- Bioinf-l - kam.mff.cuni.cz

Lecture invitation: A Telomere-to-Telomere (T2T) Mouse Genome Assembly
by Petr Danecek 18 Mar '24

18 Mar '24

Dear all, the next seminar will take place on Wednesday, please see the details below. We look forward to seeing you all! Title: A Telomere-to-Telomere (T2T) Mouse Genome Assembly Speaker: Bailey Francis (Wellcome Sanger Institute) Date and time: Wednesday 20/03/2024 - 17:20 Location: MFF UK, Malostranské nám. 25, lecture hall S4 https://bioinformatics.cuni.cz/seminar/ Best wishes, Petr Danecek ------------------------------- *Bailey Francis /A Telomere-to-Telomere (T2T) Mouse Genome Assembly: Towards the first complete mouse genome /* The generation and assembly of a reference genome for C57BL/6J revolutionized our ability to relate sequence to function, enabled genetic screens in mice to be performed on an unprecedented scale, and facilitated the task of creating a complete set of null alleles for all genes. Despite over twenty years of effort, the current mouse reference genome (GRCm39) has over 170 known gaps and unresolved issues. Many important loci such as the major histocompatibility complex (MHC) on chromosome 17, regions on chromosome X such as the pseudoautosomal region (PAR), and Krüppel-associated box (KRAB) domain-containing zinc-finger protein (KZFP) loci on chromosome 2 and 4, remain incomplete or inaccurate. By using a combination of novel high molecular weight DNA extraction methodologies and ultra-long sequencing technologies (PacBio HiFi and ultra-long Oxford Nanopore), we have generated the most complete mouse reference genome to date using mESCs from a C57BL/6J x CAST/EiJ F1 animal. We employed a trio-based genome assembly approach to achieve complete separation of haplotypes to produce two telomere-to-telomere (T2T) mouse reference genomes where the majority of chromosomes were assembled into a single contiguous sequence. This represents a major milestone in the journey towards a fully complete mouse reference genome. Key findings reveal that our C57BL/6J assembly fully closes over 91% of the autosomal gaps in GRCm39 with over 12 Mbp of novel sequence. Additionally, we have shown that our new T2T assemblies significantly improve the representation of previously hard-to-assemble regions when compared to the current reference genomes (e.g. PAR, inversions, KZFPs). Not only do our assemblies unlock some of the most challenging loci in the mouse genome, but with the near-completed genomic sequences for two mouse strains, our work enables comparative analyses in these complex regions for the very first time.

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Lecture invitation: Efficient Search of Microbial Genomes via Phylogenetic Compression
by Petr Danecek 17 Dec '23

17 Dec '23

Dear all, the next seminar will take place on Wednesday, please see the details below. We look forward to seeing you all! Title: Efficient Search of Microbial Genomes via Phylogenetic Compression Speaker: Karel Břinda (INRIA) Date and time: Wednesday 20/12/2023 - 17:20 Location: MFF UK, Malostranské nám. 25, lecture hall S3 (3rd floor) https://bioinformatics.cuni.cz/seminar/ Best wishes, Petr Danecek ------------------------------- *Karel Břinda (INRIA) /Efficient Search of Microbial Genomes via Phylogenetic Compression/* Comprehensive collections approaching millions of sequenced genomes have become central information sources in the life sciences. However, the rapid growth of these collections makes it effectively impossible to search these data using tools such as BLAST and its successors. In this talk, we will present a new technique called phylogenetic compression, which uses evolutionary history to guide compression and efficiently search large collections of microbial genomes using existing algorithms and data structures. We will show that, when applied to modern diverse collections approaching millions of genomes, lossless phylogenetic compression improves the compression ratios of assemblies, de Bruijn graphs, and k-mer indexes by one to two orders of magnitude. Additionally, we will present a pipeline for a BLAST-like search over these phylogeny-compressed reference data, and demonstrate it can align genes, plasmids, or entire sequencing experiments against all sequenced bacteria until 2019 on ordinary desktop computers within a few hours. Phylogenetic compression has broad applications in computational biology and may provide a fundamental design principle for future genomics infrastructure.

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Lecture invitation: dynamics of macromolecules and energetics of molecular interactions
by Petr Danecek 10 Dec '23

10 Dec '23

Dear all, the next seminar will take place on *Tuesday*, please see the details below. We look forward to seeing you all! Title: Probing the dynamics of macromolecules and energetics of molecular interactions with high-performance, fast and accessible computational methods Speaker: Rafael Najmanovich (University of Montreal) Date and time: *Tuesday 12/12/2023 - 10:40am* Location: *PřF UK, Viničná 7, room 311 (3rd floor)* https://bioinformatics.cuni.cz/seminar/ [bioinformatics.cuni.cz] Best wishes, Petr Danecek ------------------------------- *Probing the dynamics of macromolecules and energetics of molecular interactions with high-performance, fast and accessible computational methods* */Rafael Najmanovich (University of Montreal)/* In this talk I will discuss recent methods developed within our group for ultra-massive virtual screening, protein engineering and understanding macromolecular dynamics all based on basic simple biophysical principles leading to fas, accessible and high-performing computational methods with examples of their application in the study of GPCRs, SARS-CoV-2 and Ebola.

