A5035497488- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Evolution and Genetic Dynamics
- HIV Research and Treatment
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- HIV/AIDS drug development and treatment
- Genomics and Phylogenetic Studies
- HIV/AIDS Research and Interventions
- RNA and protein synthesis mechanisms
- Genetic factors in colorectal cancer
- Gene Regulatory Network Analysis
- Bacteriophages and microbial interactions
- SARS-CoV-2 and COVID-19 Research
- Genomics and Chromatin Dynamics
- Acute Myeloid Leukemia Research
- Plant Virus Research Studies
- Advanced biosensing and bioanalysis techniques
- RNA Research and Splicing
- SARS-CoV-2 detection and testing
- Genetics, Bioinformatics, and Biomedical Research
- Cell Image Analysis Techniques
- Bayesian Methods and Mixture Models
- CRISPR and Genetic Engineering
- Molecular Biology Techniques and Applications
SIB Swiss Institute of Bioinformatics
2016-2025
ETH Zurich
2016-2025
Radboud University Nijmegen
2023
The Geneva Association
2022-2023
Radboud University Medical Center
2023
University Hospital of Basel
2022
University of Basel
2016-2022
École Polytechnique Fédérale de Lausanne
2019-2020
ORCID
2018
Board of the Swiss Federal Institutes of Technology
2008-2017
Summary: ROCR is a package for evaluating and visualizing the performance of scoring classifiers in statistical language R. It features over 25 measures that can be freely combined to create two-dimensional curves. Standard methods investigating trade-offs between specific are available within uniform framework, including receiver operating characteristic (ROC) graphs, precision/recall plots, lift charts cost integrates tightly with R's powerful graphics capabilities, thus allowing highly...
We show that the times separating birth of benign, invasive, and metastatic tumor cells can be determined by analysis mutations they have in common. When combined with prior clinical observations, these analyses suggest following general conclusions about colorectal tumorigenesis: (i) It takes approximately 17 years for a large benign to evolve into an advanced cancer but <2 within acquire ability metastasize; (ii) it requires few, if any, selective events transform highly invasive cell one...
Gut bacteria can affect key aspects of host fitness, such as development, fecundity, and lifespan, while the host, in turn, shapes gut microbiome. However, it is unclear to what extent individual species versus community interactions within microbiome are linked fitness. Here, we combinatorially dissect natural Drosophila melanogaster reveal that between shape fitness through life history tradeoffs. Empirically, made germ-free flies colonized with each possible combination five core fly...
Cancer results from genetic alterations that disturb the normal cooperative behavior of cells. Recent high-throughput genomic studies cancer cells have shown mutational landscape is complex and individual cancers may evolve through mutations in as many 20 different cancer-associated genes. We use data published by Sjöblom et al. (2006) to develop a new mathematical model for somatic evolution colorectal cancers. employ Wright-Fisher process exploring basic parameters this evolutionary derive...
Personalized, precision, P4, or stratified medicine is understood as a medical approach in which patients are based on their disease subtype, risk, prognosis, treatment response using specialized diagnostic tests. The key idea to base decisions individual patient characteristics, including molecular and behavioral biomarkers, rather than population averages. Personalized deeply connected dependent data science, specifically machine learning (often named Artificial Intelligence the mainstream...
Understanding the mutational heterogeneity within tumors is a keystone for development of efficient cancer therapies. Here, we present SCITE, stochastic search algorithm to identify evolutionary history tumor from noisy and incomplete mutation profiles single cells. SCITE comprises flexible Markov chain Monte Carlo sampling scheme that allows user compute maximum-likelihood history, sample posterior probability distribution, estimate error rates underlying sequencing experiments. Evaluation...
With next-generation sequencing technologies, experiments that were considered prohibitive only a few years ago are now possible. However, while these technologies have the ability to produce enormous volumes of data, sequence reads prone error. This poses fundamental hurdles when genetic diversity is investigated. We developed ShoRAH, computational method for quantifying in mixed sample and identifying individual clones population, accounting errors. The software was run on simulated data...
