Exploiting the full power of temporal gene expression profiling through a new statistical test: Application to the analysis of muscular dystrophy data

Background: The identification of biologically interesting genes in a temporal expression profiling dataset is challenging and complicated by high levels of experimental noise. Most statistical methods used in the literature do not fully exploit the temporal ordering in the dataset and are not suited to the case where temporal profiles are measured for a number of different biological conditions. We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T2-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other. Results: We validate the temporal Hotelling T2-test on muscular gene expression data from four mouse strains which were profiled at different ages: dystrophin-, beta-sarcoglycan and gammasarcoglycan deficient mice, and wild-type mice. The first three are animal models for different muscular dystrophies. Extensive biological validation shows that the method is capable of finding genes with temporal profiles significantly different across the four strains, as well as identifying potential biomarkers for each form of the disease. The added value of the temporal test compared to an identical test which does not make use of temporal ordering is demonstrated via a simulation study, and through confirmation of the expression profiles from selected genes by quantitative PCR experiments. The proposed method maximises the detection of the biologically interesting genes, whilst minimising false detections. Conclusion: The temporal Hotelling T2-test is capable of finding relatively small and robust sets of genes that display different temporal profiles between the conditions of interest. The test is simple, it can be used on gene expression data generated from any experimental design and for any number of conditions, and it allows fast interpretation of the temporal behaviour of genes. The R code is available from V.V. The microarray data have been submitted to GEO under series GSE1574 and GSE3523

A parallel framework for in-memory construction of term-partitioned inverted indexes

Cataloged from PDF version of article.With the advances in cloud computing and huge RAMs provided by 64-bit architectures, it is possible to tackle large problems using memory-based solutions. Construction of term-based, partitioned, parallel inverted indexes is a communication intensive task and suitable for memory-based modeling. In this paper, we provide an efficient parallel framework for in-memory construction of term-based partitioned, inverted indexes. We show that, by utilizing an efficient bucketing scheme, we can eliminate the need for the generation of a global vocabulary. We propose and investigate assignment schemes that can reduce the communication overheads while minimizing the storage and final query processing imbalance. We also present a study on how communication among processors should be carried out with limited communication memory in order to reduce the total inversion time. We present several different communication-memory organizations and discuss their advantages and shortcomings. The conducted experiments indicate promising results. © 2012 The Author. Published by Oxford University Press on behalf of The British Computer Society

New Perspectives on the Role of Vitiligo in Immune Responses to Melanoma

Melanoma-associated vitiligo is the best-studied example of the linkage between tumor immunity and autoimmunity. Although vitiligo is an independent positive prognostic factor for melanoma patients, the autoimmune destruction of melanocytes was long thought to be merely a side effect of robust anti-tumor immunity. However, new data reveal a key role for vitiligo in supporting T cell responses to melanoma. This research perspective reviews the history of melanoma-associated vitiligo in patients, the experimental studies that form the basis for understanding this relationship, and the unique characteristics of melanoma-specific CD8 T cells found in hosts with vitiligo. We also discuss the implications of our recent findings for the interpretation of patient responses, and the design of next-generation cancer immunotherapies

Isolation of Cathepsin Band a-N-Benzoylarginine-B-naphthylamide Hydrolase by Covalent Chromatography on Activated Thiol Sepharose

Cathepsin Band a-N-benzoylarginine-P,-naphthylamide (BANA) hydrolase have been isolated from bovine lymph nodes using a novel procedure that includes besides gel filtration and ion exchange chromatography also covalent chromatography as the essential step. Both enzymes were selectively bound to the activated thiol-Sepharose and afterwards eluted with cysteine. The homogeneity of enzymes was proved by polyacrylamide gel electrophoresis

The Birth of a Galaxy - III. Propelling reionisation with the faintest galaxies

Starlight from galaxies plays a pivotal role throughout the process of cosmic reionisation. We present the statistics of dwarf galaxy properties at z > 7 in haloes with masses up to 10^9 solar masses, using a cosmological radiation hydrodynamics simulation that follows their buildup starting with their Population III progenitors. We find that metal-enriched star formation is not restricted to atomic cooling ($T_{\rm vir} \ge 10^4$ K) haloes, but can occur in haloes down to masses ~10^6 solar masses, especially in neutral regions. Even though these smallest galaxies only host up to 10^4 solar masses of stars, they provide nearly 30 per cent of the ionising photon budget. We find that the galaxy luminosity function flattens above M_UV ~ -12 with a number density that is unchanged at z < 10. The fraction of ionising radiation escaping into the intergalactic medium is inversely dependent on halo mass, decreasing from 50 to 5 per cent in the mass range $\log M/M_\odot = 7.0-8.5$. Using our galaxy statistics in a semi-analytic reionisation model, we find a Thomson scattering optical depth consistent with the latest Planck results, while still being consistent with the UV emissivity constraints provided by Ly$\alpha$ forest observations at z = 4-6.Comment: 21 pages, 15 figures, 4 tables. Accepted in MNRA