Biomedical subjects

Peter F Stadler

Publications and source records attributed to Peter F Stadler.

At least 19 recordsLinked to original sources

PubMed2026

REvolutionH-tl 2.0: A fast and robust tool for decoding evolutionary gene histories.

REvolutionH-tl is a fast, scalable, and integrated software platform for inferring orthology relationships, gene trees, species trees, and reconciled evolutionary scenarios directly from sequence data. Built upon the formal framework of best match graphs (BMGs), REvolutionH-tl predicts orthogroups and orthologous gene pairs with high accuracy, requiring neither precomputed trees nor multiple external tools. The software reconstructs event-labeled gene and species trees, seamlessly integrating reconciliation to produce fast, accurate, and biologically insightful evolutionary scenarios. Through extensive benchmarking on synthetic datasets with known ground truth, REvolutionH-tl outperforms or matches the accuracy of established tools such as OrthoFinder, Proteinortho, RAxML, GeneRax, and RANGER-DTL, while achieving significantly lower runtimes. A key innovation of REvolutionH-tl is its built-in support for detailed, publication-ready visualizations, which allow users to explore genome evolution dynamics, orthogroup composition, and reconciliation results with clarity and ease. These visual features position REvolutionH-tl as the first platform of its kind to combine analytical precision with intuitive interpretability. The software is open-source, cross-platform, and freely available at https://pypi.org/project/revolutionhtl/, providing a robust solution for large-scale evolutionary analyses in comparative genomics.

Software↗

PubMed2025

Recently Evolved, Stage-Specific Genes Are Enriched at Life-Stage Transitions in Flies.

Understanding how genomic information is selectively utilized across different life stages is essential for deciphering the developmental and evolutionary strategies of metazoans. In holometabolous insects, the dynamic expression of genes enables distinct functional adaptations at embryonic, larval, pupal, and adult stages, likely contributing to their evolutionary success. While Drosophila melanogaster (D. melanogaster) has been extensively studied, less is known about the evolutionary dynamics that could govern stage-specific gene expression. To address this question, we compared the distribution of stage-specific genes, that is, genes expressed in temporally restricted developmental stages, across the development of D. melanogaster and Aedes aegypti (A. aegypti). Using tau-scoring, a computational method to determine gene expression specificity, we found that, on average, a large proportion of genes (20%-30% of all protein-coding genes) in both species exhibit restricted expression to specific developmental stages. Phylostratigraphy analysis, a method to date the age of genes, further revealed that stage-specific genes fall into two major categories: highly conserved and recently evolved. Notably, many of the recently evolved and stage-specific genes identified in A. aegypti and D. melanogaster are restricted to Diptera order (20%-35% of all stage-specific genes), highlighting ongoing evolutionary processes that continue to shape life-stage transitions. Overall, our findings underscore the complex interplay between gene evolutionary age, expression specificity, and morphological transformations in development. These results suggest that the attraction of genes to critical life-stage transitions is an ongoing process that may not be constant across evolutionary time or uniform between different lineages, offering new insights into the adaptability and diversification of dipteran genomes.

Animals↗

PubMed2007

PCR survey of hox genes in the goldfish Carassius auratus auratus.

A tetraploidization event took place in the cyprinid lineage leading to goldfishes about 15 million years ago. A PCR survey for Hox genes in the goldfish Carassius auratus auratus (Actinopterygii: Cyprinidae) was performed to assess the consequences of this genome duplication. Not surprisingly, the genomic organization of the Hox gene clusters of goldfish is similar to that of the closely related zebrafish (Danio rerio). However, the goldfish exhibits a much larger number of recent pseudogenes, which are characterized by indels. These findings are consistent with the hypothesis that dosage effects cause selection pressure to rapidly silence crucial developmental regulators after a tetraploidization event.

Animals↗

PubMed2007

RNAs everywhere: genome-wide annotation of structured RNAs.

Starting with the discovery of microRNAs and the advent of genome-wide transcriptomics, non-protein-coding transcripts have moved from a fringe topic to a central field research in molecular biology. In this contribution we review the state of the art of "computational RNomics", i.e., the bioinformatics approaches to genome-wide RNA annotation. Instead of rehashing results from recently published surveys in detail, we focus here on the open problem in the field, namely (functional) annotation of the plethora of putative RNAs. A series of exploratory studies are used to provide non-trivial examples for the discussion of some of the difficulties.

