A Pan-plant Protein Complex Map Reveals Deep Conservation and Novel Assemblies.
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ABSTRACT:
SUBMITTER: McWhite CD
PROVIDER: S-EPMC7297045 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2011-06-16 | GSE26957 | GEO
Project description:MotivationResidue-residue contact prediction is important for protein structure prediction and other applications. However, the accuracy of current contact predictors often barely exceeds 20% on long-range contacts, falling short of the level required for ab initio structure prediction.ResultsHere, we develop a novel machine learning approach for contact map prediction using three steps of increasing resolution. First, we use 2D recursive neural networks to predict coarse contacts and orientations between secondary structure elements. Second, we use an energy-based method to align secondary structure elements and predict contact probabilities between residues in contacting alpha-helices or strands. Third, we use a deep neural network architecture to organize and progressively refine the prediction of contacts, integrating information over both space and time. We train the architecture on a large set of non-redundant proteins and test it on a large set of non-homologous domains, as well as on the set of protein domains used for contact prediction in the two most recent CASP8 and CASP9 experiments. For long-range contacts, the accuracy of the new CMAPpro predictor is close to 30%, a significant increase over existing approaches.AvailabilityCMAPpro is available as part of the SCRATCH suite at http://scratch.proteomics.ics.uci.edu/.Contactpfbaldi@uci.eduSupplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC3463120 | biostudies-literature
Project description:Eukaryotic cells express several classes of small RNAs that regulate gene expression and ensure genome maintenance. Endogenous siRNAs (endo-siRNAs) and Piwi-interacting RNAs (piRNAs) mainly control gene and transposon expression in the germline, while microRNAs (miRNAs) generally function in post-transcriptional gene silencing in both somatic and germline cells. To provide an evolutionary and developmental perspective on small RNA pathways in nematodes, we identified and characterized known and novel small RNA classes through gametogenesis and embryo development in the parasitic nematode Ascaris suum and compared them with known small RNAs of Caenorhabditis elegans. piRNAs, Piwi-clade Argonautes, and other proteins associated with the piRNA pathway have been lost in Ascaris. miRNAs are synthesized immediately after fertilization in utero, before pronuclear fusion, and before the first cleavage of the zygote. This is the earliest expression of small RNAs ever described at a developmental stage long thought to be transcriptionally quiescent. A comparison of the two classes of Ascaris endo-siRNAs, 22G-RNAs and 26G-RNAs, to those in C. elegans, suggests great diversification and plasticity in the use of small RNA pathways during spermatogenesis in different nematodes. Our data reveal conserved characteristics of nematode small RNAs as well as features unique to Ascaris that illustrate significant flexibility in the use of small RNAs pathways, some of which are likely an adaptation to Ascaris' life cycle and parasitism. The transcriptome assembly has been submitted to NCBI Transcriptome Shotgun Assembly Sequence Database(http://www.ncbi.nlm.nih.gov/genbank/TSA.html) under accession numbers JI163767–JI182837 and JI210738–JI257410.
| S-EPMC3166831 | biostudies-literature
Project description:The DNA damage response (DDR) ensures error-free DNA replication and transcription and is disrupted in numerous diseases. An ongoing challenge is to determine the proteins orchestrating DDR and their organization into complexes, including constitutive interactions and those responding to genomic insult. Here, we use multi-conditional network analysis to systematically map DDR assemblies at multiple scales. Affinity purifications of 21 DDR proteins, with/without genotoxin exposure, are combined with multi-omics data to reveal a hierarchical organization of 605 proteins into 109 assemblies. The map captures canonical repair mechanisms and proposes new DDR-associated proteins extending to stress, transport, and chromatin functions. We find that protein assemblies closely align with genetic dependencies in processing specific genotoxins and that proteins in multiple assemblies typically act in multiple genotoxin responses. Follow-up by DDR functional readouts newly implicates 12 assembly members in double-strand-break repair. The DNA damage response assemblies map is available for interactive visualization and query (ccmi.org/ddram/).
