Statistical and computational challenges in physical mapping

One of the great success stories of modern molecular genetics has been the ability of biologists to isolate and characterize the genes responsible for serious inherited diseases like Huntington`s disease, cystic fibrosis, and myotonic dystrophy. Instrumental in these efforts has been the construction of so-called {open_quotes}physical maps{close_quotes} of large regions of human chromosomes. Constructing a physical map of a chromosome presents a number of interesting challenges to the computational statistician. In addition to the general ill-posedness of the problem, complications include the size of the data sets, computational complexity, and the pervasiveness of experimental error. The nature of the problem and the presence of many levels of experimental uncertainty make statistical approaches to map construction appealing. Simultaneously, however, the size and combinatorial complexity of the problem make such approaches computationally demanding. In this paper we discuss what physical maps are and describe three different kinds of physical maps, outlining issues which arise in constructing them. In addition, we describe our experience with powerful, interactive statistical computing environments. We found that the ability to create high-level specifications of proposed algorithms which could then be directly executed provided a flexible rapid prototyping facility for developing new statistical models and methods. The ability to check the implementation of an algorithm by comparing its results to that of an executable specification enabled us to rapidly debug both specification and implementation in an environment of changing needs

Maximum Likelihood Estimation in Gaussian Chain Graph Models under the Alternative Markov Property

The AMP Markov property is a recently proposed alternative Markov property for chain graphs. In the case of continuous variables with a joint multivariate Gaussian distribution, it is the AMP rather than the earlier introduced LWF Markov property that is coherent with data-generation by natural block-recursive regressions. In this paper, we show that maximum likelihood estimates in Gaussian AMP chain graph models can be obtained by combining generalized least squares and iterative proportional fitting to an iterative algorithm. In an appendix, we give useful convergence results for iterative partial maximization algorithms that apply in particular to the described algorithm.Comment: 15 pages, article will appear in Scandinavian Journal of Statistic

Analysis of the platypus genome suggests a transposon origin for mammalian imprinting

Comparisons between the platypus and eutherian mammalian genomes provides new insights into how epigenetic imprinting may have evolved in mammalian genomes

A single-sample method for normalizing and combining full-resolution copy numbers from multiple platforms, labs and analysis methods

Motivation: The rapid expansion of whole-genome copy number (CN) studies brings a demand for increased precision and resolution of CN estimates. Recent studies have obtained CN estimates from more than one platform for the same set of samples, and it is natural to want to combine the different estimates in order to meet this demand. Estimates from different platforms show different degrees of attenuation of the true CN changes. Similar differences can be observed in CNs from the same platform run in different labs, or in the same lab, with different analytical methods. This is the reason why it is not straightforward to combine CN estimates from different sources (platforms, labs and analysis methods)

Turning psychology into policy: a case of square pegs and round holes?

This paper problematizes the ways in which the policy process is conceived in published psychological research. It argues that these conceptions of the policy process fail to ade- quately reflect the real-world dynamism and complexity of the processes and practices of social policy-making and implementation. In this context, psychological evidence needs to be seen as one type of evidence (amongst many others). In turn this requires researchers to take account of broader political processes that favour certain types of knowledge and disparage others. Rather than be regarded as objective and scientific, policy in this characterisation is regarded as a motivated form of politics. This multi-layered, multi-level hybrid structure is not immediately amenable to the well-intentioned interventions of psychologists. While the tendency of many psychologists is to overestimate the impact that we can have upon policy formation and implementation, there are examples where psychological theory and research has fed directly into UK policy developments in recent years. This paper draws on the recent Improving Access to Psychological Therapies (IAPT) initiative and the work of personality researcher Adam Perkins on the UK’s social security system to ask whether psychology has a sufficiently elaborated sense of its own evidence base to legitimately seek to influence key national areas of public policy. The article cautions against dramatic changes to policy pre- dicated upon any one reading of the variegated and, at times, contradictory psychological evidence base. It concludes that, in order to meaningfully contribute to the policy develop- ment process in a way which increases equality and social justice, psychologists need to be more strategic in thinking about how their research is likely to be represented and mis- represented in any particular context. Finally some possible directions for psychologists to take for a more meaningful relationship with policy are suggested

