A5006646343- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Genetics and Physical Performance
- CAR-T cell therapy research
- Adipose Tissue and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Immune Response and Inflammation
- Mycotoxins in Agriculture and Food
- Peptidase Inhibition and Analysis
- Reproductive Biology and Fertility
- Fungal and yeast genetics research
- Immunotherapy and Immune Responses
- Machine Learning in Bioinformatics
- Animal Genetics and Reproduction
- vaccines and immunoinformatics approaches
- Marine animal studies overview
Technische Universität Dresden
2018-2025
Berlin-Brandenburger Centrum für Regenerative Therapien
2024
Max Planck Institute of Molecular Cell Biology and Genetics
2015-2023
Center for Systems Biology Dresden
2018-2023
Max Planck Institute for the Physics of Complex Systems
2015-2023
University of Limerick
2022-2023
German Center for Diabetes Research
2018-2022
Heinrich Heine University Düsseldorf
2018-2022
Deutsches Diabetes-Zentrum e.V.
2018-2022
Paul Langerhans Institute Dresden
2018-2022
Abstract Identifying the genomic changes that underlie phenotypic adaptations is a key challenge in evolutionary biology and genomics. Loss of protein-coding genes one type change with potential to affect evolution. Here, we develop genomics approach accurately detect gene losses investigate their importance for adaptive evolution mammals. We discover number likely contributed morphological, physiological, metabolic aquatic flying These shed light on possible molecular cellular mechanisms...
Annotating coding genes and inferring orthologs are two classical challenges in genomics evolutionary biology that have traditionally been approached separately, limiting scalability. We present TOGA (Tool to infer Orthologs from Genome Alignments), a method integrates structural gene annotation orthology inference. implements different paradigm orthologous loci, improves ortholog detection of conserved compared with state-of-the-art methods, handles even highly fragmented assemblies. scales...
Many different solutions to predicting the cognate epitope target of a T-cell receptor (TCR) have been proposed. However several questions on advantages and disadvantages these approaches remain unresolved, as most methods only evaluated within context their initial publications data sets. Here, we report findings first public TCR-epitope prediction benchmark performed 23 models in ImmRep 2022 specificity workshop. This revealed that use paired-chain alpha-beta, well CDR1/2 or V/J...
Several genes lost in the ancestors of whales and dolphins likely contributed to adapting a fully aquatic environment.
The repeated evolution of dietary specialization represents a hallmark mammalian ecology. To detect genomic changes that are associated with adaptations, we performed systematic screen for convergent gene losses an obligate herbivorous or carnivorous diet in 31 placental mammals. For herbivores, our discovered the loss triglyceride lipase inhibitor
Descent of testes from a position near the kidneys into lower abdomen or scrotum is an important developmental process that occurs in all placental mammals, with exception five afrotherian lineages. Since soft-tissue structures like are not preserved fossil record and since key parts mammal phylogeny remain controversial, it has been debated whether testicular descent ancestral derived condition mammals. To resolve this debate, we used genomic data 71 mammalian species analyzed evolution two...
Genome alignments provide a powerful basis to transfer gene annotations from well-annotated reference genome many other aligned genomes. The completeness of these crucially depends on the sensitivity underlying alignment. Here, we investigated impact alignment parameters and found that with higher allow detection thousands novel between orthologous exons have been missed before. In particular, comparisons species separated by an evolutionary distance >0.75 substitutions per neutral site,...
Identifying coding genes is an essential step in genome annotation. Here, we utilize existing whole alignments to detect conserved exons and then map gene annotations from one many aligned genomes. We show that contain thousands of spurious frameshifts splice site mutations are truly conserved. To overcome these limitations, have developed CESAR (Coding Exon-Structure Aware Realigner) realigns exons, while considering reading frame sites each exon. effectively avoids detects 91% shifted...
Homology-based gene prediction is a powerful concept to annotate newly sequenced genomes. We have previously demonstrated that whole genome alignments can be utilized for accurate comparative coding annotation.Here we present CESAR 2.0 utilizes transfer annotations from one reference many other aligned show 77 times faster and requires 31 less memory compared its predecessor. substantially improves the ability align splice sites shifted over larger distances, allowing precise identification...
