Ten simple rules for responsible big data research Zook, Matthew; Barocas, Solon; Boyd, Danah ...
PLOS computational biology/PLoS computational biology,
03/2017, Letnik:
13, Številka:
3
Journal Article
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About the Authors: Matthew Zook * E-mail: zook@uky.edu Affiliation: Department of Geography, University of Kentucky, Lexington, Kentucky, United States of America Solon Barocas Affiliation: Microsoft ...Research, New York, New York, United States of America danah boyd Affiliations Microsoft Research, New York, New York, United States of America, Data & Society, New York, New York, United States of America Kate Crawford Affiliations Microsoft Research, New York, New York, United States of America, Information Law Institute, New York University, New York, New York, United States of America Emily Keller Affiliation: Data & Society, New York, New York, United States of America ORCID http://orcid.org/0000-0001-9189-0421 Seeta Peña Gangadharan Affiliation: Department of Media and Communications, London School of Economics, London, United Kingdom ORCID http://orcid.org/0000-0002-1955-3874 Alyssa Goodman Affiliation: Harvard-Smithsonian Center for Astrophysics, Harvard University, Cambridge, Massachusetts, United States of America Rachelle Hollander Affiliation: Center for Engineering Ethics and Society, National Academy of Engineering, Washington, DC, United States of America Barbara A. Koenig Affiliation: Institute for Health Aging, University of California-San Francisco, San Francisco, California, United States of America Jacob Metcalf Affiliation: Ethical Resolve, Santa Cruz, California, United States of America ORCID http://orcid.org/0000-0002-2803-6625 Arvind Narayanan Affiliation: Department of Computer Science, Princeton University, Princeton, New Jersey, United States of America Alondra Nelson Affiliation: Department of Sociology, Columbia University, New York, New York, United States of America Frank Pasquale Affiliation: Carey School of Law, University of Maryland, Baltimore, Maryland, United States of AmericaCitation: Zook M, Barocas S, boyd d, Crawford K, Keller E, Gangadharan SP, et al. PLoS Comput...
Have We Asked Too Much of Consent? Koenig, Barbara A.
The Hastings Center report,
July-August 2014, Letnik:
44, Številka:
4
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Paul Appelbaum and colleagues propose four models of informed consent to research that deploys whole genome sequencing and may generate incidental findings. They base their analysis on empirical data ...that suggests that research participants want to be offered incidental findings and on a normative consensus that researchers incur a duty to offer them. Their models will contribute to the heated policy debate about return of incidental findings. But in my view, they do not ask the foundational question, In the context of genome sequencing, how much work can consent be asked to do?
Public health newborn screening (NBS) programs provide population-scale ascertainment of rare, treatable conditions that require urgent intervention. Tandem mass spectrometry (MS/MS) is currently ...used to screen newborns for a panel of rare inborn errors of metabolism (IEMs)
. The NBSeq project evaluated whole-exome sequencing (WES) as an innovative methodology for NBS. We obtained archived residual dried blood spots and data for nearly all IEM cases from the 4.5 million infants born in California between mid-2005 and 2013 and from some infants who screened positive by MS/MS, but were unaffected upon follow-up testing. WES had an overall sensitivity of 88% and specificity of 98.4%, compared to 99.0% and 99.8%, respectively for MS/MS, although effectiveness varied among individual IEMs. Thus, WES alone was insufficiently sensitive or specific to be a primary screen for most NBS IEMs. However, as a secondary test for infants with abnormal MS/MS screens, WES could reduce false-positive results, facilitate timely case resolution and in some instances even suggest more appropriate or specific diagnosis than that initially obtained. This study represents the largest, to date, sequencing effort of an entire population of IEM-affected cases, allowing unbiased assessment of current capabilities of WES as a tool for population screening.
Ethics and Genomic Incidental Findings McGuire, Amy L.; Joffe, Steven; Koenig, Barbara A. ...
Science,
05/2013, Letnik:
340, Številka:
6136
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The American College of Medical Genetics and Genomics (ACMG) recently issued a statement (1) recommending that all laboratories conducting clinical sequencing seek and report pathogenic and expected ...pathogenic mutations for a short list of carefully chosen genes and conditions. The recommendations establish a baseline for reporting clinically relevant incidental findings and articulate ethical principles relevant to their disclosure. The ACMG acknowledged that the list will evolve over time and is developing a mechanism for community input (2). This paper focuses on the ethical framework for the recommendations, rather than on the choice of which genes to include on the list.
Many scientists and doctors hope that affordable genome sequencing will lead to more personalized medical care and improve public health in ways that will benefit children, families, and society more ...broadly. One hope in particular is that all newborns could be sequenced at birth, thereby setting the stage for a lifetime of medical care and self‐directed preventive actions tailored to each child's genome. Indeed, commentators often suggest that universal genome sequencing is inevitable. Such optimism can come with the presumption that discussing the potential limits, cost, and downsides of widespread application of genomic technologies is pointless, excessively pessimistic, or overly cautious. We disagree. Given the pragmatic challenges associated with determining what sequencing data mean for the health of individuals, the economic costs associated with interpreting and acting on such data, and the psychosocial costs of predicting one's own or one's child's future life plans based on uncertain testing results, we think this hope and optimism deserve to be tempered.
