Building a collaborative cloud platform to accelerate heart, lung, blood, and sleep research.

Research increasingly relies on interrogating large-scale data resources. The NIH National Heart, Lung, and Blood Institute developed the NHLBI BioData CatalystⓇ (BDC), a community-driven ecosystem where researchers, including bench and clinical scientists, statisticians, and algorithm developers, find, access, share, store, and compute on large-scale datasets. This ecosystem provides secure, cloud-based workspaces, user authentication and authorization, search, tools and workflows, applications, and new innovative features to address community needs, including exploratory data analysis, genomic and imaging tools, tools for reproducibility, and improved interoperability with other NIH data science platforms. BDC offers straightforward access to large-scale datasets and computational resources that support precision medicine for heart, lung, blood, and sleep conditions, leveraging separately developed and managed platforms to maximize flexibility based on researcher needs, expertise, and backgrounds. Through the NHLBI BioData Catalyst Fellows Program, BDC facilitates scientific discoveries and technological advances. BDC also facilitated accelerated research on the coronavirus disease-2019 (COVID-19) pandemic.

Mutations in coral soma and sperm imply lifelong stem cell renewal and cell lineage selection.

In many animals, the germline differentiates early in embryogenesis, so only mutations that accumulate in germ cells are inherited by offspring. Exceptions to this developmental process may indicate other mechanisms have evolved to limit the effects of deleterious mutation accumulation. Stony corals are animals that can live for hundreds of years and have been thought to produce gametes from somatic tissue. To clarify conflicting evidence about germline-soma distinction in corals, we sequenced high coverage, full genomes with technical replicates for parent coral branches and their sperm pools. We identified post-embryonic single nucleotide variants (SNVs) unique to each parent branch, then checked if each SNV was shared by the respective sperm pool. Twenty-six per cent of post-embryonic SNVs were shared by the sperm and 74% were not. We also identified germline SNVs, those that were present in the sperm but not in the parent. These data suggest that self-renewing stem cells differentiate into germ and soma throughout the adult life of the colony, with SNV rates and patterns differing markedly in stem, soma and germ lineages. In addition to informing the evolution of germlines in metazoans, these insights inform how corals may generate adaptive diversity necessary in the face of global climate change.

Genomic analysis of distinct bleaching tolerances among cryptic coral species.

Reef-building coral species are experiencing an unprecedented decline owing to increasing frequency and intensity of marine heatwaves and associated bleaching-induced mortality. Closely related species from the Acropora hyacinthus species complex differ in heat tolerance and in their association with heat-tolerant symbionts. We used low-coverage full genome sequencing of 114 colonies monitored across the 2015 bleaching event in American Samoa to determine the genetic differences among four cryptic species (termed HA, HC, HD and HE) that have diverged in these species traits. Cryptic species differed strongly at thousands of single nucleotide polymorphisms across the genome which are enriched for amino acid changes in the bleaching-resistant species HE. In addition, HE also showed two particularly divergent regions with strong signals of differentiation. One approximately 220 kb locus, HES1, contained the majority of fixed differences in HE. A second locus, HES2, was fixed in HE but polymorphic in the other cryptic species. Surprisingly, non-HE individuals with HE-like haplotypes at HES2 were more likely to bleach. At both loci, HE showed particular sequence similarity to a congener, Acropora millepora. Overall, resilience to bleaching during the third global bleaching event was strongly structured by host cryptic species, buoyed by differences in symbiont associations between these species.

The Dockstore: enhancing a community platform for sharing reproducible and accessible computational protocols.

Dockstore (https://dockstore.org/) is an open source platform for publishing, sharing, and finding bioinformatics tools and workflows. The platform has facilitated large-scale biomedical research collaborations by using cloud technologies to increase the Findability, Accessibility, Interoperability and Reusability (FAIR) of computational resources, thereby promoting the reproducibility of complex bioinformatics analyses. Dockstore supports a variety of source repositories, analysis frameworks, and language technologies to provide a seamless publishing platform for authors to create a centralized catalogue of scientific software. The ready-to-use packaging of hundreds of tools and workflows, combined with the implementation of interoperability standards, enables users to launch analyses across multiple environments. Dockstore is widely used, more than twenty-five high-profile organizations share analysis collections through the platform in a variety of workflow languages, including the Broad Institute's GATK best practice and COVID-19 workflows (WDL), nf-core workflows (Nextflow), the Intergalactic Workflow Commission tools (Galaxy), and workflows from Seven Bridges (CWL) to highlight just a few. Here we describe the improvements made over the last four years, including the expansion of system integrations supporting authors, the addition of collaboration features and analysis platform integrations supporting users, and other enhancements that improve the overall scientific reproducibility of Dockstore content.

