Remote visualization of large-scale genomic alignments for collaborative clinical research and diagnosis of rare diseases.

The Solve-RD project objectives include solving undiagnosed rare diseases (RD) through collaborative research on shared genome-phenome datasets. The RD-Connect Genome-Phenome Analysis Platform (GPAP), for data collation and analysis, and the European Genome-Phenome Archive (EGA), for file storage, are two key components of the Solve-RD infrastructure. Clinical researchers can identify candidate genetic variants within the RD-Connect GPAP and, thanks to the developments presented here as part of joint ELIXIR activities, are able to remotely visualize the corresponding alignments stored at the EGA. The Global Alliance for Genomics and Health (GA4GH) htsget streaming application programming interface (API) is used to retrieve alignment slices, which are rendered by an integrated genome viewer (IGV) instance embedded in the GPAP. As a result, it is no longer necessary for over 11,000 datasets to download large alignment files to visualize them locally. This work highlights the advantages, from both the user and infrastructure perspectives, of implementing interoperability standards for establishing federated genomics data networks.

Tackling the translational challenges of multi-omics research in the realm of European personalised medicine: A workshop report.

Personalised medicine (PM) presents a great opportunity to improve the future of individualised healthcare. Recent advances in -omics technologies have led to unprecedented efforts characterising the biology and molecular mechanisms that underlie the development and progression of a wide array of complex human diseases, supporting further development of PM. This article reflects the outcome of the 2021 EATRIS-Plus Multi-omics Stakeholder Group workshop organised to 1) outline a global overview of common promises and challenges that key European stakeholders are facing in the field of multi-omics research, 2) assess the potential of new technologies, such as artificial intelligence (AI), and 3) establish an initial dialogue between key initiatives in this space. Our focus is on the alignment of agendas of European initiatives in multi-omics research and the centrality of patients in designing solutions that have the potential to advance PM in long-term healthcare strategies.

The Dasya baillouviana and D. cryptica complexes (Delesseriaceae, Rhodophyta) in Bermuda with three additional new species from the archipelago.

Continuing molecular studies of the red algal genus Dasya collected off the coast of Bermuda have revealed two new species in the developing D. cryptica species complex-one from each the euphotic and mesophotic zones, D. orae sp. nov. and D. bathypelagica sp. nov., respectively. Furthermore, what was known as D. baillouviana in Bermuda is shown to represent D. hibernae sp. nov., a sibling of D. pedicellata from New England and New York, USA. Despite morphological similarities to the recently described shallow subtidal species from the islands, D. cryptica, molecular sequencing and morphological comparisons demonstrated that a new set of inshore specimens represented D. orae. The larger, new deep-water species, D. bathypelagica, was genetically compared with recent Bermuda collections of D. baillouviana and others worldwide morphologically falling under this epithet and represented a new species also grouping in the D. cryptica complex. The specimens of D. hibernae from Bermuda were shown to be genetically distinct from specimens of D. pedicellata from southern New England and New York. Molecular analyses necessitated the resurrection of D. pedicellata and uncovered undescribed species in the D. baillouviana complex in the western Atlantic. Based upon genetic evidence provided here, the generitype of Rhodoptilum nested among species in the D. baillouviana complex including the generitype. This finding required the synonymy of the genus Rhodoptilum with Dasya and allowed for the reinstatement of D. plumosa. Furthermore, Dasya collinsiana resolved in the lineage including a closely related species to the generitype of Dasysiphonia, necessitating the transfer of this Bermudian species and others worldwide from the genus Dasya to Dasysiphonia.

Beacon v2 and Beacon networks: A "lingua franca" for federated data discovery in biomedical genomics, and beyond.

