Joint and individual variation explained (JIVE) for integrated analysis of multiple data types

Research in several fields now requires the analysis of data sets in which multiple high-dimensional types of data are available for a common set of objects. In particular, The Cancer Genome Atlas (TCGA) includes data from several diverse genomic technologies on the same cancerous tumor samples. In this paper we introduce Joint and Individual Variation Explained (JIVE), a general decomposition of variation for the integrated analysis of such data sets. The decomposition consists of three terms: a low-rank approximation capturing joint variation across data types, low-rank approximations for structured variation individual to each data type, and residual noise. JIVE quantifies the amount of joint variation between data types, reduces the dimensionality of the data and provides new directions for the visual exploration of joint and individual structures. The proposed method represents an extension of Principal Component Analysis and has clear advantages over popular two-block methods such as Canonical Correlation Analysis and Partial Least Squares. A JIVE analysis of gene expression and miRNA data on Glioblastoma Multiforme tumor samples reveals gene-miRNA associations and provides better characterization of tumor types. Data and software are available at https://genome.unc.edu/jive/Comment: Published in at http://dx.doi.org/10.1214/12-AOAS597 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

A Global Community of Courts? Modelling the Use of Persuasive Authority as a Complex Network

There is a growing discussion in the legal literature of an emerging global community of courts composed of a network of increasing judicial dialogue across national borders. We investigate the use of foreign persuasive authority in common law countries by analyzing the network of citations to case law in a corpus of over 1.5 million judgments given by the senior courts of twenty-six common law countries. Our corpus of judgments is derived from data available in the vLex Justis database. In this paper we aim to quantify the flow of jurisprudence across the countries in our corpus and to explore the factors that may influence a judge’s selection of foreign jurisprudence. Utilization of foreign case law varies across the countries in our data, with the courts of some countries presenting higher engagement with foreign jurisprudence than others. Our analysis shows that there has been an upward trend in the use of foreign case law over time, with a marked increase in citations across national borders from the 1990s onward, potentially indicating that increased digital access to foreign judgments has served to facilitate and promote comparative analysis. Not only has the use of foreign case law generally increased over time, the factors that may influence the selection of case law have also evolved, with judges gradually casting their research beyond the most influential and well-known foreign authorities. Notwithstanding that judgments emanating from the United Kingdom (chiefly from the courts of England and Wales) constitute the most frequently consulted body of jurisprudence, we find evidence that domestic courts favor citing the case law of countries that are geographically proximal

Live Coding, Live Notation, Live Performance

This paper/demonstration explores relationships between code, notation including representation, visualisation and performance. Performative aspects of live coding activities are increasingly being investigated as the live coding movement continues to grow and develop. Although live instrumental performance is sometimes included as an accompaniment to live coding, it is often not a fully integrated part of the performance, relying on improvisation and/or basic indicative forms of notation with varying levels of sophistication and universality. Technologies are developing which enable the use of fully explicit music notations as well as more graphic ones, allowing more fully integrated systems of code in and as performance which can also include notations of arbitrary complexity. This itself allows the full skills of instrumental musicians to be utilised and synchronised in the process. This presentation/demonstration presents work and performances already undertaken with these technologies, including technologies for body sensing and data acquisition in the translation of the movements of dancers and musicians into synchronously performable notation, integrated by live and prepared coding. The author together with clarinetist Ian Mitchell present a short live performance utilising these techniques, discuss methods for the dissemination and interpretation of live generated notations and investigate how they take advantage of instrumental musicians’ training-related neuroplasticity skills

Group art therapy as an adjunctive treatment for people with schizophrenia: a randomised controlled trial (MATISSE).

OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of referral to group art therapy plus standard care, compared with referral to an activity group plus standard care and standard care alone, among people with schizophrenia. DESIGN: A three-arm, parallel group, single-blind, pragmatic, randomised controlled trial. Participants were randomised via an independent and remote telephone randomisation service using permuted blocks, stratified by study centre. SETTING: Study participants were recruited from secondary care mental health and social services in four UK centres. PARTICIPANTS: Potential participants were aged 18 years or over, had a clinical diagnosis of schizophrenia, confirmed by an examination of case notes, and provided written informed consent. We excluded those who were unable to speak sufficient English to complete the baseline assessment, those with severe cognitive impairment and those already receiving arts therapy. INTERVENTIONS: Group art therapy was delivered by registered art therapists according to nationally agreed standards. Groups had up to eight members, lasted for 90 minutes and ran for 12 months. Members were given access to a range of art materials and encouraged to use these to express themselves freely. Activity groups were designed to control for the non-specific effects of group art therapy. Group facilitators offered various activities and encouraged participants to collectively select those they wanted to pursue. Standard care involved follow-up from secondary care mental health services and the option of referral to other services, except arts therapies, as required. MAIN OUTCOME MEASURES: Our co-primary outcomes were global functioning (measured using the Global Assessment of Functioning Scale - GAF) and mental health symptoms (measured using the Positive and Negative Syndrome Scale - PANSS) at 24 months. The main secondary outcomes were level of group attendance, social functioning, well-being, health-related quality of life, service utilisation and other costs measured 12 and 24 months after randomisation. RESULTS: Four hundred and seventeen people were recruited, of whom 355 (85%) were followed up at 2 years. Eighty-six (61%) of those randomised to art therapy and 73 (52%) of those randomised to activity groups attended at least one group. No differences in primary outcomes were found between the three study arms. The adjusted mean difference between art therapy and standard care at 24 months was -0.9 [95% confidence interval (CI) -3.8 to 2.1] on the GAF Scale and 0.7 (95% CI -3.1 to 4.6) on the PANSS Scale. Differences in secondary outcomes were not found, except that those referred to an activity group had fewer positive symptoms of schizophrenia at 24 months than those randomised to art therapy. Secondary analysis indicated that attendance at art therapy groups was not associated with improvements in global functioning or mental health. Although the total cost of the art therapy group was lower than the cost of the two comparison groups, referral to group art therapy did not appear to provide a cost-effective use of resources. CONCLUSIONS: Referring people with established schizophrenia to group art therapy as delivered in this randomised trial does not appear to improve global functioning or mental health of patients or provide a more cost-effective use of resources than standard care alone. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 46150447. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 8. See the HTA programme website for further project information

Tumor Evolution in Two Patients with Basal-like Breast Cancer: A Retrospective Genomics Study of Multiple Metastases

Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual

Identification of mRNA isoform switching in breast cancer

Abstract Background Alternative splicing provides a major mechanism to generate protein diversity. Increasing evidence suggests a link of dysregulation of splicing associated with cancer. While previous genomic-based studies demonstrated the expression of a handful of tumor-specific isoforms, genome-wide alterations in the balance between isoforms and cancer subtypes is understudied. Result We systematically analyzed the isoform-level expression patterns and isoform switching events of 819 breast tumor and normal samples assayed by mRNA-seq from TCGA project. On average, 2.2 isoforms per gene were detected and 67.5 % of detected genes (i.e. expressed) showed 1–2 isoforms only. While the majority of isoforms for a given gene were positively correlated with each other and the overall gene level, 470 pairs of isoforms displayed an inverse correlation suggesting a switching event. Most of the isoform switching events were associated with molecular subtypes, including a Basal-like-associated switching in CTNND1. 88 genes showed switching independent of subtypes, among which the isoform pattern of PRICKLE1 was associated with a large genomic signature of biological significance. Conclusion Our results reveal that the majority of genes do not undergo complex mRNA splicing within breast cancers, and that there is a general concordance in isoform and gene expression levels in breast tumors. We identified hundreds of isoform switching events across breast tumors, most of which were associated with differences in tumor subtypes. As exemplified by the detailed analysis of CTNND1 and PRICKLE1, these isoform switching events potentially provide new insights into the post-transcriptional regulatory mechanisms of tumor subtypes and cancer biology

Improving statistical inference on pathogen densities estimated by quantitative molecular methods: malaria gametocytaemia as a case study

BACKGROUND: Quantitative molecular methods (QMMs) such as quantitative real-time polymerase chain reaction (q-PCR), reverse-transcriptase PCR (qRT-PCR) and quantitative nucleic acid sequence-based amplification (QT-NASBA) are increasingly used to estimate pathogen density in a variety of clinical and epidemiological contexts. These methods are often classified as semi-quantitative, yet estimates of reliability or sensitivity are seldom reported. Here, a statistical framework is developed for assessing the reliability (uncertainty) of pathogen densities estimated using QMMs and the associated diagnostic sensitivity. The method is illustrated with quantification of Plasmodium falciparum gametocytaemia by QT-NASBA. RESULTS: The reliability of pathogen (e.g. gametocyte) densities, and the accompanying diagnostic sensitivity, estimated by two contrasting statistical calibration techniques, are compared; a traditional method and a mixed model Bayesian approach. The latter accounts for statistical dependence of QMM assays run under identical laboratory protocols and permits structural modelling of experimental measurements, allowing precision to vary with pathogen density. Traditional calibration cannot account for inter-assay variability arising from imperfect QMMs and generates estimates of pathogen density that have poor reliability, are variable among assays and inaccurately reflect diagnostic sensitivity. The Bayesian mixed model approach assimilates information from replica QMM assays, improving reliability and inter-assay homogeneity, providing an accurate appraisal of quantitative and diagnostic performance. CONCLUSIONS: Bayesian mixed model statistical calibration supersedes traditional techniques in the context of QMM-derived estimates of pathogen density, offering the potential to improve substantially the depth and quality of clinical and epidemiological inference for a wide variety of pathogens