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Rosvall, M.

Publications and source records attributed to Rosvall, M..

7 recordsLinked to original sources

IsoformMapper: A Web Application for Protein-Level Comparison of Splice Variants through Structural Community Analysis

Alternative splicing (AS) plays a key role in numerous cellular processes by enabling the existence of different protein isoforms with potentially different functions and fine-tuning isoform abundance. However, despite its biological importance, tools to compare the domain composition of AS-derived protein isoforms have lagged as they require both structural data and an appropriate methodology for isoform comparison. Recent advances in AI-driven protein structure prediction, particularly AlphaFold2, have made accurate structural determination of splicing isoforms easily accessible, paving the way for new tools to compare their structures and asses the functional consequences of AS at the protein structure level. Here, we present IsoformMapper, a web resource that enables researchers to study alternative splicing at the protein structural level using protein network community analysis, which captures 3D physical interactions between protein regions often missed by traditional domain analysis, allowing comparisons of isoforms across any biological system. As a proof of concept, we used our tool to a case study, in which we studied how GENOMES UNCOUPLED1 (GUN1) dependent retrograde signaling regulates plant de-etiolation through alternative splicing in Arabidopsis. In response to light, we demonstrate that GUN1 regulates the expression of specific spliceosome components, consequently modifying alternative splicing of key genes encoding components essential for establishing of photosynthesis. Additionally, the gun1 mutant showed altered splice variant ratios for PNSL2, CHAOS, and SIG5. Our tool revealed that these isoforms have significantly different protein community structures, illustrating the impact of AS on protein function and demonstrating the practical value of the tool. (247 words) O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/641708v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@c006dcorg.highwire.dtl.DTLVardef@1025b07org.highwire.dtl.DTLVardef@1a64bf6org.highwire.dtl.DTLVardef@c512af_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract.C_FLOATNO IsoformMapper enables structural comparison of protein isoforms through a multi-step analysis pipeline. Starting with AlphaFold2 protein structure predictions of splice variants, the method generates weighted network representations for each isoform. The web application processes multiple AlphaFold predictions per isoform, with the conformational variability between predictions represented as weighted edges in the network representation. These networks are then analyzed using the InfoMap community detection algorithm to identify structural communities, ultimately allowing visualization and comparison of protein isoform structures through interactive network displays and alluvial diagrams. The method is applicable to protein isoforms from any biological system, providing comprehensive analysis of alternative splicing consequences at the protein level by examining structural domains as integrated units. This holistic approach enables users to evaluate potential functional differences between isoforms based on their structural organization. C_FIG

bioinformatics↗

Pseudomonas syringae infectivity correlates to altered transcript and metabolite levels of Arabidopsis Mediator mutants

Rapid metabolic responses to pathogens are essential for plant survival and depend on numerous transcription factors. Mediator is the major transcriptional co-regulator for integration and transmission of signals from transcriptional regulators to RNA polymerase II. Using four Arabidopsis Mediator mutants, med16, med18, med25 and cdk8, we studied how differences in regulation of their transcript and metabolite levels correlate to their responses to Pseudomonas syringae infection. We found that med16 and cdk8 were susceptible, while med25 showed increased resistance. Glucosinolate, phytoalexin and carbohydrate levels were reduced already before infection in med16 and cdk8, but increased in med25, which also displayed increased benzenoids levels. Early after infection, wild type plants showed reduced glucosinolate and nucleoside levels, but increases in amino acids, benzenoids, oxylipins and the phytoalexin Camalexin. The Mediator mutants showed altered levels of these metabolites and in regulation of genes encoding key enzymes for their metabolism. At later stage, mutants displayed defective levels of specific amino acids, carbohydrates, lipids and jasmonates which correlated to their infection response phenotypes. Our results reveal that MED16, MED25 and CDK8 are required for a proper, coordinated transcriptional response of genes which encode enzymes involved in important metabolic pathways for Arabidopsis responses to Pseudomonas syringae infections. HIGHLIGHTPlants need to defend themselves against different types of infections. We show that subunits of the Mediator transcriptional coactivator coordinate metabolic responses of Arabidopsis thaliana to infections by Pseudomonas syringae.

plant biology↗

A natural history of networks: Higher-order network modeling for paleobiology research

Paleobiologists are increasingly employing network-based methods to analyze the complex data retrieved from geohistorical records, including stratigraphic sections, sediments, and fossil collections. However, the lack of a common framework for designing, performing, evaluating, and communicating these studies, leads to issues of reproducibility and communicability. The high-dimensional geohistorical data also raises questions about the limitations of standard network approaches, which assume independent interactions between pairs of components. Higher-order network models better suited for the complex relational structure of the geohistorical data provide an opportunity to overcome these challenges. These models can represent temporal and spatial constraints inherent to the biosedimentary record and describe higher-order interactions, capturing more accurate biogeographical, biostratigraphic, and macroevolutionary patterns. Here we describe how to use the Map Equation framework for designing higher-order network models of geohistorical data, address some practical decisions involved in modeling complex dependencies, and discuss critical methodological and conceptual issues that currently make it difficult to compare results across studies in the growing body of network-based paleobiology research. We illustrate different higher-order network representations and models, including multilayers, hypergraphs, and varying Markov times models, using case studies on gradient analysis, bioregionalization, and macroevolution, and delineate future research directions for current challenges in the emerging field of network paleobiology.

