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Mashup Score: 0Predicting pain genes: multi-modal data integration using probabilistic classifiers and interaction networks - 1 hour(s) ago
Accurate identification of pain-related genes remains challenging due to the complex nature of pain pathophysiology and the subjective nature of pain reporting in humans, or inferring pain states in animals on the basis of behaviour. Here, we use a machine learning approach to identify possible pain genes. Labelling was based on a gold-standard list of genes with validated involvement across pain conditions, and was trained on a selection of -omics (eg. transcriptomics, proteomics, etc.), protein-protein interaction (PPI) network features, and biological function readouts for each gene. Multiple classifiers were trained, and the top-performing model was selected to predict a pain score per gene. The top ranked genes were then validated against pain-related human SNPs to validate against human genetics studies. Functional analysis revealed JAK2/STAT3 signal, ErbB, and Rap1 signalling pathways as promising targets for further exploration, while network topological features contribute sig
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Mashup Score: 0
Increasing works for antibody design are emerging to generate sequences and structures in Complementarity Determining Regions (CDRs), but problems still exist. We focus on two of them: (i) authenticity of the generated structure and (ii) rationality of the affinity maturation, and propose GeoAB as a solution. In specific, GeoAB-Designer generates CDR structures with realistic internal geometries, composed of a generative geometry initializer (Geo-Initializer) and a position refiner (Geo-Refiner); GeoAB-Optimizer achieves affinity maturation by accurately predicting both the mutation effects and structures of mutant antibodies with the same network architecture as Geo-Refiner. Experiments show that GeoAB achieves state-of-the-art performance in CDR co-design and mutation effect predictions, and fulfills the discussed tasks effectively. ### Competing Interest Statement The authors have declared no competing interest.
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Mashup Score: 0Clinical considerations on antimicrobial resistance potential of complex microbiological samples - 1 hour(s) ago
Antimicrobial resistance (AMR) is one of our greatest public health challenges. Targeted use of antibiotics (AB) can reduce the occurrence and spread of AMR and boost the effectiveness of treatment. This requires knowledge of the antibiotic susceptibility (AS) of the pathogens involved in the disease. Therapeutic recommendations based on classical antibiotic susceptibility testing (AST) are based on the analysis of only a fraction of the bacteria present in the disease process. Next and third generation sequencing technologies allow the identification of antimicrobial resistance genes (ARGs) present in a bacterial community. Using this genomic approach, we can map the antimicrobial resistance potential (AMRP) of a complex, multi-bacterial microbial sample. Using the same approach, antibiotics without any ARGs in the sample that interferes with their activity can be identified. The same approach can be used to identify antibiotics without any ARGs in the sample that interfere with their
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Mashup Score: 0
Candidatus Accumulibacter is a unique and pivotal genus of polyphosphate-accumulating organisms (PAOs) prevalent in wastewater treatment plants, and plays mainstay roles in the global phosphorus cycle. Whereas, the efforts toward a complete understanding of their genetic and metabolic characteristics are largely hindered by major limitations in existing sequence-based annotation methods, leaving more than half of their protein-encoding genes unannotated. To address the challenge, we developed a comprehensive approach integrating pangenome analysis, gene-based protein structure and function prediction, and metatranscriptomic analysis, extending beyond the constraints of sequence-centric methodologies. The application to Ca. Accumulibacter allowed the establishment of the pan-Ca. Accumulibacter proteome structure database, providing references for >200,000 proteins. Benchmarking on 28 Ca. Accumulibacter genomes showed major increases in the average annotation coverage from 51% to 83%. Ge
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Mashup Score: 0
Genomic structural variants (SVs) play a crucial role in adaptive evolution, yet their average fitness effects and characterization with pangenome tools are understudied in wild animal populations. We constructed a pangenome for House Finches, a model for studies of hostpathogen coevolution, using long-read sequence data on 16 individuals (32 de novo-assembled haplotypes) and one outgroup. We identified 643,207 SVs larger than 50 base pairs, mostly (60%) involving repetitive elements, with reduced SV diversity in the eastern US as a result of its introduction by humans. The distribution of fitness effects of genome-wide SVs was estimated using maximum likelihood approaches and showed SVs in both coding and non-coding regions to be on average more deleterious than smaller indels or single nucleotide polymorphisms. The reference-free pangenome facilitated discovery of a 10-million-year-old, 11-megabase-long pericentric inversion on chromosome 1. We found that the genotype frequencies of
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Mashup Score: 0CMAPLE: efficient phylogenetic inference in the pandemic era - 1 hour(s) ago
We have recently introduced MAPLE (MAximum Parsimonious Likelihood Estimation), a new pandemic-scale phylogenetic inference method exclusively designed for genomic epidemiology. In response to the need for enhancing MAPLE’s performance and scalability, here we present two key components: (1) CMAPLE software, a highly optimized C++ reimplementation of MAPLE with many new features and advancements; and (2) CMAPLE library, a suite of Application Programming Interfaces to facilitate the integration of the CMAPLE algorithm into existing phylogenetic inference packages. Notably, we have successfully integrated CMAPLE into the widely used IQ-TREE 2 software, enabling its rapid adoption in the scientific community. These advancements serve as a vital step towards better preparedness for future pandemics, offering researchers powerful tools for large-scale pathogen genomic analysis. ### Competing Interest Statement The authors have declared no competing interest.
