A5064553103- Genomics and Phylogenetic Studies
- Gene expression and cancer classification
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Advanced Graph Theory Research
- Genetic diversity and population structure
- Complexity and Algorithms in Graphs
- Bioinformatics and Genomic Networks
- Genome Rearrangement Algorithms
- Chromosomal and Genetic Variations
- Algorithms and Data Compression
- Bayesian Modeling and Causal Inference
- Genetics, Bioinformatics, and Biomedical Research
- Evolution and Paleontology Studies
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- RNA modifications and cancer
- T-cell and B-cell Immunology
- Limits and Structures in Graph Theory
- Computational Geometry and Mesh Generation
- Biomedical Text Mining and Ontologies
- RNA regulation and disease
- Molecular Biology Techniques and Applications
- Graph Labeling and Dimension Problems
KTH Royal Institute of Technology
2015-2025
Science for Life Laboratory
2015-2025
Swedish e-Science Research Centre
2004-2018
Karolinska Institutet
2012-2018
Karolinska University Hospital
2015
Université Claude Bernard Lyon 1
2014
Centre National de la Recherche Scientifique
2014
Stockholm University
2008-2014
Laboratoire de Biométrie et Biologie Evolutive
2014
AlbaNova
2006-2009
Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression throughout a multifocal prostate using spatial transcriptomics (ST) technology. Utilizing novel approach for deconvolution, analyze transcriptomes nearly 6750 tissue regions and extract distinct profiles different components, such as stroma, normal PIN glands, immune cells cancer. We distinguish healthy diseased areas thereby provide insight into changes...
The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed transcriptomics variable, diversity, joining (VDJ) sequences (Spatial VDJ), a method that maps B cell T receptor in human tissue sections. Spatial VDJ captures match canonical distributions amplifies clonal confirmed by orthogonal methods. found congruency between paired chains, computational framework predict pairs, linked the expansion distinct...
Cell types can be classified according to shared patterns of transcription. Non-genetic variability among individual cells the same type has been ascribed stochastic transcriptional bursting and transient cell states. Using high-coverage single-cell RNA profiling, we asked whether long-term, heritable differences in gene expression impart diversity within type. Studying clonal human lymphocytes mouse brain cells, uncovered a vast different clones vivo. We combined chromatin accessibility...
Attachment of SUMO lets insulin-like growth factor receptors act as transcriptional regulators in the nucleus.
The incongruency between a gene tree and corresponding species can be attributed to evolutionary events such as duplication loss. This paper describes combinatorial model where so-called DTL-scenarios are used explain the differences taking into account duplications, losses, lateral transfers (also known horizontal transfers). reasonable biological constraint that transfer may only occur contemporary leads notion of acyclic DTL-scenarios. Parsimony methods introduced by defining appropriate...
We present GSR, a probabilistic model integrating gene duplication, sequence evolution, and relaxed molecular clock for substitution rates, that enables genomewide analysis of families. The duplication loss process is major cause incongruence between species tree, deterministic methods have been developed to explain such differences through tree reconciliations. Although phylogenetic inference around decades, reconciliation are far less established. Based on our model, we implemented...
Metastatic breast cancers are still incurable. Characterizing the evolutionary landscape of these cancers, including role metastatic axillary lymph nodes (ALNs) in seeding distant organ metastasis, can provide a rational basis for effective treatments. Here, we have described genomic analyses primary tumors and lesions from 99 samples obtained 20 patients with cancer. Our revealed diverse spreading patterns that govern tumor progression. Although linear evolution to successive sites was...
Adenosine-to-inosine (A-to-I) RNA editing targets double-stranded stem-loop structures in the mammalian brain. It has previously been shown that miRNAs are substrates for A-to-I editing. For first time, we show several definitions of edited miRNA, level increases with development, thereby indicating a regulatory role during brain maturation. We use high-throughput sequencing to determine levels mature from mouse transcriptome, and compare these pri-miRNA. increased development gradually...
