Matching phenotypes to whole genomes: Lessons learned from four iterations of the personal genome project community challenges.

The advent of next-generation sequencing has dramatically decreased the cost for whole-genome sequencing and increased the viability for its application in research and clinical care. The Personal Genome Project (PGP) provides unrestricted access to genomes of individuals and their associated phenotypes. This resource enabled the Critical Assessment of Genome Interpretation (CAGI) to create a community challenge to assess the bioinformatics community's ability to predict traits from whole genomes. In the CAGI PGP challenge, researchers were asked to predict whether an individual had a particular trait or profile based on their whole genome. Several approaches were used to assess submissions, including ROC AUC (area under receiver operating characteristic curve), probability rankings, the number of correct predictions, and statistical significance simulations. Overall, we found that prediction of individual traits is difficult, relying on a strong knowledge of trait frequency within the general population, whereas matching genomes to trait profiles relies heavily upon a small number of common traits including ancestry, blood type, and eye color. When a rare genetic disorder is present, profiles can be matched when one or more pathogenic variants are identified. Prediction accuracy has improved substantially over the last 6 years due to improved methodology and a better understanding of features.

Toward an open access genomics database of South Africans: ethical considerations.

Genomics research holds the potential to improve healthcare. Yet, a very low percentage of the genomic data used in genomics research internationally relates to persons of African origin. Establishing a large-scale, open access genomics database of South Africans may contribute to solving this problem. However, this raises various ethics concerns, including privacy expectations and informed consent. The concept of open consent offers a potential solution to these concerns by (a) being explicit about the research participant's data being in the public domain and the associated privacy risks, and (b) setting a higher-than-usual benchmark for informed consent by making use of the objective assessment of prospective research participants' understanding. Furthermore, in the South African context-where local culture is infused with Ubuntu and its relational view of personhood-community engagement is vital for establishing and maintaining an open access genomics database of South Africans. The South African National Health Research Ethics Council is called upon to provide guidelines for genomics researchers-based on open consent and community engagement-on how to plan and implement open access genomics projects.

GenomeChronicler: The Personal Genome Project UK Genomic Report Generator Pipeline.

In recent years, there has been a significant increase in whole genome sequencing data of individual genomes produced by research projects as well as direct to consumer service providers. While many of these sources provide their users with an interpretation of the data, there is a lack of free, open tools for generating reports exploring the data in an easy to understand manner. GenomeChronicler was developed as part of the Personal Genome Project UK (PGP-UK) to address this need. PGP-UK provides genomic, transcriptomic, epigenomic and self-reported phenotypic data under an open-access model with full ethical approval. As a result, the reports generated by GenomeChronicler are intended for research purposes only and include information relating to potentially beneficial and potentially harmful variants, but without clinical curation. GenomeChronicler can be used with data from whole genome or whole exome sequencing, producing a genome report containing information on variant statistics, ancestry and known associated phenotypic traits. Example reports are available from the PGP-UK data page (personalgenomes.org.uk/data). The objective of this method is to leverage existing resources to find known phenotypes associated with the genotypes detected in each sample. The provided trait data is based primarily upon information available in SNPedia, but also collates data from ClinVar, GETevidence, and gnomAD to provide additional details on potential health implications, presence of genotype in other PGP participants and population frequency of each genotype. The analysis can be run in a self-contained environment without requiring internet access, making it a good choice for cases where privacy is essential or desired: any third party project can embed GenomeChronicler within their off-line safe-haven environments. GenomeChronicler can be run for one sample at a time, or in parallel making use of the Nextflow workflow manager. The source code is available from GitHub (https://github.com/PGP-UK/GenomeChronicler), container recipes are available for Docker and Singularity, as well as a pre-built container from SingularityHub (https://singularity-hub.org/collections/3664) enabling easy deployment in a variety of settings. Users without access to computational resources to run GenomeChronicler can access the software from the Lifebit CloudOS platform (https://lifebit.ai/cloudos) enabling the production of reports and variant calls from raw sequencing data in a scalable fashion.

Jordanians' Perspectives On Open Consent In Biomedical Research.

INTRODUCTION: The informed consent process is an integral step in biomedical research. However, the emergence of biobanks and the need for open consent (also called "broad" or "blanket" consent) create challenges to this process. AIMS AND METHODOLOGY: A survey was used to examine Jordanians' perspectives on open consent and reuse of stored samples in future research. RESULTS: The majority of participants had positive perceptions of informed consent and its importance. In addition, they appreciated the challenges that are associated with multiple uses of their biospecimens. About 55% agreed to provide open consent for reuse of their donated biospecimens. Participants (75-80%) also agreed that issues such as the possibility of sharing samples with international research centers, storage duration, and use of biospecimens after their death should be clarified as part of open consent. The inconvenience of the re-contact process, trust in the research team, and the importance of biobanks were all associated with participants' willingness to provide open consent (P<0.05). On the other hand, privacy and confidentiality, doubt about future use of samples, unknown storage period, and the possibility of cross-border sample sharing were significantly associated with participants' reluctance to provide open consent. CONCLUSION: The majority of Jordanians accept the idea of open consent. Clarification of issues such as international sample sharing, duration of storage, domains of intended research, confidentiality, and privacy can provide more support for the use of open consent.

Personal Genome Project UK (PGP-UK): a research and citizen science hybrid project in support of personalized medicine.

BACKGROUND: Molecular analyses such as whole-genome sequencing have become routine and are expected to be transformational for future healthcare and lifestyle decisions. Population-wide implementation of such analyses is, however, not without challenges, and multiple studies are ongoing to identify what these are and explore how they can be addressed. METHODS: Defined as a research project, the Personal Genome Project UK (PGP-UK) is part of the global PGP network and focuses on open data sharing and citizen science to advance and accelerate personalized genomics and medicine. RESULTS: Here we report our findings on using an open consent recruitment protocol, active participant involvement, open access release of personal genome, methylome and transcriptome data and associated analyses, including 47 new variants predicted to affect gene function and innovative reports based on the analysis of genetic and epigenetic variants. For this pilot study, we recruited 10 participants willing to actively engage as citizen scientists with the project. In addition, we introduce Genome Donation as a novel mechanism for openly sharing previously restricted data and discuss the first three donations received. Lastly, we present GenoME, a free, open-source educational app suitable for the lay public to allow exploration of personal genomes. CONCLUSIONS: Our findings demonstrate that citizen science-based approaches like PGP-UK have an important role to play in the public awareness, acceptance and implementation of genomics and personalized medicine.