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Mashup Score: 0Comparative genomic analysis identifies potential adaptive variation and virulence factors in Mycoplasma ovipneumoniae - 1 hour(s) ago
Mycoplasma ovipneumoniae is associated with respiratory disease in wild and domestic Caprinae globally, with wide variation in disease outcomes within and between host species. To gain insight into phylogenetic structure and mechanisms of pathogenicity for this bacterial species, we compared M. ovipneumoniae genomes for 99 samples from six countries (Australia, Bosnia and Herzegovina, Brazil, China, France, USA) and four host species (domestic sheep, domestic goats, bighorn sheep, caribou). Core genome sequences of M. ovipneumoniae assemblies from domestic sheep and goats fell into two well-supported phylogenetic clades that are divergent enough to be considered different bacterial species, consistent with each of these two clades having an evolutionary origin in separate host species. Genome assemblies from bighorn sheep and caribou also fell within these two clades, indicating multiple spillover events, most commonly from domestic sheep. Pangenome analysis indicated a high percentage
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Mashup Score: 0WOLO: Wilson Only Looks Once – Estimating ant body mass from reference-free images using deep convolutional neural networks - 1 hour(s) ago
Size estimation is a hard computer vision problem with widespread applications in quality control in manufacturing and processing plants, livestock management, and studies on animal behaviour. Typically, image-based size estimation is facilitated by either well-controlled imaging conditions, the provision of global cues, or both. Reference-free size estimation is challenging, because objects of vastly different sizes can appear identical if they are of similar shape. Here, we attempt to implement automated and reference-free body size estimation to facilitate large-scale experimental work in a key model species in sociobiology: the leaf-cutter ants. Leaf-cutter ants are a suitable testbed for reference-free size-estimation, because their workers differ vastly in both size and shape; in principle, it is therefore possible to infer body mass, a proxy for size, from relative body proportions alone. Inspired by earlier work by E.O. Wilson, who trained himself to discern ant worker size fro
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Mashup Score: 0Tissue growth associated transition of podoplanin-expressing stromal cells in the postnatal mouse femur - 1 hour(s) ago
Skeletal stem/progenitor cells are tissue-resident stem/progenitor cells involved in the formation of the skeletal tissue, bone marrow, and hematopoietic microenvironment. Podoplanin-expressing stromal cells (PDPN-SCs) are skeletal stem/progenitor cell-lineage stromal cells. In the adult mouse bone marrow, PDPN-SCs are present on the diaphyseal arterioles and promote megakaryo/erythropoiesis. However, the localized distribution of PDPN-SCs in neonatal and postnatal femurs remains unclear. In this study, we histologically examined the transition of PDPN-SCs during postnatal femoral growth. In the diaphyseal marrow, PDPN-SCs were present in the neonatal marrow space but disappeared with femoral growth. In the cortical bone, abundant PDPN-SCs existed in the primitive neonatal bone and transitioned to restricted localization in the periosteum and endosteum with tissue growth. In the metaphysis, PDPN-SCs resided in nascent trabecular bones. We also found a novel subset of PDPN-SCs that expr
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Mashup Score: 0
Circadian rhythms are ubiquitous across the kingdoms of life and serve important roles in regulating physiology and behavior at many levels. These rhythms occur in ~24-hour cycles and are driven by a core molecular oscillator. Circadian timekeeping enables organisms to anticipate daily changes by timing their growth and internal processes. Neurospora crassa is a model organism with a long history in circadian biology, having conserved eukaryotic clock properties and observable circadian phenotypes. A core approach for measuring circadian function in Neurospora is to follow daily oscillations in the direction of growth and spore formation along a thin glass tube (race tube). While leveraging robust phenotypic readouts is useful, interpreting the outputs of large-scale race tube experiments by hand can be time-consuming and prone to human error. To provide the field with an efficient tool for analyzing race tubes, we present Rhythmidia, a graphical user interface (GUI) tool written in Py
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Predicting pain genes: multi-modal data integration using probabilistic classifiers and interaction networks https://t.co/bUnVSIjQoW #bioRxiv