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Lecture invitation: Augusta
by Petr Danecek 21 Nov '23

21 Nov '23

Dear all, the next seminar will take place tomorrow, please see the details below. We look forward to seeing you all! Title: Augusta, a Python package for inferring Gene Regulatory and Boolean Networks using RNA-Seq and data mining Speaker: Jana Musilová (Brno University of Technology) Date and time: Wednesday 22/11/2023 - 17:20 Location: MFF UK, Malostranské nám. 25, lecture hall S3 https://bioinformatics.cuni.cz/seminar/ Best wishes, Petr Danecek ------------------------------- *Jana Musilová (Brno University of Technology)* */Augusta, a Python package for inferring Gene Regulatory and Boolean Networks using RNA-Seq and data mining/* Augusta is an open-source Python package for Gene Regulatory Network (GRN) and Boolean Network (BN) inference, based on a unique approach combining laboratory-generated data processing with the additional knowledge incorporation. In detail, the first estimation of a GRN is inferred by mutual information calculation from the high-throughput gene expression data. Subsequently, the GRN is refined by predicting transcription factor binding motifs within the promoters of regulated genes and integrating verified interactions obtained from curated databases. The refined GRN is finally transformed into a draft BN by searching in the curated model database CellCollective and adding logical rules to individual edges.

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Lecture invitation: Machine learning approaches for the identification of disease signatures
by Petr Danecek 08 May '23

08 May '23

Dear all, the next seminar will take place on Wednesday, please see the details below. We look forward to seeing you all! Title: Machine learning approaches for the identification of disease signatures Speaker: Carl Hermann (University of Heidelberg) Date and time: Wednesday 10/5/2023 - 17:20 Location: MFF UK, Malostranské nám. 25, lecture hall S4 https://bioinformatika.mff.cuni.cz/seminar Best wishes, Petr Danecek --------------------------------- *Carl Hermann (University of Heidelberg)** */*Machine learning approaches for the identification of disease signatures*/ In this presentation, I will review some recent work in which we have focused on extracting disease signatures from large-scale omics datasets using various linear and non-linear machine-learning approaches. In particular, I will present some recent work on building explainable AI models an their applications to various disease traits.

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Lecture invitation: MolMeDB
by Petr Danecek 18 Apr '23

18 Apr '23

Dear all, the next seminar will take place tomorrow, please see the details below. We look forward to seeing you all! Title: MolMeDB - databáze interakcí malých molekul s membránami a membránovými transportními proteiny Speaker: Kateřina Storchmannova (Palacký University Olomouc) Date and time: Wednesday19/4/2023 - 17:20 Location: MFF UK, Malostranské nám. 25, lecture hall S4 https://bioinformatika.mff.cuni.cz/seminar/ Best wishes, Petr Danecek ------------------------------- *Kateřina Storchmannova (Palacký University Olomouc) * /*MolMeDB - databáze interakcí malých molekul s membránami a membránovými transportními proteiny*/ Biologické membrány jsou přirozenými bariérami buněk a některých buněčných organel. Jako takové hrají důležitou roli ve farmakokinetice a farmakodynamice léčiv a dalších xenobiotik. K určení interakcí mezi molekulami a membránami se používá řada experimentálních i teoretických přístupů, ale neexistoval žádný otevřený zdroj těchto dat. Z tohoto důvodu jsme vytvořili databázi MolMeDB (Molecule on Membrane Database), která shromažďuje údaje o interakcích pro více než 500 000 molekul s membránami či membránovými transportními proteiny. Informace o interakcích byly shromážděny z vědeckých článků publikovaných v recenzovaných časopisech, z in-house výpočtů či z databází. MolMeDB může být mocným nástrojem, který může pomoci experimentátorům i teoretikům pomoci lépe pochopit chování látek na membránách.

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Lecture invitation: Masked superstrings as a unified framework for textual k-mer set representations
by Petr Danecek 27 Mar '23

27 Mar '23

Dear all, the next seminar will take place on Wednesday, please see the details below. We look forward to seeing you all! Title: Masked superstrings as a unified framework for textual k-mer set representations Speaker: Ondřej Sladký, Faculty of Mathematics and Physics, Charles University Date and time: Wednesday 27/3/2023 - 17:20 Location: MFF UK, Malostranské nám. 25, lecture hall S4 https://bioinformatika.mff.cuni.cz/seminar/ Best wishes, Petr Danecek ------------------------------- *Ondřej Sladký (Faculty of Mathematics and Physics, Charles University)* */Masked superstrings as a unified framework for textual k-mer set representations/* The popularity of k-mer-based methods has recently led to the development of compact k-mer-set representations, such as simplitigs/Spectrum-Preserving String Sets (SPSS), matchtigs, and eulertigs. These aim to represent k-mer sets via strings that contain individual k-mers as substrings more efficiently than the traditional unitigs. Here, we demonstrate that all such representations can be viewed as superstrings of input k-mers, and as such can be generalized into a unified framework that we call the masked superstring of k-mers. We study the complexity of masked superstring computation and prove NP-hardness for both k-mer superstrings and their masks. We then design local and global greedy heuristics for efficient computation of masked superstrings, implement them in a program called KmerCamel, and evaluate their performance using selected genomes and pan-genomes. Overall, masked superstrings unify the theory and practice of textual k-mer set representations and provide a useful framework for optimizing representations for specific bioinformatics applications.