| S-EPMC10330685 | biostudies-literature
Project description:Epstein-Barr virus (EBV) is a complex oncogenic symbiont. The molecular mechanisms governing EBV carcinogenesis remain elusive and the functional interactions between virus and host cells are incompletely defined. Here we present a comprehensive map of the host cell-pathogen interactome in EBV-associated cancers. We systematically analyzed RNA sequencing from >1,000 patients with 15 different cancer types, comparing virus and host factors of EBV+ to EBV- tissues. EBV preferentially integrated at highly accessible regions of the cancer genome, with significant enrichment in super-enhancer architecture. Twelve EBV transcripts, including LMP1 and LMP2, correlated inversely with EBV reactivation signature. Overexpression of these genes significantly suppressed viral reactivation, consistent with a "virostatic" function. In cancer samples, hundreds of novel frequent missense and nonsense variations in virostatic genes were identified, and variant genes failed to regulate their viral and cellular targets in cancer. For example, one-third of patients with EBV+ NK/T-cell lymphoma carried two novel nonsense variants (Q322X, G342X) of LMP1 and both variant proteins failed to restrict viral reactivation, confirming loss of virostatic function. Host cell transcriptional changes in response to EBV infection classified tumors into two molecular subtypes based on patterns of IFN signature genes and immune checkpoint markers, such as PD-L1 and IDO1. Overall, these findings uncover novel points of interaction between a common oncovirus and the human genome and identify novel regulatory nodes and druggable targets for individualized EBV and cancer-specific therapies. SIGNIFICANCE: This study provides a comprehensive map of the host cell-pathogen interactome in EBV+ malignancies.See related commentary by Mbulaiteye and Prokunina-Olsson, p. 5917.
| S-EPMC6891172 | biostudies-literature
Project description:Over millions of years, eukaryotes evolved from unicellular to multicellular organisms with increasingly complex genomes and sophisticated gene expression networks. Consequently, chromatin regulators evolved to support this increased complexity. The ATP-dependent chromatin remodelers of the SWI/SNF family are multiprotein complexes that modulate nucleosome positioning and appear under different configurations, which perform distinct functions. While the composition, architecture, and activity of these subclasses are well understood in a limited number of fungal and animal model organisms, the lack of comprehensive information in other eukaryotic organisms precludes the identification of a reliable evolutionary model of SWI/SNF complexes. Here, we performed a systematic analysis using 36 species from animal, fungal, and plant lineages to assess the conservation of known SWI/SNF subunits across eukaryotes. We identified evolutionary relationships that allowed us to propose the composition of a hypothetical ancestral SWI/SNF complex in the last eukaryotic common ancestor. This last common ancestor appears to have undergone several rounds of lineage-specific subunit gains and losses, shaping the current conformation of the known subclasses in animals and fungi. In addition, our results unravel a plant SWI/SNF complex, reminiscent of the animal BAF subclass, which incorporates a set of plant-specific subunits of still unknown function.
| S-EPMC9170682 | biostudies-literature
Project description:BackgroundWith the advances in the high throughput next generation sequencing technologies, genome-wide association studies (GWAS) have identified a large set of variants associated with complex phenotypic traits at a very fine scale. Despite the progress in GWAS, identification of genotype-phenotype relationship remains challenging in maize due to its nature with dozens of variants controlling the same trait. As the causal variations results in the change in expression, gene expression analyses carry a pivotal role in unraveling the transcriptional regulatory mechanisms behind the phenotypes.ResultsTo address these challenges, we incorporated the gene expression and GWAS-driven traits to extend the knowledge of genotype-phenotype relationships and transcriptional regulatory mechanisms behind the phenotypes. We constructed a large collection of gene co-expression networks and identified more than 2 million co-expressing gene pairs in the GWAS-driven pan-network which contains all the gene-pairs in individual genomes of the nested association mapping (NAM) population. We defined four sub-categories for the pan-network: (1) core-network contains the highest represented ~ 1% of the gene-pairs, (2) near-core network contains the next highest represented 1-5% of the gene-pairs, (3) private-network contains ~ 50% of the gene pairs that are unique to individual genomes, and (4) the dispensable-network contains the remaining 50-95% of the gene-pairs in the maize pan-genome. Strikingly, the private-network contained almost all the genes in the pan-network but lacked half of the interactions. We performed gene ontology (GO) enrichment analysis for the pan-, core-, and private- networks and compared the contributions of variants overlapping with genes and promoters to the GWAS-driven pan-network.ConclusionsGene co-expression networks revealed meaningful information about groups of co-regulated genes that play a central role in regulatory processes. Pan-network approach enabled us to visualize the global view of the gene regulatory network for the studied system that could not be well inferred by the core-network alone.