Abstract Motivation: Comparative genomics in general and orthology analysis particular are becoming increasingly important parts of gene function prediction. Previously, reconciliation has been performed only with respect to the parsimony model. This discards many plausible solutions sometimes precludes finding correct one. In other areas bioinformatics probabilistic models have proven be both more realistic powerful than models. For instance, they allow for assessing solution reliability...
Gene tree and species reconstruction, orthology analysis reconciliation, are problems important in multigenome-based comparative genomics biology general. In the present paper, we advance frontier of these areas several respects provide computational tools. First, exact algorithms given for probabilistic reconciliation with respect to gene evolution model, previously developed by authors. Until now, those were solved MCMC estimation algorithms. Second, extend model sequence including...
Phylogeny is both a fundamental tool in biology and rich source of fascinating modeling algorithmic problems. Today's wealth sequenced genomes makes it increasingly important to understand evolutionary events such as duplications, losses, transpositions, inversions, lateral transfers, domain shuffling. We focus on the gene duplication event, that constitutes major force creation genes with new function [Ohno 1970; Lynch Force 2000] and, thereby also, biodiversity. introduce probabilistic...
Lateral gene transfer (LGT)—which transfers DNA between two non-vertically related individuals belonging to the same or different species—is recognized as a major force in prokaryotic evolution, and evidence of its impact on eukaryotic evolution is ever increasing. LGT has attracted much public attention for potential pathogenic elements antibiotic resistance bacteria, pesticide from genetically modified crops other plants. In wider perspective, there growing body studies highlighting role...
This paper develops a model for lateral gene transfer events (a.k.a. horizontal events) between set of trees T1, T2, …, Tk and species tree S. To the best our knowledge, this possesses higher degree biological mathematical soundness than any other proposed in literature. Among considerations, respects partial order evolution implied by Within model, we identify an activity parameter that measures number genes are allowed to be simultaneously active genome taxa show finding most parsimonious...
We consider the problem of constructing a species tree given number gene trees. In frameworks introduced by Goodman et al. [3], Page [10], and Guigó, Muchnik, Smith [5] this is formulated as an optimization problem; namely, that finding requiring minimum duplications and/ or losses in order to explain
According to current estimates there exist about 20,000 pseudogenes in a mammalian genome. The vast majority of these are disabled and nonfunctional copies protein-coding genes which, therefore, evolve neutrally. Recent findings that Makorin1 pseudogene, residing on mouse Chromosome 5, is, indeed, vivo vital also evolutionarily preserved, encouraged us conduct genome-wide survey for other functional human, mouse, chimpanzee. We identify our knowledge the first examples conserved common human...
Abstract Spatial transcriptomics maps gene expression across tissues, posing the challenge of determining spatial arrangement different cell types. However, spots contain multiple cells. Therefore, observed signal comes from mixtures cells Here, we propose an innovative probabilistic model, Celloscope, that utilizes established prior knowledge on marker genes for type deconvolution data. Celloscope outperforms other methods simulated data, successfully indicates known brain structures and...
Cancer can be a result of accumulation different types genetic mutations such as copy number aberrations. The data from tumors are cross-sectional and do not contain the temporal order events. Finding in which events have occurred progression pathways vital importance understanding disease. In to model cancer progression, we propose Progression Networks, special case Bayesian networks, that tailored disease progression. networks similarities with Conjunctive Networks (CBNs) [1],a variation...
Abstract Background PrIME-GenPhyloData is a suite of tools for creating realistic simulated phylogenetic trees, in particular families homologous genes. It supports generation trees based on birth-death process and—perhaps more interestingly—also gene family guided by known (synthetic or biological) species tree while accounting events such as duplication, loss, and lateral transfer (LGT). The also wide range branch rate models enabling relaxation the molecular clock. Result Simulated data...
Abstract Functional characterization of the cancer clones can shed light on evolutionary mechanisms driving cancer’s proliferation and relapse mechanisms. Single-cell RNA sequencing data provide grounds for understanding functional state as a whole; however, much research remains to identify reconstruct clonal relationships toward characterizing changes in functions individual clones. We present PhylEx that integrates bulk genomics with co-occurrences mutations from single-cell high-fidelity...