paleontology↗

A dynamical perspective to community detection in ecological networks

O_LIAnalysing how species interact in modules is a fundamental problem in network ecology. Theory shows that a modular network structure can reveal underlying dynamic ecological and evolutionary processes, influence dynamics that operate on the network and affect the stability of the ecological system. C_LIO_LIAlthough many ecological networks describe flows, such as biomass flows in food webs or disease trans-mission, most modularity analyses have ignored network flows, which can hinder our understanding of the interplay between structure and dynamics. C_LIO_LIHere we present Infomap, an established method based on network flows to the field of ecological networks. Infomap is a flexible tool that can identify modules in virtually any type of ecological network and is particularly useful for directed, weighted and multilayer networks. We illustrate how Infomap works on all these network types. We also provide a fully documented repository with additional ecological examples. Finally, to help researchers analyse their networks with Infomap, we introduce the open source R package infomapecology. C_LIO_LIAnalysing flow-based modularity is useful across ecology and transcends to other biological and non-biological disciplines. A dynamic approach for detecting modular structure has strong potential to provide new insights into the organisation of ecological networks. C_LI

ecology↗

Low-Latitude Origins of the Four Phanerozoic Evolutionary Faunas

The hypothesis of the Great Evolutionary Faunas is a foundational concept of macroevolutionary research postulating that three global mega-assemblages have dominated Phanerozoic oceans following abrupt biotic transitions. Empirical estimates of this large-scale pattern depend on several methodological decisions and are based on approaches unable to capture multiscale dynamics of the underlying Earth-Life System. Combining a multilayer network representation of fossil data with a multilevel clustering that eliminates the subjectivity inherent to distance-based approaches, we demonstrate that Phanerozoic oceans sequentially harbored four global benthic mega-assemblages. Shifts in dominance patterns among these global marine mega-assemblages are abrupt (end-Cambrian 494 Ma; end-Permian 252 Ma) or protracted (mid-Cretaceous 129 Ma), and represent the three major biotic transitions in Earths history. This finding suggests that the mid-Cretaceous radiation of the so-called Modern evolutionary Fauna, concurrent with gradual ecological changes associated with the Mesozoic Marine Revolution, triggered a biotic transition comparably to the transition following the largest extinction event in the Phanerozoic. Overall, our study supports the notion that both long-term ecological changes and major geological events have played crucial roles in shaping mega-assemblages that dominated Phanerozoic oceans.

paleontology↗

Regularities in species niches reveal the World's climatic regions

Although classifications of the Earths climates date back to the ancient Greeks, the climatic regions shaping the distribution of animals remain poorly resolved. Here we present a classification of global climates based on regularities in realised niches of 3657 amphibians, 7204 reptiles, 10684 birds and 4574 mammals. We found 16 main climatic regions that are mostly consistent across groups and previous plant expert-based classifications, confirming the existence of major climatic restrictions for life. The results also suggest that differences among groups likely relate to their particular adaptations and dispersal capabilities. We further show how the integration of species niche classifications with geographical information provides valuable information on potential mechanisms shaping the climatic regions. Our climate classification has applications in several disciplines, including conservation planning and ecological and evolutionary studies.

ecology↗

Human activity is altering the world’s zoogeographical regions

Human activity leading to both species introductions and extinctions is widely known to influence diversity patterns on local and regional scales. Yet, it is largely unknown whether the intensity of this activity is enough to affect the configuration of biodiversity at broader levels of spatial organization. Zoogeographical regions, or zooregions, are surfaces of the Earth defined by characteristic pools of species, which reflect ecological, historical, and evolutionary processes acting over millions of years. Consequently, it is widely assumed that zooregions are robust and unlikely to change on a human timescale. Here, however, we show that human-mediated introductions and extinctions can indeed reconfigure the currently recognized zooregions of amphibians, mammals, and birds. In particular, introductions homogenize the African and Eurasian zooregions in mammals; reshape boundaries with the reallocation of Oceania to the New World zooregion in amphibians; and divide bird zooregions by increasing biotic heterogeneity. Furthermore, the combined effect of amphibian introductions and extinctions has the potential to divide two zooregions largely representing the Old and the New World. Interestingly, the robustness of zooregions against changes in species composition may largely explain such zoogeographical changes. Altogether, our results demonstrate that human activities can erode the higher-level organization of biodiversity formed over millions of years. Comparable reconfigurations have previously been detectable in Earths history only after glaciations and mass extinction events, highlighting the profound and far-reaching impact of ongoing human activity and the need to protect the uniqueness of biotic assemblages from the effects of future species introductions and extinctions.

ecology↗