| S-EPMC9762053 | biostudies-literature
Project description:Beta-proteobacteria belonging to the genus Acidovorax have been described from various environments. Many strains can interact with a range of hosts, including humans and plants, forming neutral, beneficial or detrimental associations. In the frame of this study, we investigated the genomic properties of 52 bacterial strains of the genus Acidovorax, isolated from healthy roots of Lotus japonicus, with the intent of identifying traits important for effective plant-growth promotion. Based on single-strain inoculation bioassays with L. japonicus, performed in a gnotobiotic system, we distinguished seven robust plant-growth promoting strains from strains with no significant effects on plant-growth. We showed that the genomes of the two groups differed prominently in protein families linked to sensing and transport of organic acids, production of phytohormones, as well as resistance and production of compounds with antimicrobial properties. In a second step, we compared the genomes of the tested isolates with those of plant pathogens and free-living strains of the genus Acidovorax sourced from public repositories. Our pan-genomics comparison revealed features correlated with commensal and pathogenic lifestyle. We showed that commensals and pathogens differ mostly in their ability to use plant-derived lipids and in the type of secretion-systems being present. Most free-living Acidovorax strains did not harbour any secretion-systems. Overall, our data indicate that Acidovorax strains undergo extensive adaptations to their particular lifestyle by horizontal uptake of novel genetic information and loss of unnecessary genes.
| S-EPMC8767351 | biostudies-literature
Project description:The functions of the majority of trypanosomatid-specific proteins are unknown, hindering our understanding of the biology and pathogenesis of Trypanosomatida. While protein-protein interactions are highly informative about protein function, a global map of protein interactions and complexes is still lacking for these important human parasites. Here, benefiting from in-depth biochemical fractionation, we systematically interrogated the co-complex interactions of more than 3354 protein groups in procyclic life stage of Trypanosoma brucei, the protozoan parasite responsible for human African trypanosomiasis. Using a rigorous methodology, our analysis led to identification of 128 high-confidence complexes encompassing 716 protein groups, including 635 protein groups that lacked experimental annotation. These complexes correlate well with known pathways as well as for proteins co-expressed across the T. brucei life cycle, and provide potential functions for a large number of previously uncharacterized proteins. We validated the functions of several novel proteins associated with the RNA-editing machinery, identifying a candidate potentially involved in the mitochondrial post-transcriptional regulation of T. brucei. Our data provide an unprecedented view of the protein complex map of T. brucei, and serve as a reliable resource for further characterization of trypanosomatid proteins. The presented results in this study are available at: www.TrypsNetDB.org.
| S-EPMC4798371 | biostudies-literature
Project description:BackgroundTo date genomic studies on Map have concentrated on Type C strains with only a few Type S strains included for comparison. In this study the entire pan-genome of 261 Map genomes (205 Type C, 52 Type S and 4 Type B) and 7 Mycobacterium avium complex (Mac) genomes were analysed to identify genomic similarities and differences between the strains and provide more insight into the evolutionary relationship within this Mycobacterial species.ResultsOur analysis of the core genome of all the Map isolates identified two distinct lineages, Type S and Type C Map that is consistent with previous phylogenetic studies of Map. Pan-genome analysis revealed that Map has a larger accessory genome than Mycobacterium avium subsp. avium (Maa) and Type C Map has a larger accessory genome than Type S Map. In addition, we found large rearrangements within Type S strains of Map and little to none in Type C and Type B strains. There were 50 core genes identified that were unique to Type S Map and there were no unique core genes identified between Type B and Type C Map strains. In Type C Map we identified an additional CE10 CAZyme class which was identified as an alpha/beta hydrolase and an additional polyketide and non-ribosomal peptide synthetase cluster. Consistent with previous analysis no plasmids and only incomplete prophages were identified in the genomes of Map. There were 45 hypothetical CRISPR elements identified with no associated cas genes.ConclusionThis is the most comprehensive comparison of the genomic content of Map isolates to date and included the closing of eight Map genomes. The analysis revealed that there is greater variation in gene synteny within Type S strains when compared to Type C indicating that the Type C Map strain emerged after Type S. Further analysis of Type C and Type B genomes revealed that they are structurally similar with little to no genetic variation and that Type B Map may be a distinct clade within Type C Map and not a different strain type of Map. The evolutionary lineage of Maa and Map was confirmed as emerging after M. hominissuis.
| S-EPMC10619280 | biostudies-literature