Biological Evolution↗

PubMed2006

Evolution of the vertebrate ParaHox clusters.

The ParaHox cluster contains three Hox-related homeobox genes. The evolution of this sister of the Hox-gene clusters has been studied extensively in metazoans with a focus on its early evolution. Its fate within the vertebrate lineage, and in particular following the teleost-specific genome duplication, however, has not received much attention. Three of the four human ParaHox loci are linked with PDGFR family tyrosine kinases. We demonstrate that these loci arose as duplications in an ancestral vertebrate and trace the subsequent history of gene losses. Surprisingly, teleost fishes have not expanded their ParaHox repertoire following the teleost-specific genome duplication, while duplicates of the associated tyrosine kinases have survived, supporting the hypothesis of a large-scale duplication followed by extensive gene loss.

Animals↗

PubMed2006

Modeling amino acid substitution patterns in orthologous and paralogous genes.

We study to what degree patterns of amino acid substitution vary between genes using two models of protein-coding gene evolution. The first divides the amino acids into groups, with one substitution rate for pairs of residues in the same group and a second for those in differing groups. Unlike previous applications of this model, the groups themselves are estimated from data by simulated annealing. The second model makes substitution rates a function of the physical and chemical similarity between two residues. Because we model the evolution of coding DNA sequences as opposed to protein sequences, artifacts arising from the differing numbers of nucleotide substitutions required to bring about various amino acid substitutions are avoided. Using 10 alignments of related sequences (five of orthologous genes and five gene families), we do find differences in substitution patterns. We also find that, although patterns of amino acid substitution vary temporally within the history of a gene, variation is not greater in paralogous than in orthologous genes. Improved understanding of such gene-specific variation in substitution patterns may have implications for applications such as sequence alignment and phylogenetic inference.

Actins↗

PubMed2006

Prediction of structured non-coding RNAs in the genomes of the nematodes Caenorhabditis elegans and Caenorhabditis briggsae.

We present a survey for non-coding RNAs and other structured RNA motifs in the genomes of Caenorhabditis elegans and Caenorhabditis briggsae using the RNAz program. This approach explicitly evaluates comparative sequence information to detect stabilizing selection acting on RNA secondary structure. We detect 3,672 structured RNA motifs, of which only 678 are known non-translated RNAs (ncRNAs) or clear homologs of known C. elegans ncRNAs. Most of these signals are located in introns or at a distance from known protein-coding genes. With an estimated false positive rate of about 50% and a sensitivity on the order of 50%, we estimate that the nematode genomes contain between 3,000 and 4,000 RNAs with evolutionary conserved secondary structures. Only a small fraction of these belongs to the known RNA classes, including tRNAs, snoRNAs, snRNAs, or microRNAs. A relatively small class of ncRNA candidates is associated with previously observed RNA-specific upstream elements.

Animals↗

PubMed2006

Hairpins in a Haystack: recognizing microRNA precursors in comparative genomics data.

UNLABELLED: Recently, genome-wide surveys for non-coding RNAs have provided evidence for tens of thousands of previously undescribed evolutionary conserved RNAs with distinctive secondary structures. The annotation of these putative ncRNAs, however, remains a difficult problem. Here we describe an SVM-based approach that, in conjunction with a non-stringent filter for consensus secondary structures, is capable of efficiently recognizing microRNA precursors in multiple sequence alignments. The software was applied to recent genome-wide RNAz surveys of mammals, urochordates, and nematodes. AVAILABILITY: The program RNAmicro is available as source code and can be downloaded from http://www.bioinf.uni-leipzig/Software/RNAmicro.

Algorithms↗

PubMed2006

Multiple sequence alignment with user-defined anchor points.

BACKGROUND: Automated software tools for multiple alignment often fail to produce biologically meaningful results. In such situations, expert knowledge can help to improve the quality of alignments. RESULTS: Herein, we describe a semi-automatic version of the alignment program DIALIGN that can take pre-defined constraints into account. It is possible for the user to specify parts of the sequences that are assumed to be homologous and should therefore be aligned to each other. Our software program can use these sites as anchor points by creating a multiple alignment respecting these constraints. This way, our alignment method can produce alignments that are biologically more meaningful than alignments produced by fully automated procedures. As a demonstration of how our method works, we apply our approach to genomic sequences around the Hox gene cluster and to a set of DNA-binding proteins. As a by-product, we obtain insights about the performance of the greedy algorithm that our program uses for multiple alignment and about the underlying objective function. This information will be useful for the further development of DIALIGN. The described alignment approach has been integrated into the TRACKER software system.

