Sourcepredict: Prediction of metagenomic sample sources using dimension reduction followed by machine learning classification

SourcePredict is a Python package distributed through Conda, to classify and predict the origin of metagenomic samples, given a reference dataset of known origins, a problem also known as source tracking. DNA shotgun sequencing of human, animal, and environmental samples has opened up new doors to explore the diversity of life in these different environments, a field known as metagenomics (Hugenholtz & Tyson, 2008). One aspect of metagenomics is investigating the community composition of organisms within a sequencing sample with tools known as taxonomic classifiers, such as Kraken (Wood & Salzberg, 2014). In cases where the origin of a metagenomic sample, its source, is unknown, it is often part of the research question to predict and/or confirm the source. For example, in microbial archaelogy, it is sometimes necessary to rely on metagenomics to validate the source of paleofaeces. Using samples of known sources, a reference dataset can be established with the taxonomic composition of the samples, i.e., the organisms identified in the samples as features, and the sources of the samples as class labels. With this reference dataset, a machine learning algorithm can be trained to predict the source of unknown samples (sinks) from their taxonomic composition. Other tools used to perform the prediction of a sample source already exist, such as Source- Tracker (Knights et al., 2011), which employs Gibbs sampling. However, the Sourcepredict results are more easily interpreted since the samples are embedded in a human observable low-dimensional space. This embedding is performed by a dimension reduction algorithm followed by K-Nearest-Neighbours (KNN) classification.Summary Method - Prediction of the proportion of unknown sources - Prediction of the proportion of known sources - Combining unknown and source proportion

Controlled access under review : improving the governance of genomic data access

In parallel with massive genomic data production, data sharing practices have rapidly expanded over the last decade. To ensure authorized access to data, access review by data access committees (DACs) has been utilized as one potential solution. Here we discuss core elements to be integrated into the fabric of access review by both established and emerging DACs in order to foster fair, efficient, and responsible access to datasets. We particularly highlight the fact that the access review process could be adversely influenced by the potential conflicts of interest of data producers, particularly when they are directly involved in DACs management. Therefore, in structuring DACs and access procedures, possible data withholding by data producers should receive thorough attention

PyDamage: automated ancient damage identification and estimation for contigs in ancient DNAde novoassembly

DNA de novo assembly can be used to reconstruct longer stretches of DNA (contigs), including genes and even genomes, from short DNA sequencing reads. Applying this technique to metagenomic data derived from archaeological remains, such as paleofeces and dental calculus, we can investigate past microbiome functional diversity that may be absent or underrepresented in the modern microbiome gene catalogue. However, compared to modern samples, ancient samples are often burdened with environmental contamination, resulting in metagenomic datasets that represent mixtures of ancient and modern DNA. The ability to rapidly and reliably establish the authenticity and integrity of ancient samples is essential for ancient DNA studies, and the ability to distinguish between ancient and modern sequences is particularly important for ancient microbiome studies. Characteristic patterns of ancient DNA damage, namely DNA fragmentation and cytosine deamination (observed as C-to-T transitions) are typically used to authenticate ancient samples and sequences, but existing tools for inspecting and filtering aDNA damage either compute it at the read level, which leads to high data loss and lower quality when used in combination with de novo assembly, or require manual inspection, which is impractical for ancient assemblies that typically contain tens to hundreds of thousands of contigs. To address these challenges, we designed PyDamage, a robust, automated approach for aDNA damage estimation and authentication of de novo assembled aDNA. PyDamage uses a likelihood ratio based approach to discriminate between truly ancient contigs and contigs originating from modern contamination. We test PyDamage on both on simulated aDNA data and archaeological paleofeces, and we demonstrate its ability to reliably and automatically identify contigs bearing DNA damage characteristic of aDNA. Coupled with aDNA de novo assembly, Pydamage opens up new doors to explore functional diversity in ancient metagenomic datasets

Genetic testing of children for adult-onset conditions: opinions of the British adult population and implications for clinical practice

This study set out to explore the attitudes of a representative sample of the British public towards genetic testing in children to predict disease in the future. We sought opinions about genetic testing for adult-onset conditions for which no prevention/treatment is available during childhood, and about genetic 'carrier' status to assess future reproductive risks. The study also examined participants' level of agreement with the reasons professional organisations give in favour of deferring such testing. Participants (n=2998) completed a specially designed questionnaire, distributed by email. Nearly half of the sample (47%) agreed that parents should be able to test their child for adult-onset conditions, even if there is no treatment or prevention at time of testing. This runs contrary to professional guidance about genetic testing in children. Testing for carrier status was supported by a larger proportion (60%). A child's future ability to decide for her/himself if and when to be tested was the least supported argument in favour of deferring testing.European Journal of Human Genetics advance online publication, 5 November 2014; doi:10.1038/ejhg.2014.221

Marginally scientific? Genetic testing of children and adolescents for lifestyle and health promotion

Abstract not availableTimothy Caulfield, Pascal Borry, Maeghan Toews, Bernice S. Elger, Henry T. Greely and Amy McGuir