Beacon is a basic data discovery protocol issued by the Global Alliance for Genomics and Health (GA4GH). The main goal addressed by version 1 of the Beacon protocol was to test the feasibility of broadly sharing human genomic data, through providing simple "yes" or "no" responses to queries about the presence of a given variant in datasets hosted by Beacon providers. The popularity of this concept has fostered the design of a version 2, that better serves real-world requirements and addresses the needs of clinical genomics research and healthcare, as assessed by several contributing projects and organizations. Particularly, rare disease genetics and cancer research will benefit from new case level and genomic variant level requests and the enabling of richer phenotype and clinical queries as well as support for fuzzy searches. Beacon is designed as a "lingua franca" to bridge data collections hosted in software solutions with different and rich interfaces. Beacon version 2 works alongside popular standards like Phenopackets, OMOP, or FHIR, allowing implementing consortia to return matches in beacon responses and provide a handover to their preferred data exchange format. The protocol is being explored by other research domains and is being tested in several international projects.

The European Variation Archive: a FAIR resource of genomic variation for all species.

The European Variation Archive (EVA; https://www.ebi.ac.uk/eva/) is a resource for sharing all types of genetic variation data (SNPs, indels, and structural variants) for all species. The EVA was created in 2014 to provide FAIR access to genetic variation data and has since grown to be a primary resource for genomic variants hosting >3 billion records. The EVA and dbSNP have established a compatible global system to assign unique identifiers to all submitted genetic variants. The EVA is active within the Global Alliance of Genomics and Health (GA4GH), maintaining, contributing and implementing standards such as VCF, Refget and Variant Representation Specification (VRS). In this article, we describe the submission and permanent accessioning services along with the different ways the data can be retrieved by the scientific community.

The Data Use Ontology to streamline responsible access to human biomedical datasets.

Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset's allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers' discovery and access of relevant datasets. DUO annotations increase the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.

Unique biodiversity in Arctic marine forests is shaped by diverse recolonization pathways and far northern glacial refugia.

The Arctic is experiencing a rapid shift toward warmer regimes, calling for a need to understand levels of biodiversity and ecosystem responses to climate cycles. This study presents genetic data for 109 Arctic marine forest species (seaweeds), which revealed contiguous populations extending from the Bering Sea to the northwest Atlantic, with high levels of genetic diversity in the east Canadian Arctic. One-fifth of the species sampled appeared restricted to Arctic waters. Further supported by hindcasted species distributions during the Last Glacial Maximum, we hypothesize that Arctic coastal systems were recolonized from many geographically disparate refugia leading to enriched diversity levels in the east Canadian Arctic, with important contributions stemming from northerly refugia likely centered along southern Greenland. Our results suggest Arctic marine biomes persisted through cycles of glaciation, leading to unique assemblages in polar waters, rather than being entirely derived from southerly (temperate) areas following glaciation. As such, Arctic marine species are potentially born from selective pressures during Cenozoic global cooling and eventual ice conditions beginning in the Pleistocene. Arctic endemic diversity was likely additionally driven by repeated isolations into globally disparate refugia during glaciation. This study highlights the need to take stock of unique Arctic marine biodiversity. Amplification of warming and loss of perennial ice cover are set to dramatically alter available Arctic coastal habitat, with the potential loss of diversity and decline in ecosystem resilience.

The ELIXIR Human Copy Number Variations Community: building bioinformatics infrastructure for research.

Copy number variations (CNVs) are major causative contributors both in the genesis of genetic diseases and human neoplasias. While "High-Throughput" sequencing technologies are increasingly becoming the primary choice for genomic screening analysis, their ability to efficiently detect CNVs is still heterogeneous and remains to be developed. The aim of this white paper is to provide a guiding framework for the future contributions of ELIXIR's recently established human CNV Community, with implications beyond human disease diagnostics and population genomics. This white paper is the direct result of a strategy meeting that took place in September 2018 in Hinxton (UK) and involved representatives of 11 ELIXIR Nodes. The meeting led to the definition of priority objectives and tasks, to address a wide range of CNV-related challenges ranging from detection and interpretation to sharing and training. Here, we provide suggestions on how to align these tasks within the ELIXIR Platforms strategy, and on how to frame the activities of this new ELIXIR Community in the international context.

