Because Y is repetitive, its DNA sequence was deciphered for only a few species, and its evolution remains elusive. Here we compared the Y chromosomes of great apes (human, chimpanzee, bonobo, gorilla, and orangutan) and found that many of their repetitive sequences and multicopy genes were likely already present in their common ancestor. Y repeats had increased intrachromosomal contacts, which might facilitate preservation of genes and gene regulatory elements. Chimpanzee and bonobo, experiencing high sperm competition, underwent many DNA changes and gene losses on the Y. Our research is significant for understanding the role of the Y chromosome in reproduction of nonhuman great apes, all of which are endangered.
Recent Publications
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The complete sequence and comparative analysis of ape sex chromosomes
Apes possess two sex chromosomes—the male-specific Y chromosome and the X chromosome, which is present in both males and females. The Y chromosome is crucial for male reproduction, with deletions being linked to infertility1. The X chromosome is vital for reproduction and cognition2. Variation in mating patterns and brain function among apes suggests corresponding differences in their sex chromosomes. However, owing to their repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the methodology developed for the telomere-to-telomere (T2T) human genome, we produced gapless assemblies of the X and Y chromosomes for five great apes (bonobo (Pan paniscus), chimpanzee (Pan troglodytes), western lowland gorilla (Gorilla gorilla gorilla), Bornean orangutan (Pongo pygmaeus) and Sumatran orangutan (Pongo abelii)) and a lesser ape (the siamang gibbon (Symphalangus syndactylus)), and untangled the intricacies of their evolution. Compared with the X chromosomes, the ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements—owing to the accumulation of lineage-specific ampliconic regions, palindromes, transposable elements and satellites. Many Y chromosome genes expand in multi-copy families and some evolve under purifying selection. Thus, the Y chromosome exhibits dynamic evolution, whereas the X chromosome is more stable. Mapping short-read sequencing data to these assemblies revealed diversity and selection patterns on sex chromosomes of more than 100 individual great apes. These reference assemblies are expected to inform human evolution and conservation genetics of non-human apes, all of which are endangered species.
Accurate sequencing of DNA motifs able to form alternative (non-B) structures
Approximately 13% of the human genome at certain motifs have the potential to form noncanonical (non-B) DNA structures (e.g., G-quadruplexes, cruciforms, and Z-DNA), which regulate many cellular processes but also affect the activity of polymerases and helicases. Because sequencing technologies use these enzymes, they might possess increased errors at non-B structures. To evaluate this, we analyzed error rates, read depth, and base quality of Illumina, Pacific Biosciences (PacBio) HiFi, and Oxford Nanopore Technologies (ONT) sequencing at non-B motifs. All technologies showed altered sequencing success for most non-B motif types, although this could be owing to several factors, including structure formation, biased GC content, and the presence of homopolymers. Single-nucleotide mismatch errors had low biases in HiFi and ONT for all non-B motif types but were increased for G-quadruplexes and Z-DNA in all three technologies. Deletion errors were increased for all non-B types but Z-DNA in Illumina and HiFi, as well as only for G-quadruplexes in ONT. Insertion errors for non-B motifs were highly, moderately, and slightly elevated in Illumina, HiFi, and ONT, respectively. Additionally, we developed a probabilistic approach to determine the number of false positives at non-B motifs depending on sample size and variant frequency, and applied it to publicly available data sets (1000 Genomes, Simons Genome Diversity Project, and gnomAD). We conclude that elevated sequencing errors at non-B DNA motifs should be considered in low-read-depth studies (single-cell, ancient DNA, and pooled-sample population sequencing) and in scoring rare variants. Combining technologies should maximize sequencing accuracy in future studies of non-B DNA.
HiC TE, a computational pipeline for HiC data analysis to study the role of repeat family interactions in the genome 3D organization
The role of repetitive DNA in the 3D organization of the interphase nucleus is a subject of intensive study. In studies of 3D nucleus organization, mutual contacts of various loci can be identified by HiC sequencing. Typical analyses use binning of read pairs by location to reduce noise. We use binning by repeat families instead to make similar conclusions about repeat regions. To achieve this, we combined HiC data, reference genome data and tools for repeat analysis into a Nextflow pipeline identifying and quantifying the contacts of specific repeat families. As an output, our pipeline produces heatmaps showing contact frequency and circular diagrams visualizing repeat contact localization. Using our pipeline with tomato data, we revealed the preferential homotypic interactions of ribosomal DNA, centromeric satellites and some LTR retrotransposon families and, as expected, little contact between organellar and nuclear DNA elements. While the pipeline can be applied to any eukaryotic genome, results in plants provide better coverage, since the built in TE greedy nester software only detects tandems and LTR retrotransposons. Other repeats can be fed via GFF3 files. This pipeline represents a novel and reproducible way to analyze the role of repetitive elements in the 3D organization of genomes.
The complete sequence of a human Y chromosome
The human Y chromosome has been notoriously difficult to sequence and assemble because of its complex repeat structure that includes long palindromes, tandem repeats and segmental duplications1,2,3. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished4,5. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, showing the complete ampliconic structures of gene families TSPY, DAZ and RBMY; 41 additional protein-coding genes, mostly from the TSPY family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region. We have combined T2T-Y with a previous assembly of the CHM13 genome4 and mapped available population variation, clinical variants and functional genomics data to produce a complete and comprehensive reference sequence for all 24 human chromosomes.
Satellite DNAs and human sex chromosome variation
Satellite DNAs are present on every chromosome in the cell and are typically enriched in repetitive, heterochromatic parts of the human genome. Sex chromosomes represent a unique genomic and epigenetic context. In this review, we first report what is known about satellite DNA biology on human X and Y chromosomes, including repeat content and organization, as well as satellite variation in typical euploid individuals. Then, we review sex chromosome aneuploidies that are among the most common types of aneuploidies in the general population, and are better tolerated than autosomal aneuploidies. This is demonstrated also by the fact that aging is associated with the loss of the X, and especially the Y chromosome. In addition, supernumerary sex chromosomes enable us to study general processes in a cell, such as analyzing heterochromatin dosage (i.e. additional Barr bodies and long heterochromatin arrays on Yq) and their downstream consequences. Finally, genomic and epigenetic organization and regulation of satellite DNA could influence chromosome stability and lead to aneuploidy. In this review, we argue that the complete annotation of satellite DNA on sex chromosomes in human, and especially in centromeric regions, will aid in explaining the prevalence and the consequences of sex chromosome aneuploidies.
Contact
- cechova.biomonika@gmail.com
- Brno, Czechia 61500
- DM Me