Toll-like receptors (TLRs) play an important role for the innate immune system by detecting pathogen-associated molecular patterns. TLR5 encodes major extracellular receptor bacterial flagellin and frequently evolves under positive selection, consistent with coevolutionary arms races between host pathogens. Furthermore, is inactivated in several vertebrates a stop codon polymorphism widespread human populations. Here, we analyzed genomes of 120 mammals discovered that convergently lost four...
Bacterial genome annotations contain a number of coding sequences (CDSs) that, in spite reading frame disruptions, encode single continuous polypeptide. Such disruptions have different origins: sequencing errors, frameshift, or stop codon mutations, as well instances utilization nontriplet decoding. We extracted over 1,000 CDSs with annotated and found that about 75% them can be clustered into 64 groups based on sequence similarity. Analysis the clusters revealed deep phylogenetic...
Abstract Programmed ribosomal -1 frameshifting is a non-standard decoding process occurring when ribosomes encounter signal embedded in the mRNA of certain eukaryotic and prokaryotic genes. This has mandatory component, frameshift motif: it either Z_ZZN tetramer or X_XXZ_ZZN heptamer (where ZZZ XXX are three identical nucleotides) allowing cognate near-cognate repairing to frame A site P sites tRNAs. Depending on signal, frequency can vary over wide range, from less than 1% more 50%. The...
Kallikrein related peptidase 8 (KLK8; also called neuropsin) is a serine protease that plays distinct roles in the skin and hippocampus. In skin, KLK8 influences keratinocyte proliferation desquamation, activates antimicrobial peptides sweat. hippocampus, affects memory acquisition. Here, we examined evolution of mammals discovered that, out 70 placental mammals, exclusively lost three independent fully-aquatic lineages, comprising dolphin, killer whale, minke manatee. addition, while sperm...
CD8+ T cells are important effectors of adaptive immunity against pathogens, tumors and self antigens. Here, we asked how human cognate antigen-responsive their receptors could be identified in unselected single-cell gene expression data. Single-cell RNA sequencing qPCR dye-labelled antigen-specific large sets that were congruently up- or downregulated virus-responsive under different antigen presentation conditions. Combined TNFRSF9, XCL1, XCL2, CRTAM was the most distinct marker on a...
Abstract Annotating coding genes and inferring orthologs are two classical challenges in genomics evolutionary biology that have traditionally been approached separately, limiting scalability. We present TOGA, a method integrates structural gene annotation orthology inference. TOGA implements different paradigm to infer orthologous loci, improves ortholog detection of conserved compared state-of-the-art methods, handles even highly-fragmented assemblies. scales hundreds genomes, which we...
Abstract Many different solutions to predicting the cognate epitope target of a T-cell receptor (TCR) have been proposed. However several questions on advantages and disadvantages these approaches remain unresolved, as most methods only evaluated within context their initial publications data sets. Here, we report findings first public TCR-epitope prediction benchmark performed 23 models in ImmRep 2022 specificity workshop. This revealed that use paired-chain alpha-beta, well CDR1/2 or V/J...
Significance Perturbation of transcription register by RNA polymerase, slippage, is used to yield additional protein products. Known functionally important cases involve a small number short sequences without secondary structure. The discovery reported here the dependence newly identified motif on nascent forming stem loop structure within exit channel polymerase greatly extends potential for broad variety putative slippage sequences, especially as phenomenon has been observed with both...
Abstract We systematically investigate whether losses of human disease-associated genes occurred in other mammals during evolution. first show that lost any 62 non-human generally have a lower degree pleiotropy, and are highly depleted essential genes. Despite this under-representation, we discovered multiple implicated disease truly mammals. In most cases, traits resembling symptoms present but not deleterious gene-loss species, exemplified by causing eye or teeth disorders poor-vision...
Resting conventional T cells (Tconv) can be distinguished from regulatory (Treg) by the canonical markers FOXP3, CD25 and CD127. However, expression of these proteins alters after T-cell activation leading to overlap between Tconv Treg. The objective this study was distinguish resting antigen-responsive effector Treg using single-cell technologies. CD4+ were stimulated with antigen responsive non-responsive populations processed for targeted non-targeted RNAseq. Machine learning used...