Testing the Children: Do Non-Genetic Health-Care Providers Differ in Their Decision to Advise Genetic Presymptomatic Testing on Minors? A Cross-Sectional Study in Five Countries in the European Union

BACKGROUND: Within Europe many guidelines exist regarding the genetic testing of minors. Predictive and presymptomatic genetic testing of minors is recommended for disorders for which medical intervention/preventive measures exist, and for which early detection improves future medical health. AIM: This study, which is part of the larger 5th EU-framework "genetic education" (GenEd) study, aimed to evaluate the self-reported responses of nongenetic health-care providers in five different EU countries (Germany, France, Sweden, the United Kingdom, and the Netherlands) when confronted with a parent requesting presymptomatic testing on a minor child for a treatable disease. METHODS: A cross-sectional study design using postal, structured scenario-based questionnaires that were sent to 8129 general practitioners (GPs) and pediatricians, between July 2004 and October 2004, addressing self-reported management of a genetic case for which early medical intervention during childhood is beneficial, involving a minor. RESULTS: Most practitioners agreed on testing the oldest child, aged 12 years (81.5% for GPs and 87.2% for pediatricians), and not testing the youngest child, aged 6 months (72.6% for GPs and 61.3% for pediatricians). After multivariate adjustment there were statistical differences between countries in recommending a genetic test for the child at the age of 8 years. Pediatricians in France (50%) and Germany (58%) would recommend a test, whereas in the United Kingdom (22%), Sweden (30%), and the Netherlands (32%) they would not. CONCLUSION: Even though presymptomatic genetic testing in minors is recommended for disorders for which medical intervention exists, EU physicians are uncertain at what age starting to do so in young children

Decision making and experiences of young adults undergoing presymptomatic genetic testing for familial cancer: A longitudinal grounded theory study

Enabling informed choice is an essential component of care when offering young adults presymptomatic testing for a genetic condition. A systematic review on this topic revealed that many young adults grew up with little information regarding their genetic risk and that parents had applied pressure to them during the testing decision-making process. However, none of the studies retrieved were conducted in South European countries. To address this gap, we undertook a qualitative study based on grounded theory to explore the psychosocial implications of presymptomatic testing for hereditary cancer in Italian young adults aged 18-30 years. Interviews were conducted on three occasions: 1 month before counselling, and 2 weeks and 6 months after results. Data were coded and grouped under themes. A total of 42 interviews were conducted. Four themes emerged: knowledge, genetic counselling process, decision making and dealing with test results. Although participants grew up with little or no information about their genetic risk, none expressed regret at having the test at a young age. Pre-test counselling was appreciated as a source of information, rather than support for decision making. Decisions were often made autonomously and sometimes conflicted with parents' wishes. Participants reported no changes in health behaviours after testing. This evidence highlights the need for a comprehensive, longitudinal counselling process with appropriate timing and setting, which supports 'parent-to-offspring' risk communication first and decision making by young adults about presymptomatic testing and risk management afterwards. In conclusion, it is clear that counselling approaches for presymptomatic testing may require modification both for young adults and their parents. © 2017 European Society of Human Genetics

The challenges of the expanded availability of genomic information: an agenda-setting paper

Rapid advances in microarray and sequencing technologies are making genotyping and genome sequencing more affordable and readily available. There is an expectation that genomic sequencing technologies improve personalized diagnosis and personalized drug therapy. Concurrently, provision of direct-to-consumer genetic testing by commercial providers has enabled individuals’ direct access to their genomic data. The expanded availability of genomic data is perceived as influencing the relationship between the various parties involved including healthcare professionals, researchers, patients, individuals, families, industry, and government. This results in a need to revisit their roles and responsibilities. In a 1-day agenda-setting meeting organized by the COST Action IS1303 “Citizen’s Health through public-private Initiatives: Public health, Market and Ethical perspectives,” participants discussed the main challenges associated with the expanded availability of genomic information, with a specific focus on public-private partnerships, and provided an outline from which to discuss in detail the identified challenges. This paper summarizes the points raised at this meeting in five main parts and highlights the key cross-cutting themes. In light of the increasing availability of genomic information, it is expected that this paper will provide timely direction for future research and policy making in this area.Funding Deborah Mascalzoni is supported under Grant Agreement number 305444. Álvaro Mendes is supported by the FCT—The Portuguese Foundation for Science and Technology under postdoctoral grant SFRH/BPD/88647/2012. Isabelle Budin-Ljøsne receives support from the National Research and Innovation Platform for Personalized Cancer Medicine funded by The Research Council of Norway (NFR BIOTEK2021/ES495029) and Biobank Norway funded by The Research Council of Norway—grant number 245464. Heidi Carmen Howard is partly supported by supported by the Swedish Foundation for Humanities and Social Science under grant M13-0260:1), the Biobanking and Molecular Resource Infrastructure of Sweden (BBMRI.se) and the BBMRI-ERIC. Brígida Riso is supported by the Portuguese Foundation for Science and Technology (FCT) under the PhD grant SFRH/BD/100779/2014. Heidi Beate Bentzen receives support from the project Legal Regulation of Information Processing relating to Personalized Cancer Medicine funded by The Research Council of Norway BIOTEK2021/238999