Ocean acidification causes variable trait-shifts in a coral species.

High pCO2 habitats and their populations provide an unparalleled opportunity to assess how species may survive under future ocean acidification conditions, and help to reveal the traits that confer tolerance. Here we utilize a unique CO2 vent system to study the effects of exposure to elevated pCO2 on trait-shifts observed throughout natural populations of Astroides calycularis, an azooxanthellate scleractinian coral endemic to the Mediterranean. Unexpected shifts in skeletal and growth patterns were found. Colonies shifted to a skeletal phenotype characterized by encrusting morphology, smaller size, reduced coenosarc tissue, fewer polyps, and less porous and denser skeletons at low pH. Interestingly, while individual polyps calcified more and extended faster at low pH, whole colonies found at low pH site calcified and extended their skeleton at the same rate as did those at ambient pH sites. Transcriptomic data revealed strong genetic differentiation among local populations of this warm water species whose distribution range is currently expanding northward. We found excess differentiation in the CO2 vent population for genes central to calcification, including genes for calcium management (calmodulin, calcium-binding proteins), pH regulation (V-type proton ATPase), and inorganic carbon regulation (carbonic anhydrase). Combined, our results demonstrate how coral populations can persist in high pCO2 environments, making this system a powerful candidate for investigating acclimatization and local adaptation of organisms to global environmental change.

Early Transcriptional Responses during Heat Stress in the Coral Acropora hyacinthus.

Corals respond to heat pulses that cause bleaching with massive transcriptional change, but the immediate responses to stress that lead up to these shifts have never been detailed. Understanding these early signals could be important for identifying the regulatory mechanisms responsible for bleaching and how these mechanisms vary between more and less resilient corals. Using RNA sequencing (RNAseq) and sampling every 30 minutes during a short-term heat shock, we found that components of the transcriptome were significantly upregulated within 90 min and after a temperature increase of +2 °C. The developmental transcription factor, Krüppel-like factor 7, was highly expressed within 60 min, and stress-related transcription factors such as Elk-3 were highly expressed starting at 240 min. The sets of genes enriched for early transcriptional response to heat stress included heat shock proteins, small GTPases, and proteasome genes. Retrovirus-related Pol polyproteins from transposons were significantly expressed throughout the whole experiment. Lastly, we propose a model for early transcriptional regulation of protein degradation and cell adhesion response that may ultimately lead to the bleaching and stress response.

Investigating the widespread introduction of a tropical marine fouling species.

Little is known about the number and rate of introductions into terrestrial and marine tropical regions, and if introduction patterns and processes differ from temperate latitudes. Botryllid ascidians (marine invertebrate chordates) are an interesting group to study such introduction differences because several congeners have established populations across latitudes. While temperate botryllid invasions have been repeatedly highlighted, the global spread of tropical Botrylloides nigrum (Herdman, 1886) has been largely ignored. We sampled B. nigrum from 16 worldwide warm water locations, including around the Panama Canal, one of the largest shipping hubs in the world and a possible introduction corridor. Using mitochondrial (COI) and nuclear (ANT) markers, we discovered a single species with low genetic divergence and diversity that has established in the Atlantic, Pacific, Indo-Pacific, and Mediterranean Oceans. The Atlantic Ocean contained the highest diversity and multilocus theta estimates and may be a source for introductions to other regions. A high frequency of one mitochondrial haplotype was detected in Pacific populations that may represent a recent introduction in this region. In comparison to temperate relatives, B. nigrum displayed lower (but similar to temperate Botrylloides violaceus) genetic divergence and diversity at both loci that may represent a more recent global spread or differences in introduction pressures in tropical regions. Additionally, chimeras (genetically distinct individuals sharing a single body) were detected in three populations by the mitochondrial locus and validated using cloning, and these individuals contained new haplotype diversity not detected in any other colonies.