No major flaws in "Identification of individuals by trait prediction using whole-genome sequencing data"

In a recently published PNAS article, we studied the identifiability of genomic samples using machine learning methods [Lippert et al., 2017]. In a response, Erlich [2017] argued that our work contained major flaws. The main technical critique of Erlich [2017] builds on a simulation experiment that shows that our proposed algorithm, which uses only a genomic sample for identification, performed no better than a strategy that uses demographic variables. Below, we show why this comparison is misleading and provide a detailed discussion of the key critical points in our analyses that have been brought up in Erlich [2017] and in the media. Further, not only faces may be derived from DNA, but a wide range of phenotypes and demographic variables. In this light, the main contribution of Lippert et al. [2017] is an algorithm that identifies genomes of individuals by combining multiple DNA-based predictive models for a myriad of traits

Analyzing multitarget activity landscapes using protein-ligand interaction fingerprints: interaction cliffs.

This is the original submitted version, before peer review. The final peer-reviewed version is available from ACS at http://pubs.acs.org/doi/abs/10.1021/ci500721x.Activity landscape modeling is mostly a descriptive technique that allows rationalizing continuous and discontinuous SARs. Nevertheless, the interpretation of some landscape features, especially of activity cliffs, is not straightforward. As the nature of activity cliffs depends on the ligand and the target, information regarding both should be included in the analysis. A specific way to include this information is using protein-ligand interaction fingerprints (IFPs). In this paper we report the activity landscape modeling of 507 ligand-kinase complexes (from the KLIFS database) including IFP, which facilitates the analysis and interpretation of activity cliffs. Here we introduce the structure-activity-interaction similarity (SAIS) maps that incorporate information on ligand-target contact similarity. We also introduce the concept of interaction cliffs defined as ligand-target complexes with high structural and interaction similarity but have a large potency difference of the ligands. Moreover, the information retrieved regarding the specific interaction allowed the identification of activity cliff hot spots, which help to rationalize activity cliffs from the target point of view. In general, the information provided by IFPs provides a structure-based understanding of some activity landscape features. This paper shows examples of analyses that can be carried out when IFPs are added to the activity landscape model.M-L is very grateful to CONACyT (No. 217442/312933) and the Cambridge Overseas Trust for funding. AB thanks Unilever for funding and the European Research Council for a Starting Grant (ERC-2013- StG-336159 MIXTURE). J.L.M-F. is grateful to the School of Chemistry, Department of Pharmacy of the National Autonomous University of Mexico (UNAM) for support. This work was supported by a scholarship from the Secretariat of Public Education and the Mexican government

Eating disorders: the current status of molecular genetic research

Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders characterized by disordered eating behavior where the patient’s attitude towards weight and shape, as well as their perception of body shape, are disturbed. Formal genetic studies on twins and families suggested a substantial genetic influence for AN and BN. Candidate gene studies have initially focused on the serotonergic and other central neurotransmitter systems and on genes involved in body weight regulation. Hardly any of the positive findings achieved in these studies were unequivocally confirmed or substantiated in meta-analyses. This might be due to too small sample sizes and thus low power and/or the genes underlying eating disorders have not yet been analyzed. However, some studies that also used subphenotypes (e.g., restricting type of AN) led to more specific results; however, confirmation is as yet mostly lacking. Systematic genome-wide linkage scans based on families with at least two individuals with an eating disorder (AN or BN) revealed initial linkage regions on chromosomes 1, 3 and 4 (AN) and 10p (BN). Analyses on candidate genes in the chromosome 1 linkage region led to the (as yet unconfirmed) identification of certain variants associated with AN. Genome-wide association studies are under way and will presumably help to identify genes and pathways involved in these eating disorders. The elucidation of the molecular mechanisms underlying eating disorders might improve therapeutic approaches

