On testing the significance of sets of genes

This paper discusses the problem of identifying differentially expressed groups of genes from a microarray experiment. The groups of genes are externally defined, for example, sets of gene pathways derived from biological databases. Our starting point is the interesting Gene Set Enrichment Analysis (GSEA) procedure of Subramanian et al. [Proc. Natl. Acad. Sci. USA 102 (2005) 15545--15550]. We study the problem in some generality and propose two potential improvements to GSEA: the maxmean statistic for summarizing gene-sets, and restandardization for more accurate inferences. We discuss a variety of examples and extensions, including the use of gene-set scores for class predictions. We also describe a new R language package GSA that implements our ideas.Comment: Published at http://dx.doi.org/10.1214/07-AOAS101 in the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Discussion of "Least angle regression" by Efron et al

Discussion of ``Least angle regression'' by Efron et al. [math.ST/0406456

An extended class of minimax generalized Bayes estimators of regression coefficients

We derive minimax generalized Bayes estimators of regression coefficients in the general linear model with spherically symmetric errors under invariant quadratic loss for the case of unknown scale. The class of estimators generalizes the class considered in Maruyama and Strawderman (2005) to include non-monotone shrinkage functions

Anterior eye health recording.

AIMS: To survey eye care practitioners from around the world regarding their current practice for anterior eye health recording to inform guidelines on best practice. METHODS: The on-line survey examined the reported use of: word descriptions, sketching, grading scales or photographs; paper or computerised record cards and whether these were guided by proforma headings; grading scale choice, signs graded, level of precision, regional grading; and how much time eye care practitioners spent on average on anterior eye health recording. RESULTS: Eight hundred and nine eye care practitioners from across the world completed the survey. Word description (p<0.001), sketches (p=0.002) and grading scales (p<0.001) were used more for recording the anterior eye health of contact lens patients than other patients, but photography was used similarly (p=0.132). Of the respondents, 84.5% used a grading scale, 13.5% using two, with the original Efron (51.6%) and CCLRU/Brien-Holden-Vision-Institute (48.5%) being the most popular. The median features graded was 11 (range 1-23), frequency from 91.6% (bulbar hyperaemia) to 19.6% (endothelial blebs), with most practitioners grading to the nearest unit (47.4%) and just 14.7% to one decimal place. The average time taken to report anterior eye health was reported to be 6.8±5.7 min, with the maximum time available 14.0±11 min. CONCLUSIONS: Developed practice and research evidence allows best practice guidelines for anterior eye health recording to be recommended. It is recommended to: record which grading scale is used; always grade to one decimal place, record what you see live rather than based on how you intend to manage a condition; grade bulbar and limbal hyperaemia, limbal neovascularisation, conjunctival papillary redness and roughness (in white light to assess colouration with fluorescein instilled to aid visualisation of papillae/follicles), blepharitis, meibomian gland dysfunction and sketch staining (both corneal and conjunctival) at every visit. Record other anterior eye features only if they are remarkable, but indicate that the key tissue which have been examined

Resistance Mutations to Zidovudine and Saquinavir in Patients Receiving Zidovudine plus Saquinavir or Zidovudine and Zalcitabine plus Saquinavir in AIDS Clinical Trials Group 229

The relationships among treatment regimens, plasma human immunodeficiency virus (HIV) RNA levels, and resistance mutations to saquinavir (codons 48 and 90) and zidovudine (codon 215) were examined in a cohort of 144 patients from the AIDS Clinical Trials Group 229 study. After 24-40 weeks of therapy, no patients who had received the two-drug combination (zidovudine plus saquinavir) had only codon 48 mutations, 45.8% had only codon 90 mutations, and 8.3% had both codon 48 and 90 mutations. Mutations developed by patients who had received the three-drug combination (zidovudine and zalcitabine plus saquinavir) were codon 48 alone in 1.4%, codon 90 alone in 33.3%, and both codons 48 and 90 in 4.2%. The difference between the groups showed a trend toward reduced mutations with three versus two drugs but did not reach significance (p = .11, two-sided χ2). Higher baseline HIV RNA levels correlated with the development of protease mutations. Mutations at codon 215 were present in 82% of all patients at baseline and in 87% after therap

Implementing Loss Distribution Approach for Operational Risk

To quantify the operational risk capital charge under the current regulatory framework for banking supervision, referred to as Basel II, many banks adopt the Loss Distribution Approach. There are many modeling issues that should be resolved to use the approach in practice. In this paper we review the quantitative methods suggested in literature for implementation of the approach. In particular, the use of the Bayesian inference method that allows to take expert judgement and parameter uncertainty into account, modeling dependence and inclusion of insurance are discussed

The Factory and The Beehive I. Rotation Periods For Low-Mass Stars in Praesepe

Stellar rotation periods measured from single-age populations are critical for investigating how stellar angular momentum content evolves over time, how that evolution depends on mass, and how rotation influences the stellar dynamo and the magnetically heated chromosphere and corona. We report rotation periods for 40 late-K to mid-M stars members of the nearby, rich, intermediate-age (~600 Myr) open cluster Praesepe. These rotation periods were derived from ~200 observations taken by the Palomar Transient Factory of four cluster fields from 2010 February to May. Our measurements indicate that Praesepe's mass-period relation transitions from a well-defined singular relation to a more scattered distribution of both fast and slow rotators at ~0.6 Msun. The location of this transition is broadly consistent with expectations based on observations of younger clusters and the assumption that stellar-spin down is the dominant mechanism influencing angular momentum evolution at 600 Myr. However, a comparison to data recently published for the Hyades, assumed to be coeval to Praesepe, indicates that the divergence from a singular mass-period relation occurs at different characteristic masses, strengthening the finding that Praesepe is the younger of the two clusters. We also use previously published relations describing the evolution of rotation periods as a function of color and mass to evolve the sample of Praesepe periods in time. Comparing the resulting predictions to periods measured in M35 and NGC 2516 (~150 Myr) and for kinematically selected young and old field star populations suggests that stellar spin-down may progress more slowly than described by these relations.Comment: To appear in the ApJ. 18 pages, 12 figures; version with higher resolution figures available at http://www.astro.columbia.edu/~marcel/papers/praesepe.pdf. Paper title inspired by local news; see http://tinyurl.com/redhone

A Simple Iterative Algorithm for Parsimonious Binary Kernel Fisher Discrimination

By applying recent results in optimization theory variously known as optimization transfer or majorize/minimize algorithms, an algorithm for binary, kernel, Fisher discriminant analysis is introduced that makes use of a non-smooth penalty on the coefficients to provide a parsimonious solution. The problem is converted into a smooth optimization that can be solved iteratively with no greater overhead than iteratively re-weighted least-squares. The result is simple, easily programmed and is shown to perform, in terms of both accuracy and parsimony, as well as or better than a number of leading machine learning algorithms on two well-studied and substantial benchmarks