Abstract Clonal diversity is a consequence of cancer cell evolution driven by Darwinian selection. Precise characterization clonal architecture essential to understand the evolutionary history tumor development and its association with treatment resistance. Here, using single-cell DNA sequencing, we report mutational histories 123 acute myeloid leukemia (AML) patients. The data reveals cell-level mutation co-occurrence enables reconstruction characterized linear branching patterns evolution,...
Eubacterium hallii is considered an important microbe in regard to intestinal metabolic balance due its ability utilize glucose and the fermentation intermediates acetate lactate, form butyrate hydrogen. Recently, we observed that E. capable of metabolizing glycerol 3-hydroxypropionaldehyde (3-HPA, reuterin) with reported antimicrobial properties. The key enzyme for 3-HPA conversion cobalamin-dependent glycerol/diol dehydratase PduCDE which also utilizes 1,2-propanediol (1,2-PD) propionate....
Many viruses, including the clinically relevant RNA viruses HIV (human immunodeficiency virus) and HCV (hepatitis C virus), exist in large populations display high genetic heterogeneity within between infected hosts. Assessing intra-patient viral diversity is essential for understanding evolutionary dynamics of designing effective vaccines, success antiviral therapy. Next-generation sequencing (NGS) technologies allow rapid cost-effective acquisition thousands to millions short DNA sequences...
Intra-tumor heterogeneity poses substantial challenges for cancer treatment. A tumor's composition can be deduced by reconstructing its mutational history. Central to current approaches is the infinite sites assumption that every genomic position only mutate once over lifetime of a tumor. The validity this has never been quantitatively assessed. We developed rigorous statistical framework test with single-cell sequencing data. Our accounts high noise and contamination present in such found...
Forward genetic screens with genome-wide CRISPR libraries are powerful tools for resolving cellular circuits and signaling pathways. Applying this technology to organoids, however, has been hampered by technical limitations. Here we report improved accuracy robustness pooled-library capturing sgRNA integrations in single substantially reducing required cell numbers genome-scale screening. We applied our approach wild-type APC mutant human intestinal organoids identify genes involved...
Abstract The continuing emergence of SARS-CoV-2 variants concern and interest emphasizes the need for early detection epidemiological surveillance novel variants. We used genomic sequencing 122 wastewater samples from three locations in Switzerland to monitor local spread B.1.1.7 (Alpha), B.1.351 (Beta) P.1 (Gamma) at a population level. devised bioinformatics method named COJAC (Co-Occurrence adJusted Analysis Calling) that uses read pairs carrying multiple variant-specific signature...
Therapeutic success of anti-HIV therapies is limited by the development drug resistant viruses. These genetic variants display complex mutational patterns in their pol gene, which codes for protease and reverse transcriptase, molecular targets current antiretroviral therapy. Genotypic resistance testing depends on ability to interpret such sequence data, whereas phenotypic directly measures relative vitro susceptibility a drug. From set 650 matched genotype-phenotype pairs we construct...
Drug resistance testing has been shown to be beneficial for clinical management of HIV type 1 infected patients. Whereas phenotypic assays directly measure drug resistance, the commonly used genotypic provide only indirect evidence major challenge being interpretation sequence information. We analyzed significance variations in protease and reverse transcriptase genes derived models that predict from genotypes. For 14 antiretroviral drugs, both data 471 isolates were with a machine learning...
The diversity of virus populations within single infected hosts presents a major difficulty for the natural immune response as well vaccine design and antiviral drug therapy. Recently developed pyrophosphate based sequencing technologies (pyrosequencing) can be used quantifying this by ultra-deep samples. We present computational methods analysis such sequence data apply these techniques to pyrosequencing obtained from HIV patients harboring resistant strains. Our main result is estimation...
Next-generation sequencing technologies can be used to analyse genetically heterogeneous samples at unprecedented detail. The high coverage achievable with these methods enables the detection of many low-frequency variants. However, errors complicate analysis mixed populations and result in inflated estimates genetic diversity. We developed a probabilistic Bayesian approach minimize effect on minority applied it pyrosequencing data obtained from 1.5‐kb-fragment HIV-1 gag/pol gene two control...