An intrinsically disordered proteins community for ELIXIR.

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are now recognised as major determinants in cellular regulation. This white paper presents a roadmap for future e-infrastructure developments in the field of IDP research within the ELIXIR framework. The goal of these developments is to drive the creation of high-quality tools and resources to support the identification, analysis and functional characterisation of IDPs. The roadmap is the result of a workshop titled "An intrinsically disordered protein user community proposal for ELIXIR" held at the University of Padua. The workshop, and further consultation with the members of the wider IDP community, identified the key priority areas for the roadmap including the development of standards for data annotation, storage and dissemination; integration of IDP data into the ELIXIR Core Data Resources; and the creation of benchmarking criteria for IDP-related software. Here, we discuss these areas of priority, how they can be implemented in cooperation with the ELIXIR platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for an IDP Community in ELIXIR and is an appeal to identify and involve new stakeholders.

Author Correction: Leveraging European infrastructures to access 1 million human genomes by 2022.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Leveraging European infrastructures to access 1 million human genomes by 2022.

Human genomics is undergoing a step change from being a predominantly research-driven activity to one driven through health care as many countries in Europe now have nascent precision medicine programmes. To maximize the value of the genomic data generated, these data will need to be shared between institutions and across countries. In recognition of this challenge, 21 European countries recently signed a declaration to transnationally share data on at least 1 million human genomes by 2022. In this Roadmap, we identify the challenges of data sharing across borders and demonstrate that European research infrastructures are well-positioned to support the rapid implementation of widespread genomic data access.

Publisher Correction: Federated discovery and sharing of genomic data using Beacons.

In the version of this article initially published, Lena Dolman's second affiliation was given as Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK. The correct second affiliation is Ontario Institute for Cancer Research, Toronto, Ontario, Canada. The error has been corrected in the HTML and PDF versions of the article.

Collections from the mesophytic zone off Bermuda reveal three species of Kallymeniaceae (Gigartinales, Rhodophyta) in genera with transoceanic distributions.

A molecular survey of red algae collected by technical divers and submersibles from 90 m in the mesophotic zone off the coast of Bermuda revealed three species assignable to the Kallymeniaceae. Two of the species are representative of recently described genera centered in the western Pacific in Australia and New Zealand, Austrokallymenia and Psaromenia and the third from the Mediterranean Sea and the eastern Atlantic, Nothokallymenia. A phylogenetic analysis of concatenated mitochondrial (COI-5P) and chloroplast (rbcL) genes, as well as morphological characteristics, revealed that two are shown to be new species with distant closest relatives (N. erosa and Psaromenia septentrionalis), while the third represents a deep water western Atlantic species now moved to an Australasian genus (A. westii).

Glacial vicariance drives phylogeographic diversification in the amphi-boreal kelp Saccharina latissima.

Glacial vicariance is regarded as one of the most prevalent drivers of phylogeographic structure and speciation among high-latitude organisms, but direct links between ice advances and range fragmentation have been more difficult to establish in marine than in terrestrial systems. Here we investigate the evolution of largely disjunct (and potentially reproductively isolated) phylogeographic lineages within the amphi-boreal kelp Saccharina latissima s. l. Using molecular data (COI, microsatellites) we confirm that S. latissima comprises also the NE Pacific S. cichorioides complex and is composed of divergent lineages with limited range overlap and genetic admixture. Only a few genetic hybrids were detected throughout a Canadian Arctic/NW Greenland contact zone. The degree of genetic differentiation and sympatric isolation of phylogroups suggest that S. latissima s. l. represents a complex of incipient species. Phylogroup distributions compared with paleo-environmental reconstructions of the cryosphere further suggest that diversification within S. latissima results from chronic glacial isolation in disjunct persistence areas intercalated with ephemeral interglacial poleward expansions and admixture at high-latitude (Arctic) contact zones. This study thus supports a role for glaciations not just in redistributing pre-existing marine lineages but also as a speciation pump across multi-glacial cycles for marine organisms otherwise exhibiting cosmopolite amphi-boreal distributions.