Journal Article↗

PubMed2006

Partition function and base pairing probabilities of RNA heterodimers.

BACKGROUND: RNA has been recognized as a key player in cellular regulation in recent years. In many cases, non-coding RNAs exert their function by binding to other nucleic acids, as in the case of microRNAs and snoRNAs. The specificity of these interactions derives from the stability of inter-molecular base pairing. The accurate computational treatment of RNA-RNA binding therefore lies at the heart of target prediction algorithms. METHODS: The standard dynamic programming algorithms for computing secondary structures of linear single-stranded RNA molecules are extended to the co-folding of two interacting RNAs. RESULTS: We present a program, RNAcofold, that computes the hybridization energy and base pairing pattern of a pair of interacting RNA molecules. In contrast to earlier approaches, complex internal structures in both RNAs are fully taken into account. RNAcofold supports the calculation of the minimum energy structure and of a complete set of suboptimal structures in an energy band above the ground state. Furthermore, it provides an extension of McCaskill's partition function algorithm to compute base pairing probabilities, realistic interaction energies, and equilibrium concentrations of duplex structures.

Journal Article↗

PubMed2006

New journal: Algorithms for Molecular Biology.

This editorial announces Algorithms for Molecular Biology, a new online open access journal published by BioMed Central. By launching the first open access journal on algorithmic bioinformatics, we provide a forum for fast publication of high-quality research articles in this rapidly evolving field. Our journal will publish thoroughly peer-reviewed papers without length limitations covering all aspects of algorithmic data analysis in computational biology. Publications in Algorithms for Molecular Biology are easy to find, highly visible and tracked by organisations such as PubMed. An established online submission system makes a fast reviewing procedure possible and enables us to publish accepted papers without delay. All articles published in our journal are permanently archived by PubMed Central and other scientific archives. We are looking forward to receiving your contributions.

Editorial↗

PubMed2006

The expansion of the metazoan microRNA repertoire.

BACKGROUND: MicroRNAs have been identified as crucial regulators in both animals and plants. Here we report on a comprehensive comparative study of all known miRNA families in animals. We expand the MicroRNA Registry 6.0 by more than 1000 new homologs of miRNA precursors whose expression has been verified in at least one species. Using this uniform data basis we analyze their evolutionary history in terms of individual gene phylogenies and in terms of preservation of genomic nearness across species. This allows us to reliably identify microRNA clusters that are derived from a common transcript. RESULTS: We identify three episodes of microRNA innovation that correspond to major developmental innovations: A class of about 20 miRNAs is common to protostomes and deuterostomes and might be related to the advent of bilaterians. A second large wave of innovations maps to the branch leading to the vertebrates. The third significant outburst of miRNA innovation coincides with placental (eutherian) mammals. In addition, we observe the expected expansion of the microRNA inventory due to genome duplications in early vertebrates and in an ancestral teleost. The non-local duplications in the vertebrate ancestor are predated by local (tandem) duplications leading to the formation of about a dozen ancient microRNA clusters. CONCLUSION: Our results suggest that microRNA innovation is an ongoing process. Major expansions of the metazoan miRNA repertoire coincide with the advent of bilaterians, vertebrates, and (placental) mammals.

Animals↗

PubMed2006

Algebraic comparison of metabolic networks, phylogenetic inference, and metabolic innovation.

BACKGROUND: Comparison of metabolic networks is typically performed based on the organisms' enzyme contents. This approach disregards functional replacements as well as orthologies that are misannotated. Direct comparison of the structure of metabolic networks can circumvent these problems. RESULTS: Metabolic networks are naturally represented as directed hypergraphs in such a way that metabolites are nodes and enzyme-catalyzed reactions form (hyper)edges. The familiar operations from set algebra (union, intersection, and difference) form a natural basis for both the pairwise comparison of networks and identification of distinct metabolic features of a set of algorithms. We report here on an implementation of this approach and its application to the procaryotes. CONCLUSION: We demonstrate that metabolic networks contain valuable phylogenetic information by comparing phylogenies obtained from network comparisons with 16S RNA phylogenies. The algebraic approach to metabolic networks is suitable to study metabolic innovations in two sets of organisms, free living microbes and Pyrococci, as well as obligate intracellular pathogens.

