Adam Faulconbridge

Common genetic variation drives molecular heterogeneity in human iPSCs

Technology utilizing human induced pluripotent stem cells (iPS cells) has enormous potential to provide improved cellular models of human disease. However, variable genetic and phenotypic characterization of many existing iPS cell lines limits their potential use for research and therapy. Here we describe the systematic generation, genotyping and phenotyping of 711 iPS cell lines derived from 301 healthy individuals by the Human Induced Pluripotent Stem Cells Initiative. Our study outlines the major sources of genetic and phenotypic variation in iPS cells and establishes their suitability as models of complex human traits and cancer. Through genome-wide profiling we find that 5–46% of the variation in different iPS cell phenotypes, including differentiation capacity and cellular morphology, arises from differences between individuals. Additionally, we assess the phenotypic consequences of genomic copy-number alterations that are repeatedly observed in iPS cells. In addition, we present a comprehensive map of common regulatory variants affecting the transcriptome of human pluripotent cells.

The BioSample Database (BioSD) at the European Bioinformatics Institute

The BioSample Database (http://www.ebi.ac.uk/biosamples) is a new database at EBI that stores information about biological samples used in molecular experiments, such as sequencing, gene expression or proteomics. The goals of the BioSample Database include: (i) recording and linking of sample information consistently within EBI databases such as ENA, ArrayExpress and PRIDE; (ii) minimizing data entry efforts for EBI database submitters by enabling submitting sample descriptions once and referencing them later in data submissions to assay databases and (iii) supporting cross database queries by sample characteristics. Each sample in the database is assigned an accession number. The database includes a growing set of reference samples, such as cell lines, which are repeatedly used in experiments and can be easily referenced from any database by their accession numbers. Accession numbers for the reference samples will be exchanged with a similar database at NCBI. The samples in the database can be queried by their attributes, such as sample types, disease names or sample providers. A simple tab-delimited format facilitates submissions of sample information to the database, initially via email to biosamples@ebi.ac.uk

Updates to BioSamples database at European Bioinformatics Institute

The BioSamples database at the EBI (http://www.ebi.ac.uk/biosamples) provides an integration point for BioSamples information between technology specific databases at the EBI, projects such as ENCODE and reference collections such as cell lines. The database delivers a unified query interface and API to query sample information across EBI’s databases and provides links back to assay databases. Sample groups are used to manage related samples, e.g. those from an experimental submission, or a single reference collection. Infrastructural improvements include a new user interface with ontological and key word queries, a new query API, a new data submission API, complete RDF data download and a supporting SPARQL endpoint, accessioning at the point of submission to the European Nucleotide Archive and European Genotype Phenotype Archives and improved query response times.

The human-induced pluripotent stem cell initiative-data resources for cellular genetics.

The Human Induced Pluripotent Stem Cell Initiative (HipSci) isf establishing a large catalogue of human iPSC lines, arguably the most well characterized collection to date. The HipSci portal enables researchers to choose the right cell line for their experiment, and makes HipScis rich catalogue of assay data easy to discover and reuse. Each cell line has genomic, transcriptomic, proteomic and cellular phenotyping data. Data are deposited in the appropriate EMBL-EBI archives, including the European Nucleotide Archive (ENA), European Genome-phenome Archive (EGA), ArrayExpress and PRoteomics IDEntifications (PRIDE) databases. The project will make 500 cell lines from healthy individuals, and from 150 patients with rare genetic diseases; these will be available through the European Collection of Authenticated Cell Cultures (ECACC). As of August 2016, 238 cell lines are available for purchase. Project data is presented through the HipSci data portal (http://www.hipsci.org/lines) and is downloadable from the associated FTP site (ftp://ftp.hipsci.ebi.ac.uk/vol1/ftp). The data portal presents a summary matrix of the HipSci cell lines, showing available data types. Each line has its own page containing descriptive metadata, quality information, and links to archived assay data. Analysis results are also available in a Track Hub, allowing visualization in the context of public genomic annotations (http://www.hipsci.org/data/trackhubs).

A Standard Nomenclature for Referencing and Authentication of Pluripotent Stem Cells

Unambiguous cell line authentication is essential to avoid loss of association between data and cells. The risk for loss of references increases with the rapidity that new human pluripotent stem cell (hPSC) lines are generated, exchanged, and implemented. Ideally, a single name should be used as a generally applied reference for each cell line to access and unify cell-related information across publications, cell banks, cell registries, and databases and to ensure scientific reproducibility. We discuss the needs and requirements for such a unique identifier and implement a standard nomenclature for hPSCs, which can be automatically generated and registered by the human pluripotent stem cell registry (hPSCreg). To avoid ambiguities in PSC-line referencing, we strongly urge publishers to demand registration and use of the standard name when publishing research based on hPSC lines.

Corrigendum: Common genetic variation drives molecular heterogeneity in human iPSCs

This corrects the article DOI: 10.1038/nature22403.