Ottia meiospora (Ottiaceae, Rhodophyta), a new genus and family endophytic within the thallus of Nothocladus (Batrachospermales, Rhodophyta).

A new genus, Ottia, and family, Ottiaceae, are proposed within the Acrochaetiales to accommodate the uniseriate red algal endophyte of batrachspermalean taxa previously named Balbiania meiospora. Prior to this study, Balbiania investiens was transferred to its own family and order (Balbianiales) based on comparative DNA sequence data and a distinctive reproductive morphology. However, the second species described in this genus, B. meiospora, continued to be treated as a species of Audouinella (A. meiospora) pending further investigation. Phylogenetic analyses of sequence data confirmed only a distant relationship between the two endophytes, and a closer alliance of B. meiospora to Acrochaetiales. The data also showed that Ottia meiospora was the deepest diverging lineage in the Acrochaetiales, sister to all of the currently recognized genera and families. In this study, we review the classification of what we now call O. meiospora - reported from Australia, New Zealand and Brazil - based on sequence and morphological data. Morphological observations provided little clarity around the reproductive morphology or the life cycle of this endophyte of Nothocladus s. lat. found commonly in mainland Australia but, to date, less so in New Zealand.

Phylogenetic analyses of transcriptome data resolve familial assignments for genera of the red-algal Acrochaetiales-Palmariales Complex (Nemaliophycidae).

Phylogenetic analyses of transcriptome data for representatives of the red algal Acrochaetiales-Palmariales Complex provided robust support for the assignment of genera to the constituent families. In the Acrochaetiales, the genera Acrochaetium, Grania, and an unnamed genus-level lineage (Acrochaetiac sp._1Aus) were assigned to the Acrochaetiaceae, while Audouinella is placed in a resurrected Audouinellaceae and Rhodochorton and Rhododrewia constitute the resurrected Rhodochortonaceae. For the Palmariales, transcriptome data solidly support the inclusion of Camontagnea and Rhodothamniella in the Rhodothamniellaceae, Meiodiscus and Rubrointrusa in the Meiodiscaceae, Rhodonematella and Rhodophysema in the Rhodophysemataceae, while Devaleraea and Palmaria remained in the Palmariaceae. These analyses, however, questioned the monophyly of Palmaria, which prompted a second round of analyses using eight common red algal phylogenetic markers and including a broader sampling of red algal genera in our analyses. These results supported transfer of Palmaria callophylloides and P. mollis to the genus Devaleraea necessitating new combinations, and further added the genus Halosaccion to the Palmariaceae and the genera Kallymenicola and Rhodophysemopsis to the Meiodiscaceae. Finally, DNA barcode (mitochondrial COI-5P) and ITS data were explored and supported the continued recognition of Palmaria palmata as a single species in the North Atlantic.

PCR fishing for red endophytes in British Columbia Kallymeniaceae (Gigartinales, Florideophyceae) uncovers the species-rich Kallymenicola gen. nov. (Palmariales, Nemaliophycidae).

Unexpected contaminants uncovered during routine COI-5P DNA barcoding of British Columbia Kallymeniaceae indicated the presence of a novel lineage allied to the family Meiodiscaceae, Palmariales. Available rbcL data for species of this family were used to design specific primers to screen for the presence of the meiodiscacean species in 534 kallymeniacean specimens primarily from British Columbia, Canada. Ultimately, 43 positive PCR products representing six diverse genetic groups from nine host species were uncovered; three are described here in the new genus Kallymenicola gen. nov., viz., K. invisiblis sp. nov., K penetrans sp. nov., and K superficialis sp. nov. Although genetic groups loosely displayed evidence of host specificity and cospeciation, examples of host switching with interesting biogeographical patterns were also documented.

Open Targets: a platform for therapeutic target identification and validation.

We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org.