Development of a chicken 5 K microarray targeted towards immune function

<p>Abstract</p> <p>Background</p> <p>The development of microarray resources for the chicken is an important step in being able to profile gene expression changes occurring in birds in response to different challenges and stimuli. The creation of an immune-related array is highly valuable in determining the host immune response in relation to infection with a wide variety of bacterial and viral diseases.</p> <p>Results</p> <p>Here we report the development of chicken immune-related cDNA libraries and the subsequent construction of a microarray containing 5190 elements (in duplicate). Clones on the array originate from tissues known to contain high levels of cells related to the immune system, namely Bursa, Peyers patch, thymus and spleen. Represented on the array are genes that are known to cluster with existing chicken ESTs as well as genes that are unique to our libraries. Some of these genes have no known homologies and represent novel genes in the chicken collection. A series of reference genes (ie. genes of known immune function) are also present on the array. Functional annotation data is also provided for as many of the genes on the array as is possible.</p> <p>Conclusion</p> <p>Six new chicken immune cDNA libraries have been created and nearly 10,000 sequences submitted to GenBank [GenBank: <ext-link ext-link-type="gen" ext-link-id="AM063043">AM063043</ext-link>-<ext-link ext-link-type="gen" ext-link-id="AM071350">AM071350</ext-link>; <ext-link ext-link-type="gen" ext-link-id="AM071520">AM071520</ext-link>-<ext-link ext-link-type="gen" ext-link-id="AM072286">AM072286</ext-link>; <ext-link ext-link-type="gen" ext-link-id="AM075249">AM075249</ext-link>-<ext-link ext-link-type="gen" ext-link-id="AM075607">AM075607</ext-link>]. A 5 K immune-related array has been developed from these libraries. Individual clones and arrays are available from the ARK-Genomics resource centre.</p

Securitization in Chinese climate and energy politics

This article provides an overview of securitization in Chinese climate and energy debates. Scholars have debated the merits as well as the potentially problematic implications of securitization, or framing issues as ‘security,’ since the early 1990s. Early concern focused on the potential problems with linking environmental issues with ‘security,’ and the debate has since also turned specifically to the climate and energy. However, it is only recently that this debate has begun to pay attention to China. Energy and climate concerns are of increasing importance to China: the sheer scale of its energy consumption and air pollution struggles dwarf the challenges seen by other states, and its policy choices play a key role in shaping global climate and energy dynamics. Thus, while securitization in the Chinese context is rarely studied, how China frames its energy and climate policy matters. Both energy and climate are taken increasingly seriously, and security plays an increasing role in debates. This review surveys the increasing popularity of linking security with climate and energy issues both in the academic debate on China and in official discourse, and some of the potential implications

What is hindering change? Anticipating the barriers to the adoption of enzyme-based textile processing in a developing country

The study aimed to examine the barriers to embracing enzymatic processing in the garment industry in a developing country. We used the case of Bangladesh, which has the largest garment sector in the world. The research used semi-structured interviews with ten high profile figures in the industry, comprising scientists, manufacturers, enzyme traders and policymakers. We found economic, sociocultural, informational and policy-related barriers to the adoption of enzymatic processing. Attending to each element would benefit manufacturers primarily; this will help identify its strengths and weaknesses to ensure the effective implementation of enzymatic textile processing to obtain optimum results. The study also found that manufacturers’ desire to help improve environmental performance is a factor which could motivate them in adopting green manufacturing innovation. It is expected that regulatory frameworks that encourage innovation - particularly from high social responsiveness and compliances as well as economic and financial incentives - would motivate manufacturers to develop sustainable environmental management strategies that enhance their ability to compete in global markets