Dear all,
our next seminar will take place on *Friday*, 17.1.2025, instead of our
usual Wednesday schedule, please see the details below. We look forward
to seeing you all!
Title: Beyond SWISS-MODEL - Modelling, Benchmarking and Working with
Computed Structure Models in the AlphaFold Era
Speaker: Gerardo Tauriello (SIB)
Date and time: Friday 17/1/2025 - 10am
Location: PřF UK, Viničná 7, lecture room B311
https://bioinformatics.cuni.cz/seminar/
Best wishes,
Petr Danecek
Dear all,
the next seminar will take place on Wednesday, please see the details
below. We look forward to seeing you all!
Title: Computational Analyses and Functional Annotations of Non-Model
Bacteria
Speaker: Karel Sedlář
Date and time: Wednesday 11/12/2024 - 17:20
Location: MFF UK, Malostranské nám. 25, lecture hall S3 (3rd floor)
https://bioinformatics.cuni.cz/seminar/
Best wishes,
Petr Danecek
-------------------------------
*Karel Sedlář*
*/Computational Analyses and Functional Annotations of Non-Model Bacteria/*
Bacteria are omnipresent organisms of unimaginable diversity. Non-model
ones hide tremendous biosynthetic potential for white biotechnology,
i.e., a technology that uses living cells to synthesize the value-added
chemicals. Bioinformatics analyses of non-model organisms are specific
because many computational tools require the use of datasets that are
unavailable for non-conventional bacteria due to non-existing
microbiological kits to perform desired experiments or simply due to
missing knowledge of required input data. This lecture brings the
author’s personal experience with overcoming these obstacles by using
unique combinations of computational tools and techniques in order to
maximize information gains from analyses of novel genomes of non-model
bacteria.
Dear all,
the next seminar will take place on Wednesday, please see the details
below. We look forward to seeing you all!
Title: Gene Off, Insights On: Mapping Molecular Phenotypes with MorPhiC
Speaker: Anu Shivalikanjli (EBI)
Date and time: Wednesday 27/11/2024 - 17:20
Location: MFF UK, Malostranské nám. 25, lecture hall S3 (3rd floor)
https://bioinformatics.cuni.cz/seminar/
Best wishes,
Petr Danecek
-------------------------------
*Anu Shivalikanjli*
*/Gene Off, Insights On: Mapping Molecular Phenotypes with MorPhiC
/
*We explore the molecular characteristics of cells that carry “null
alleles” in protein-coding genes, resulting in a diminished production
of their corresponding proteins. Using human induced pluripotent stem
cells (iPSCs), which may change into numerous cell types, we study how
these inactive genes affect cellular functions across the cell types.
With precise gene-editing techniques, we can selectively deactivate
genes and subsequently analyze the resulting changes using advanced
methodologies such as RNA sequencing, multi-omics, and imaging. These
approaches combined help us understand each gene's role and the
consequences of their inactivity. Our ultimate goal is to use these
models to map the effects of “null alleles” throughout the human genome.
Central to this effort is the MorPhiC project, a collaborative
initiative that unites multiple research centers to study “null alleles”
in lab-grown cell systems. MorPhiC focuses on generating, organizing,
and analyzing large datasets to catalog the molecular and cellular
effects of gene knockouts for all human genes. This initiative provides
a foothold understanding of how genes produce traits (phenotypes) as
well as the connections between genes and regulatory components in
biological pathways and networks, laying the way for future advances in
human genome research.
Dear all,
the next seminar will take place tomorrow, please see the details below.
We look forward to seeing you all!
Title: The genetic code and protein evolvability
Speaker: Hana Rozhoňová, M.Sc.
