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Organisms that live in different environments face different evolutionary pressures. As such, organisms that have more successful phenotypes reproduce more frequently, but differing selective pressures acting at the organismal level can influence genes, and thus proteins. Understanding how proteins adapt across environments may therefore be useful in engineering proteins for specific environments as well as to improve our understanding of basic biology. In this work, we explicitly compare homologous (read: paired) proteins from different environments. While previous studies have explored the relevant evolutionary pressures in one of these environments [11], [17] and genomic responses to those pressures [1], [28], no prior computational study of their proteins has been performed. We apply ESM-2 [20] and although there is no signal in our negative control (two divergent yeast strains) as expected, we obtain near perfect prediction accuracy for our selected environmental gradient–the well-established subsurface vs. surface biome. We further show that ESM-2 is able to capture relevant fine-grained biological patterns in its embedding space, even in its smallest model. Significantly, we demonstrate that these embeddings can be interpreted using a novel visualization pipeline built using explainable AI techniques.more » « less
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null (Ed.)Abstract Background The Aedes aegypti mosquito is a threat to human health across the globe. The A. aegypti genome was recently re-sequenced and re-assembled. Due to a combination of long-read PacBio and Hi-C sequencing, the AaegL5 assembly is chromosome complete and significantly improves the assembly in key areas such as the M/m sex-determining locus. Release of the updated genome assembly has precipitated the need to reprocess historical functional genomic data sets, including cis -regulatory element (CRE) maps that had previously been generated for A. aegypti. Results We re-processed and re-analyzed the A. aegypti whole embryo FAIRE seq data to create an updated embryonic CRE map for the AaegL5 genome. We validated that the new CRE map recapitulates key features of the original AaegL3 CRE map. Further, we built on the improved assembly in the M/m locus to analyze overlaps of open chromatin regions with genes. To support the validation, we created a new method (PeakMatcher) for matching peaks from the same experimental data set across genome assemblies. Conclusion Use of PeakMatcher software, which is available publicly under an open-source license, facilitated the release of an updated and validated CRE map, which is available through the NIH GEO. These findings demonstrate that PeakMatcher software will be a useful resource for validation and transferring of previous annotations to updated genome assemblies.more » « less
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Background Large (>1 Mb), polymorphic inversions have substantial impacts on population structure and maintenance of genotypes. These large inversions can be detected from single nucleotide polymorphism (SNP) data using unsupervised learning techniques like PCA. Construction and analysis of a feature matrix from millions of SNPs requires large amount of memory and limits the sizes of data sets that can be analyzed. Methods We propose using feature hashing construct a feature matrix from a VCF file of SNPs for reducing memory usage. The matrix is constructed in a streaming fashion such that the entire VCF file is never loaded into memory at one time. Results When evaluated on Anopheles mosquito and Drosophila fly data sets, our approach reduced memory usage by 97% with minimal reductions in accuracy for inversion detection and localization tasks. Conclusion With these changes, inversions in larger data sets can be analyzed easily and efficiently on common laptop and desktop computers. Our method is publicly available through our open-source inversion analysis software, Asaph.more » « less
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Workflow management systems are widely used to express and execute highly parallel applications. For dataintensive workflows, storage can be the constraining resource: the number of tasks running at once must be artificially limited to not overflow the space available in the filesystem. It is all too easy for a user to dispatch a workflow which consumes all available storage and disrupts all system users. To address these issues, we present a three-tiered approach to workflow storage management: (1) A static analysis algorithm which analyzes the storage needs of a workflow before execution, giving a realistic prediction of success or failure. (2) An online storage management algorithm which accounts for the storage needed by future tasks to avoid deadlock at runtime. (3) A task containment system which limits storage consumption of individual tasks, enabling the strong guarantees of the static analysis and dynamic management algorithms. We demonstrate the application of these techniques on three complex workflows.more » « less
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Abstract BackgroundThe stable fly,Stomoxys calcitrans, is a major blood-feeding pest of livestock that has near worldwide distribution, causing an annual cost of over $2 billion for control and product loss in the USA alone. Control of these flies has been limited to increased sanitary management practices and insecticide application for suppressing larval stages. Few genetic and molecular resources are available to help in developing novel methods for controlling stable flies. ResultsThis study examines stable fly biology by utilizing a combination of high-quality genome sequencing and RNA-Seq analyses targeting multiple developmental stages and tissues. In conjunction, 1600 genes were manually curated to characterize genetic features related to stable fly reproduction, vector host interactions, host-microbe dynamics, and putative targets for control. Most notable was characterization of genes associated with reproduction and identification of expanded gene families with functional associations to vision, chemosensation, immunity, and metabolic detoxification pathways. ConclusionsThe combined sequencing, assembly, and curation of the male stable fly genome followed by RNA-Seq and downstream analyses provide insights necessary to understand the biology of this important pest. These resources and new data will provide the groundwork for expanding the tools available to control stable fly infestations. The close relationship ofStomoxysto other blood-feeding (horn flies andGlossina) and non-blood-feeding flies (house flies, medflies,Drosophila) will facilitate understanding of the evolutionary processes associated with development of blood feeding among the Cyclorrhapha.more » « less
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