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Lecture invitation: Disease maps: building and analysing graphical models of biomedical knowledge
by Petr Danecek 20 Mar '23

20 Mar '23

Dear all, the next seminar will take place on Wednesday, please see the details below. We look forward to seeing you all! Title: Disease maps: building and analysing graphical models of biomedical knowledge Speaker: Marek Ostaszewski, Luxembourg Centre for Systems Biomedicine Date and time: Wednesday 22/3/2023 - 17:20 Location: MFF UK, Malostranské nám. 25, lecture hall S3 https://bioinformatika.mff.cuni.cz/seminar/ Best wishes, Petr Danecek ------------------------------- *Marek Ostaszewski* */Disease maps: building and analysing graphical models of biomedical knowledge/* Disease maps encode knowledge about molecular pathophysiology in both visual and computational format, helping interdisciplinary exchange between bench scientists, clinical researchers and bioinformaticians. In this talk I’ll introduce the concept based on the example of Parkinson’s disease map and demonstrate it as a tool for visual exploration, analytics and investigating complex data. Then, I’ll describe the evolution of the approach and how it was picked up by a broader research community leading to a large-scale effort to build the COVID-19 Disease Map.

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Lecture invitation: Building complex bioinformatics pipelines using Snakemake
by Petr Danecek 06 Mar '23

06 Mar '23

Dear all, the next seminar will take place on Wednesday, please see the details below. We look forward to seeing you all! Title: Building complex bioinformatics pipelines using Snakemake Speaker: Joern Gerchen Date and time: Wednesday 8/3/2023 - 17:20 Location: MFF UK, Malostranské nám. 25, lecture hall S3 https://bioinformatika.mff.cuni.cz/seminar/ Best wishes, Petr Danecek ---------------- *Joern Gerchen: /Building complex bioinformatics pipelines using Snakemake/* Polyploidy, the presence of multiple genome copies as a result of whole-genome-duplications, is often thought to cause immediate repruductive isolation between polyploids and diploid relatives, due to inviability and sterility of hybrid offspring. However, recent research showed evidence of introgression (gene-flow via hybridization and backcrossing) between diploid and polyploid lineages. In this seminar I will introduce my PostDoc project, which uses population genomic analyses to quantify the degree of introgression between multiple natural plant lineages with variable ploidy and assess to what degree it can contribute to adaptive evolution. In order to determine the degree of inter-ploidy introgression, variant calling and subsequent population genomic analyses have to be run for each non-model species in a ploidy-aware manner. These analyses require complex custom bioinformatics pipelines, which have to be run repeatedly for multiple lineages on HPC computing clusters. Implementing and running these types of workflows in an efficient and reproducible manner can be challenging. As an approach to overcome these issues I will introduce Snakemake, which allows to implement automated, scalable and reproducible bioinformatics workflows.

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Lecture invitation: Functionalizing the cancer genome base-by-base with CRISPR editing and computational tools
by Petr Danecek 02 Dec '22

02 Dec '22

Dear all, the next seminar will take place next week, please see the details below. We look forward to seeing you all! Title: Functionalizing the cancer genome base-by-base with CRISPR editing and computational tools Speaker: Victoria Offord, WSI Date and time: Wednesday 7/12/2022 - 17:20 Location: MFF UK, Malostranské nám. 25, lecture hall S6 http://bioinformatics.cuni.cz/seminar Best wishes, Petr Danecek ------------------------------- Victoria Offord /Functionalizing the cancer genome base-by-base with CRISPR editing and computational tools/* * Over the last decade, the reduction in costs for high throughput technologies has enabled us to sequence more human genomes than ever before. We can see this in the rapid expansion of the repositories used to store and share genetic data amongst researchers. To date, over 1.5 million variants have been submitted to ClinVar, a public database of clinically relevant variants. However, over 50% of these are variants of uncertain significance (VUS) for which we have no clear interpretation of their function. Multiplexed Assays of Variant Effect (MAVEs) can be used to generate variant effect maps, which, over time, may be used to aid clinical interpretations. Saturation genome editing (SGE) is a CRISPR-based MAVE which allows us to test all possible single- and multi-nucleotide or amino acid variations across a genomic region. We’ll discuss SGE, the community, available resources, tools being developed and how the data that we’ve been generating may go on to aid in the interpretation of VUS.

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