Algorithms↗

PubMed2006

Statistics of cycles in large networks.

The occurrence of self-avoiding closed paths (cycles) in networks is studied under varying rules of wiring. As a main result, we find that the dependence between network size and typical cycle length is algebraic, (h) proportional to Nalpha, with distinct values of for different wiring rules. The Barabasi-Albert model has alpha=1. Different preferential and nonpreferential attachment rules and the growing Internet graph yield alpha<1. Computation of the statistics of cycles at arbitrary length is made possible by the introduction of an efficient sampling algorithm.

Journal Article↗

PubMed2006

Memory efficient folding algorithms for circular RNA secondary structures.

BACKGROUND: A small class of RNA molecules, in particular the tiny genomes of viroids, are circular. Yet most structure prediction algorithms handle only linear RNAs. The most straightforward approach is to compute circular structures from 'internal' and 'external' substructures separated by a base pair. This is incompatible, however, with the memory-saving approach of the Vienna RNA Package which builds a linear RNA structure from shorter (internal) structures only. RESULT: Here we describe how circular secondary structures can be obtained without additional memory requirements as a kind of 'post-processing' of the linear structures. AVAILABILITY: The circular folding algorithm is implemented in the current version of the of RNAfold program of the Vienna RNA Package, which can be downloaded from http://www.tbi.univie.ac.at/RNA/

Algorithms↗

PubMed2006

Thermodynamics of RNA-RNA binding.

BACKGROUND: Reliable prediction of RNA-RNA binding energies is crucial, e.g. for the understanding on RNAi, microRNA-mRNA binding and antisense interactions. The thermodynamics of such RNA-RNA interactions can be understood as the sum of two energy contributions: (1) the energy necessary to 'open' the binding site and (2) the energy gained from hybridization. METHODS: We present an extension of the standard partition function approach to RNA secondary structures that computes the probabilities Pu[i, j] that a sequence interval [i, j] is unpaired. RESULTS: Comparison with experimental data shows that Pu[i, j] can be applied as a significant determinant of local target site accessibility for RNA interference (RNAi). Furthermore, these quantities can be used to rigorously determine binding free energies of short oligomers to large mRNA targets. The resource consumption is comparable with a single partition function computation for the large target molecule. We can show that RNAi efficiency correlates well with the binding energies of siRNAs to their respective mRNA target. AVAILABILITY: RNAup will be distributed as part of the Vienna RNA Package, www.tbi.univie.ac.at/~ivo/RNA/

Algorithms↗

PubMed2006

miRNAMap: genomic maps of microRNA genes and their target genes in mammalian genomes.

Recent work has demonstrated that microRNAs (miRNAs) are involved in critical biological processes by suppressing the translation of coding genes. This work develops an integrated database, miRNAMap, to store the known miRNA genes, the putative miRNA genes, the known miRNA targets and the putative miRNA targets. The known miRNA genes in four mammalian genomes such as human, mouse, rat and dog are obtained from miRBase, and experimentally validated miRNA targets are identified in a survey of the literature. Putative miRNA precursors were identified by RNAz, which is a non-coding RNA prediction tool based on comparative sequence analysis. The mature miRNA of the putative miRNA genes is accurately determined using a machine learning approach, mmiRNA. Then, miRanda was applied to predict the miRNA targets within the conserved regions in 3'-UTR of the genes in the four mammalian genomes. The miRNAMap also provides the expression profiles of the known miRNAs, cross-species comparisons, gene annotations and cross-links to other biological databases. Both textual and graphical web interface are provided to facilitate the retrieval of data from the miRNAMap. The database is freely available at http://mirnamap.mbc.nctu.edu.tw/.

Animals↗

PubMed2006

Evolution of microRNAs.

MicroRNAs (miRNAs) form a large class of small regulatory RNAs in eukaryotes. Although they share a common processing pathway and certain structural features, in general, there is no detectable sequence similarity among miRNAs from a given organism. On the other hand, many miRNAs are members of a family of a few, often very similar, paralogs. It is, thus, of interest to trace the evolutionary history of individual miRNAs, to identify the timing of gene duplications, and to study relationships between the histories of different miRNA families. Some miRNAs are transcribed from polycistronic primary transcripts. In these cases, we will study the evolution of entire clusters.

Base Pairing↗