In the analysis that follows, we distinguish between two reasons for using sequencing: to diagnose individual infants who have been identified as sick and to screen populations of infants who appear to be healthy. We also distinguish among three contexts in which sequencing for either diagnosis or screening could be deployed: in clinical medicine, in public health programs, and as a direct‐to‐consumer service. Each of these contexts comes with different professional norms, policy considerations, and public expectations. Finally, we distinguish between two main types of genome sequencing: targeted sequencing, where only specific genes are sequenced or analyzed, and whole‐exome or whole‐genome sequencing, where all the DNA or all the coding segments of all genes are sequenced and analyzed.
In a symptomatic newborn, targeted or genome‐wide sequencing can help guide other tests for diagnosis or for specific treatment that is urgently needed. Clinicians use the infant's symptoms (or phenotype) to interrogate the sequencing data. These same complexities and uncertainties, however, limit the usefulness of genome‐wide sequencing as a population screening tool. While we recognize considerable benefit in using targeted sequencing to screen for or detect specific conditions that meet the criteria for inclusion in newborn screening panels, use of genome‐wide sequencing as a sole screening tool for newborns is at best premature. We conclude that sequencing technology can be beneficially used in newborns when that use is nuanced and attentive to context.
A draft human pangenome reference Liao, Wen-Wei; Asri, Mobin; Ebler, Jana ...
Nature,
05/2023, Letnik:
617, Številka:
7960
Journal Article
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Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse ...individuals
. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.
United States-based biorepositories are on the cusp of substantial change in regulatory oversight at the same time that they are increasingly including samples and data from large populations, e.g. ...all patients in healthcare system. It is appropriate to engage stakeholders from these populations in new governance arrangements. We sought to describe community recommendations for biorepository governance and oversight using deliberative community engagement (DCE), a qualitative research method designed to elicit lay perspectives on complex technical issues. We asked for stakeholders to provide input on governance of large biorepositories at the University of California (UC), a public university. We defined state residents as stakeholders and recruited residents from two large metropolitan areas, Los Angeles (LA) and San Francisco (SF). In LA, we recruited English and Spanish speakers; in SF the DCE was conducted in English only. We recruited individuals who had completed the 2009 California Health Interview Survey and were willing to be re-contacted for future studies. Using stratified random sampling (by age, education, race/ethnicity), we contacted 162 potential deliberants of whom 53 agreed to participate and 51 completed the 4-day DCE in June (LA) and September-October (SF), 2013. Each DCE included discussion among deliberants facilitated by a trained staff and simultaneously-translated in LA. Deliberants also received a briefing book describing biorepository operations and regulation. During the final day of the DCE, deliberants voted on governance and oversight recommendations using an audience response system. This paper describes 23 recommendations (of 57 total) that address issues including: educating the public, sharing samples broadly, monitoring researcher behavior, using informative consent procedures, and involving community members in a transparent process of biobank governance. This project demonstrates the feasibility of obtaining meaningful input on biorepository governance from diverse lay stakeholders. Such input should be considered as research institutions respond to changes in biorepository regulation.
The human reference genome is the most widely used resource in human genetics and is due for a major update. Its current structure is a linear composite of merged haplotypes from more than 20 people, ...with a single individual comprising most of the sequence. It contains biases and errors within a framework that does not represent global human genomic variation. A high-quality reference with global representation of common variants, including single-nucleotide variants, structural variants and functional elements, is needed. The Human Pangenome Reference Consortium aims to create a more sophisticated and complete human reference genome with a graph-based, telomere-to-telomere representation of global genomic diversity. Here we leverage innovations in technology, study design and global partnerships with the goal of constructing the highest-possible quality human pangenome reference. Our goal is to improve data representation and streamline analyses to enable routine assembly of complete diploid genomes. With attention to ethical frameworks, the human pangenome reference will contain a more accurate and diverse representation of global genomic variation, improve gene-disease association studies across populations, expand the scope of genomics research to the most repetitive and polymorphic regions of the genome, and serve as the ultimate genetic resource for future biomedical research and precision medicine.
Biological kin share up to half of their genetic material, including predisposition to disease. Thus, variants of clinical significance identified in each individual's genome can implicate an ...exponential number of relatives at potential risk. This has renewed the dilemma over family access to research participant's genetic results, since prevailing US practices treat these as private, controlled by the individual. These individual-based ethics contrast with the family-based ethics - in which genetic information, privacy, and autonomy are considered to be familial - endorsed in UK genomic medicine and by participants in a multi-method study of US research participants presented here. The dilemma reflects a conflict between US legal and ethical frameworks that privilege "the individual" and exclude "the family" versus actual human genetics that are simultaneously individual and familial. Can human genetics succeed in challenging bioethics' hegemonic individualism to recognize and place the family at the center of the room where bioethics happens?
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