GenePath: a System for Automated Construction of Genetic Networks from Mutant Data

Motivation: Genetic pathways are often used in the analysis of biological phenomena. In classical genetics, they are constructed manually from experimental data on mutants. The field lacks formalism to guide such analysis, and accounting for all the data becomes complicated when large amounts of data are considered. Results: We have developed GenePath, an intelligent assistant that mimics expert geneticists in the analysis of genetic data. GenePath employs expert-defined patterns to uncover gene relations from the data, and uses these relations as constraints that guide the search for a plausible genetic network. GenePath provides formalism to genetic data analysis, facilitates the consideration of all the available data in a consistent and systematic manner, and aids in the examination of the large number of possible consequences of a planned experiment. It also provides an explanation mechanism that traces back every finding to the pertinent data. GenePath was successfully tested on several genetic problems. Availability: GenePath can be accessed at http://genepath.org. Supplementary information: Supplementary material is available at http://genepath.org/bi-supp

Evaluation of forensic DNA traces when propositions of interest relate to activities: analysis and discussion of recurrent concerns

When forensic scientists evaluate and report on the probative strength of single DNA traces, they commonly rely on only one number, expressing the rarity of the DNA profile in the population of interest. This is so because the focus is on propositions regarding the source of the recovered trace material, such as “the person of interest is the source of the crime stain.” In particular, when the alternative proposition is “an unknown person is the source of the crime stain,” one is directed to think about the rarity of the profile. However, in the era of DNA profiling technology capable of producing results from small quantities of trace material (i.e., non-visible staining) that is subject to easy and ubiquitous modes of transfer, the issue of source is becoming less central, to the point that it is often not contested. There is now a shift from the question “whose DNA is this?” to the question “how did it get there?” As a consequence, recipients of expert information are now very much in need of assistance with the evaluation of the meaning and probative strength of DNA profiling results when the competing propositions of interest refer to different activities. This need is widely demonstrated in day-to-day forensic practice and is also voiced in specialized literature. Yet many forensic scientists remain reluctant to assess their results given propositions that relate to different activities. Some scientists consider evaluations beyond the issue of source as being overly speculative, because of the lack of relevant data and knowledge regarding phenomena and mechanisms of transfer, persistence and background of DNA. Similarly, encouragements to deal with these activity issues, expressed in a recently released European guideline on evaluative reporting (Willis et al., 2015), which highlights the need for rethinking current practice, are sometimes viewed skeptically or are not considered feasible. In this discussion paper, we select and discuss recurrent skeptical views brought to our attention, as well as some of the alternative solutions that have been suggested. We will argue that the way forward is to address now, rather than later, the challenges associated with the evaluation of DNA results (from small quantities of trace material) in light of different activities to prevent them being misrepresented in court

The Alliance of Genome Resources: Building a Modern Data Ecosystem for Model Organism Databases.

Model organisms are essential experimental platforms for discovering gene functions, defining protein and genetic networks, uncovering functional consequences of human genome variation, and for modeling human disease. For decades, researchers who use model organisms have relied on Model Organism Databases (MODs) and the Gene Ontology Consortium (GOC) for expertly curated annotations, and for access to integrated genomic and biological information obtained from the scientific literature and public data archives. Through the development and enforcement of data and semantic standards, these genome resources provide rapid access to the collected knowledge of model organisms in human readable and computation-ready formats that would otherwise require countless hours for individual researchers to assemble on their own. Since their inception, the MODs for the predominant biomedical model organisms [Mus sp (laboratory mouse), Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, Danio rerio, and Rattus norvegicus] along with the GOC have operated as a network of independent, highly collaborative genome resources. In 2016, these six MODs and the GOC joined forces as the Alliance of Genome Resources (the Alliance). By implementing shared programmatic access methods and data-specific web pages with a unified "look and feel," the Alliance is tackling barriers that have limited the ability of researchers to easily compare common data types and annotations across model organisms. To adapt to the rapidly changing landscape for evaluating and funding core data resources, the Alliance is building a modern, extensible, and operationally efficient "knowledge commons" for model organisms using shared, modular infrastructure

Innate talents: reality or myth?

Talents that selectively facilitate the acquisition of high levels of skill are said to be present in some children but not others. The evidence for this includes biological correlates of specific abilities, certain rare abilities in autistic savants, and the seemingly spontaneous emergence of exceptional abilities in young children, but there is also contrary evidence indicating an absence of early precursors of high skill levels. An analysis of positive and negative evidence and arguments suggests that differences in early experiences, preferences, opportunities, habits, training, and practice are the real determinants of excellence

Dilemmas in fetal medicine: premature application of technology or responding to womens choice?

Copyright @ 2006 The Author.It is argued that innovative health technologies (IHTs) may be changing the roles of both patients and health practitioners, and raising new issues, including ethical, legal and social dilemmas. This paper focuses on the innovative area of fetal medicine. All fetal treatment necessitates accessing the fetus through the pregnant woman's body, and non-surgical treatments have long been a part of pregnancy care. However, recent developments in this area, including the increasing routinisation of sophisticated antenatal ultrasound screening and the introduction of treatments including fetal surgery, may mark a shift in this specialty. The paper explores such shifts from the perspectives of medical and midwifery practitioners working in two Fetal Medicine Units. It examines the apparent effects of the orientation of fetal medicine on prevalent conceptualisations of the maternal-fetal relationship, and some of the consequences of this. It is argued that new forms of uncertainty, including complex risk and diagnostic information, and uncertain prognostic predictions set within the rhetoric of non-directive counselling and women's choice, are leading to unprecedented ethical dilemmas within this area. More widespread debate about such potential dilemmas needs to take place before, rather than following their introduction.This study is supported by the Wellcome Trust Biomedical Ethics programme and the ESRC Innovative Health Technologies Programme (grant number L218252042)

How Prosecutors and Defense Attorneys Differ in Their Use of Neuroscience Evidence

Much of the public debate surrounding the intersection of neuroscience and criminal law is based on assumptions about how prosecutors and defense attorneys differ in their use of neuroscience evidence. For example, according to some commentators, the defense’s use of neuroscience evidence will abdicate criminals of all responsibility for their offenses. In contrast, the prosecution’s use of that same evidence will unfairly punish the most vulnerable defendants as unfixable future dangers to society. This “double- edged sword” view of neuroscience evidence is important for flagging concerns about the law’s construction of criminal responsibility and punishment: it demonstrates that the same information about the defendant can either be mitigating or aggravating depending on who is raising it. Yet empirical assessments of legal decisions reveal a far more nuanced reality, showing that public beliefs about the impact of neuroscience on the criminal law can often be wrong. This Article takes an evidence-based and multidisciplinary approach to examining how courts respond to neuroscience evidence in capital cases when the defense presents it to argue that the defendant’s mental state at the time of the crime was below the given legal requisite due to some neurologic or cognitive deficiency