USE OF HIDDEN MARKOV MODELS FOR QTL MAPPING

An important aspect of the QTL mapping problem is the treatment of missing genotype data. If complete genotype data were available, QTL mapping would reduce to the problem of model selection in linear regression. However, in the consideration of loci in the intervals between the available genetic markers, genotype data is inherently missing. Even at the typed genetic markers, genotype data is seldom complete, as a result of failures in the genotyping assays or for the sake of economy (for example, in the case of selective genotyping, where only individuals with extreme phenotypes are genotyped). We discuss the use of algorithms developed for hidden Markov models (HMMs) to deal with the missing genotype data problem.

Bayesian Hidden Markov Modeling of Array CGH Data

Genomic alterations have been linked to the development and progression of cancer. The technique of Comparative Genomic Hybridization (CGH) yields data consisting of fluorescence intensity ratios of test and reference DNA samples. The intensity ratios provide information about the number of copies in DNA. Practical issues such as the contamination of tumor cells in tissue specimens and normalization errors necessitate the use of statistics for learning about the genomic alterations from array-CGH data. As increasing amounts of array CGH data become available, there is a growing need for automated algorithms for characterizing genomic profiles. Specifically, there is a need for algorithms that can identify gains and losses in the number of copies based on statistical considerations, rather than merely detect trends in the data. We adopt a Bayesian approach, relying on the hidden Markov model to account for the inherent dependence in the intensity ratios. Posterior inferences are made about gains and losses in copy number. Localized amplifications (associated with oncogene mutations) and deletions (associated with mutations of tumor suppressors) are identified using posterior probabilities. Global trends such as extended regions of altered copy number are detected. Since the posterior distribution is analytically intractable, we implement a Metropolis-within-Gibbs algorithm for efficient simulation-based inference. Publicly available data on pancreatic adenocarcinoma, glioblastoma multiforme and breast cancer are analyzed, and comparisons are made with some widely-used algorithms to illustrate the reliability and success of the technique.

A HIDDEN MARKOV MODEL FOR JOINT ESTIMATION OF GENOTYPE AND COPY NUMBER IN HIGH-THROUGHPUT SNP CHIPS

Amplifications and deletions of chromosomal DNA, as well as copy-neutral loss of heterozygosity have been associated with diseases processes. High-throughput single nucleotide polymorphism (SNP) arrays are useful for making genome-wide estimates of copy number and genotype calls. Because neighboring SNPs in high throughput SNP arrays are likely to have dependent copy number and genotype due to the underlying haplotype structure and linkage disequilibrium, hidden Markov models (HMM) may be useful for improving genotype calls and copy number estimates that do not incorporate information from nearby SNPs. We improve previous approaches that utilize a HMM framework for inference in high throughput SNP arrays by integrating copy number, genotype calls, and the corresponding confidence scores when available. Using simulated data, we demonstrate how confidence scores control smoothing in a probabilistic framework. Software for fitting HMMs to SNP array data is available in the R package ICE.

A rare anomaly of the anterior communicating artery complex hidden by a large broad-neck aneurysm and disclosed by three-dimensional rotational angiography

Double fenestration of the anterior communicating artery (ACoA) complex associated with an aneurysm is a very rare finding and is usually caused by ACoA duplication and the presence of a median artery of the corpus callosum (MACC). We present a patient in whom double fenestration was not associated with ACoA duplication or even with MACC, representing therefore, a previously unreported anatomic variation. A 43 year old woman experienced sudden headache and the CT scans showed subarachnoid haemorrhage (SAH). On admission, her clinical condition was consistent with Hunt and Hess grade II. Conventional digital subtraction angiography (DSA) was performed and revealed multiple intracranial aneurysms arising from both middle cerebral arteries (MCA) and from the ACoA. Three-dimensional rotational angiography (3D-RA) disclosed a double fenestration of the ACoA complex which was missed by DSA. The patient underwent a classic pterional approach in order to achieve occlusion of both left MCA and ACoA aneurysms by surgical clipping. The post-operative period was uneventful. A rare anatomical variation characterised by a double fenestration not associated with ACoA duplication or MACC is described. The DSA images missed the double fenestration which was disclosed by 3D-RA, indicating the importance of 3D-RA in the diagnosis and surgical planning of intracranial aneurysms.

Light Transport in PT-invariant Photonic Structures with Hidden Symmetries

We introduce a recursive bosonic quantization technique for generating classical PT photonic structures that possess hidden symmetries and higher order exceptional points. We study light transport in these geometries and we demonstrate that perfect state transfer is possible only for certain initial conditions. Moreover, we show that for the same propagation direction, left and right coherent transports are not symmetric with field amplitudes following two different trajectories. A general scheme for identifying the conservation laws in such PT-symmetric photonic networks is also presented.

Homelessness, Social Work, Social Policy and the Print Media in Australian Cities

Homelessness is a significant social problem worldwide. This paper describes an Australian study that examined print media representations of homelessness and social work, social policy and social work responses to homelessness in three Australian cities. The research included a content analysis of seven Australian newspapers and semi-structured interviews with 39 social workers employed in the field of homelessness in Adelaide, Melbourne and Sydney. The detailed results of these studies have been published separately elsewhere. This paper reports on how discourses in the print media, social policy and social work practice co-exist in constructing homelessness as a particular social problem, influencing social work responses to homelessness. The research found that individualism is central to many dominant discourses evident in the print media, social policy and social work practice, and that social work is practiced within unequal power relations embedded in organisational contexts.

Beyond the Margins: Analyzing Social Exclusion with a Homeless Client Dataset

A great share of literature on social exclusion has been based mainly on the analysis of official survey data. Whereas these efforts have provided insights into the characteristics and conditions of those people living at the margins of mainstream social relations, they have however failed to encompass those who live beyond these very margins. Meanwhile, research on these hidden subpopulations, such as homeless and other vulnerable groups, remains generally less abundant and is significantly detached from the theoretical core of the debate on social exclusion. The concern about these shortcomings lies at the heart of our research. We seek to bring some light to the area by using data made available by an organization that provides services to people experiencing homelessness in Barcelona (Spain). The data sample contains clients in early stages of exclusion and others in chronic situations. Thus, we attempt to identify some of the variables that operate in preventing the "chronification" of those individuals in situation of social exclusion. Our findings suggest that certain variables such as educational level, income and housing type, which are considered to be central predictors in the analysis of poverty, behave differently when analyzing differences between stages of social exclusion. Although these results cannot be extrapolated to the whole Spanish or European reality, they could provide useful insight for future investigations on this topic.