The physical properties of minor aquifers in England and Wales

This report is the result of a three-year collaborative project between the British Geological Survey and the Environment Agency. The aim of the project has been to collect, collate and present information concerning the physical hydraulic properties of the minor aquifers in England and Wales. These properties include hydraulic conductivity, porosity, transmissivity and storage coefficient. In addition, specific capacity (yield per unit drawdown) values are included for many of the formations described, together with yields for those formations where aquifer properties data are sparse. Although the parameters studied were limited in number, the study has proven to be complex for several reasons. Firstly the aquifers themselves are hydraulically complicated. They are bodies of rock, sometimes with indeterminate boundaries, which are heterogeneous either because of sedimentological factors in the case of the Cainozoic aquifers, or because of the effects of fracturing in older formations. This heterogeneity presents several problems. Firstly, hydraulic tests on such materials often violate the classical assumptions used in the test analysis, and the complexity of the aquifers makes interpolation between data points difficult. Secondly, the physical properties of the aquifers are often scale dependent, so that the value of a parameter at one scale may not be appropriate for use at a larger or smaller scale. Thirdly, there are problems of data quality and quantity which are particularly significant for these smaller aquifers. The quality of the pumping tests is variable and many results are from short duration pumping tests which are designed more to assess the yields of boreholes than to examine the properties of the aquifer. Also, data can be very irregularly distributed, being a product mainly of the evolving requirements of groundwater users and not of well-planned resource assessments. This irregular spacing can be both vertical as well as lateral, as in the case of thick structurally complex sequences with only scattered productive horizons. Awareness of these inherent hydrogeological factors dictated the project’s approach, which was to collect both data and knowledge about the aquifers. This permits the report to describe not only the magnitudes and variability of the aquifer parameters at a given tested locality, but also to provide some insight into factors controlling the properties, so that the results can be more confidently extrapolated. Project resources were therefore initially employed in data collection. This involved a detailed search through Agency records, with additional information from BGS, published and unpublished literature. Most of the data obtained were from analysed pumping tests, the results of which were entered in a database. The latter originally housed data on the major aquifers, collected under a preceding project, but the database needed to be significantly altered and expanded so as to manage efficiently the much larger number of aquifers involved. It was also linked with the BGS Core Analysis Database. The result comprises the National Aquifer Properties Database which is now a major UK geoscience resource, with data from more than 8000 pumping test analyses at over 8250 sites. The second main strand of the project was the collection and summarising of knowledge about the aquifers. In addition to the collection of reports of hydrogeological studies and a literature survey, expert opinion was canvassed. The latter is a vital source of information that is not often published. The results of these two approaches are synthesised in this report. After the introductory sections each chapter takes the form of a detailed review of the physical properties of a group of minor aquifers, subdivided as appropriate on stratigraphic or geographical grounds. The chapters are arranged in order of increasing age. The purpose of the review is to present the magnitudes and variability of the data (mainly from the database, but with other examples) in the context of current understanding of the aquifer systems involved and the controls on the data. To that end the review includes geological, geographical and physical hydrogeological aspects of the aquifers. Useful summaries of data from the database are included on the accompanying CD-ROM. The intention of the report is therefore to acquaint the reader with the aquifer properties data values that characterise the aquifers in the context of what is known about the complexities of their hydraulic structure and the physical controls on the data. The reader is specifically dissuaded from taking raw values out of context. A further purpose of the report is provide a comprehensive set of references by which the reader can obtain more detailed information about particular areas of interest in an aquifer. As a result of the collection and review of information about the physical properties of the minor aquifers in England and Wales, it is apparent that there are many areas in which knowledge is inadequate. For example, a critical comparison of the equivalent aquifer systems in the London and Hampshire basins was not possible in other than the most general terms. Similarly, the lateral variability in aquifer properties in the Lower Cretaceous aquifers of the Weald is suspected to arise partly from fault-controlled compartmentalisation, but the role of the faults is not well enough understood for predictive purposes. For all the effort expended on geological characterisation over almost two centuries of detailed study of English Jurassic rocks, the flow systems of the numerous arenaceous and carbonate minor aquifers of that system are in general poorly characterised. Very localised borehole development and the effects of tapping complex multi-aquifer sequences mean that the fracture-dominant, structurally-affected systems of older rocks of Palaeozoic age are in many cases barely conceptualised. Such gaps in our knowledge are inevitable considering the paucity of data. Nevertheless, the project has provided the first opportunity to review comprehensively the aquifer properties of this second rank of British aquifers whose role is so important in providing local sources of water supply for both private and public use