Date and time: Wednesday 6/11/2024 - 17:20
Location: MFF UK, Malostranské nám. 25, lecture hall S3 (3rd floor)
https://bioinformatics.cuni.cz/seminar/
Best wishes,
Petr Danecek
------------------------
*Hana Rozhoňová*
*/The genetic code and protein evolvability/*
The standard genetic code defines the rules of translation for nearly
every life form on Earth. It also determines the amino acid changes
accessible via single-nucleotide mutations, thus influencing protein
evolvability—the ability of mutation to bring forth adaptive variation
in protein function. One of the most striking features of the standard
genetic code is its robustness to mutation, yet it remains an open
question whether such robustness facilitates or frustrates protein
evolvability. To answer this question, we use data from massively
parallel sequence-to-function assays to construct and analyze 6
empirical adaptive landscapes under hundreds of thousands of rewired
genetic codes. We find that robust genetic codes tend to enhance protein
evolvability by rendering smooth adaptive landscapes with few peaks,
which are readily accessible from throughout sequence space. Whereas the
genetic codes that optimize evolvability depend to some extent on the
detailed relationship between amino acid sequence and protein function,
we also uncover general design principles for engineering nonstandard
genetic codes for enhanced and diminished evolvability, which may
facilitate directed protein evolution experiments and the
bio-containment of synthetic organisms, respectively.
Dear all,
the next seminar will take place on Wednesday *(tomorrow!)*, please see
the details below. We look forward to seeing you all!
Title: Semiempirical Quantum Mechanical Scoring in Structure-based
Drug Design
Speaker: Jan Řezáč (UOCHB AVCR)
Date and time: Wednesday 24.4.2024 - 17:20
Location: MFF UK, Malostranské nám. 25, lecture hall S4 (3rd floor)
https://bioinformatics.cuni.cz/seminar/
Best wishes,
Petr Danecek
Dear all,
the next seminar will take place on Wednesday, please see the details
below. We look forward to seeing you all!
Title: From human population variation to ligand binding sites via
SARS-CoV-2
Speaker: Geoff Barton (University of Dundee)
Date and time: Wednesday 17/04/2024 - 17:20
Location: MFF UK, Malostranské nám. 25, lecture hall S4
https://bioinformatics.cuni.cz/seminar/
Best wishes,
Petr Danecek
-------------------------------
*Geoff Barton (University of Dundee)*
*/From human population variation to ligand binding sites via SARS-CoV-2 /*
In this talk I will present an analysis that compares publicly available
variation data for human with variation seen across all available
protein sequences regardless of species. The analysis confirms patterns
of variation in human are consistent with protein structural features
(e.g. alpha-helix and begta-strand) but highlights structurally and
functionally important sites in around 15,000 human protein domains that
are not found by conventional sequence analysis methods. The identified
sites are enriched in disease-associated variants, ligand binding
residues and protein-protein interaction sites.
I will explain the method and illustrate the new analysis with examples
including the Nuclear Receptor Ligand Binding Domains and G-protein
coupled receptors (GPCRs) which are important therapeutic targets.
The study makes heavy use of the popular Jalview (www.jalview.org)
sequence analysis program developed since 1996 in my group, so I will
also give a brief update on Jalview’s new features for exploring nsSNPs
on alignments and three-dimensional structures including predictions by
AlphaFold.
Dear all,
the next seminar will take place on Wednesday, please see the details
below. We look forward to seeing you all!
Title: Computational methods for prosthetic vision: inferring
functional structure of the brain from its spontaneous activity
Speaker: Karolína Korvasová (Charles University, Faculty of Mathematics
and Physics)
Date and time: Wednesday 10/04/2024 - 17:20
Location: MFF UK, Malostranské nám. 25, lecture hall S4
https://bioinformatics.cuni.cz/seminar/
Best wishes,
Petr Danecek
-------------------------------
*
Karolína Korvasová* (Charles University, Faculty of Mathematics and Physics)
*/Computational methods for prosthetic vision: inferring functional
structure of the brain from its spontaneous activity/*
Being able to infer the functional structure of cortical neural networks
from their spontaneous activity would advance our understanding of
neural dynamics and have important applications in the field of visual
prosthetics, as functional properties of neurons in the visual cortex
cannot be measured directly in blind subjects. We designed a method that
estimates the structure of the orientation preference map in the primary
visual cortex. Using this method, we were able to show that functional,
as well as spatial properties of the sites stimulated with a cortical
visual prosthesis in blind humans determine the perceptual outcome. In
this talk I will first introduce some basic concepts of computational
neuroscience and discuss how biological neural networks can be modeled.
Next, I will briefly present a large-scale model of the primary visual
cortex developed in the group of Ján Antolík (MFF UK) that was used to
design the method that infers functional structure from spontaneous
activity. Finally, I will show the results of this method applied to
electrophysiological recordings from the visual cortex of sighted
non-human primates and blind human volunteers.
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.
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.
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.