Shape restricted regression with random Bernstein polynomials

Shape restricted regressions, including isotonic regression and concave regression as special cases, are studied using priors on Bernstein polynomials and Markov chain Monte Carlo methods. These priors have large supports, select only smooth functions, can easily incorporate geometric information into the prior, and can be generated without computational difficulty. Algorithms generating priors and posteriors are proposed, and simulation studies are conducted to illustrate the performance of this approach. Comparisons with the density-regression method of Dette et al. (2006) are included.Comment: Published at http://dx.doi.org/10.1214/074921707000000157 in the IMS Lecture Notes Monograph Series (http://www.imstat.org/publications/lecnotes.htm) by the Institute of Mathematical Statistics (http://www.imstat.org

Profiling time course expression of virus genes---an illustration of Bayesian inference under shape restrictions

There have been several studies of the genome-wide temporal transcriptional program of viruses, based on microarray experiments, which are generally useful in the construction of gene regulation network. It seems that biological interpretations in these studies are directly based on the normalized data and some crude statistics, which provide rough estimates of limited features of the profile and may incur biases. This paper introduces a hierarchical Bayesian shape restricted regression method for making inference on the time course expression of virus genes. Estimates of many salient features of the expression profile like onset time, inflection point, maximum value, time to maximum value, area under curve, etc. can be obtained immediately by this method. Applying this method to a baculovirus microarray time course expression data set, we indicate that many biological questions can be formulated quantitatively and we are able to offer insights into the baculovirus biology.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS258 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

A Bayesian measurement error model for two-channel cell-based RNAi data with replicates

RNA interference (RNAi) is an endogenous cellular process in which small double-stranded RNAs lead to the destruction of mRNAs with complementary nucleoside sequence. With the production of RNAi libraries, large-scale RNAi screening in human cells can be conducted to identify unknown genes involved in a biological pathway. One challenge researchers face is how to deal with the multiple testing issue and the related false positive rate (FDR) and false negative rate (FNR). This paper proposes a Bayesian hierarchical measurement error model for the analysis of data from a two-channel RNAi high-throughput experiment with replicates, in which both the activity of a particular biological pathway and cell viability are monitored and the goal is to identify short hair-pin RNAs (shRNAs) that affect the pathway activity without affecting cell activity. Simulation studies demonstrate the flexibility and robustness of the Bayesian method and the benefits of having replicates in the experiment. This method is illustrated through analyzing the data from a RNAi high-throughput screening that searches for cellular factors affecting HCV replication without affecting cell viability; comparisons of the results from this HCV study and some of those reported in the literature are included.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS496 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

ESTIMATION IN A PROPORTIONAL HAZARD MODEL FOR SEMI-MARKOV COUNTING PROCESS

Abstract: Estimation is studied in a regression model for counting processes whose baseline intensity processes are of semi-Markov form. Asymptotic normality is established for a Breslow-type estimator of the cumulative baseline hazard for each gap time of the counting process

UPS 2.0: unique probe selector for probe design and oligonucleotide microarrays at the pangenomic/ genomic level

<p>Abstract</p> <p>Background</p> <p>Nucleic acid hybridization is an extensively adopted principle in biomedical research, in which the performance of any hybridization-based method depends on the specificity of probes to their targets. To determine the optimal probe(s) for detecting target(s) from a sample cocktail, we developed a novel algorithm, which has been implemented into a web platform for probe designing. This probe design workflow is now upgraded to satisfy experiments that require a probe designing tool to take the increasing volume of sequence datasets.</p> <p>Results</p> <p>Algorithms and probe parameters applied in UPS 2.0 include GC content, the secondary structure, melting temperature (Tm), the stability of the probe-target duplex estimated by the thermodynamic model, sequence complexity, similarity of probes to non-target sequences, and other empirical parameters used in the laboratory. Several probe background options,<b><it>Unique probe within a group</it></b><it>,</it><b><it>Unique probe in a specific Unigene set</it></b><it>,</it><b><it>Unique probe based onthe pangenomic level</it></b><it>,</it> and <b><it>Unique Probe in the user-defined genome/transcriptome</it></b><it>,</it> are available to meet the scenarios that the experiments will be conducted. Parameters, such as salt concentration and the lower-bound Tm of probes, are available for users to optimize their probe design query. Output files are available for download on the result page. Probes designed by the UPS algorithm are suitable for generating microarrays, and the performance of UPS-designed probes has been validated by experiments.</p> <p>Conclusions</p> <p>The UPS 2.0 evaluates probe-to-target hybridization under a user-defined condition to ensure high-performance hybridization with minimal chance of non-specific binding at the pangenomic and genomic levels. The UPS algorithm mimics the target/non-target mixture in an experiment and is very useful in developing diagnostic kits and microarrays. The UPS 2.0 website has had more than 1,300 visits and 360,000 sequences performed the probe designing task in the last 30 months. It is freely accessible at <url>http://array.iis.sinica.edu.tw/ups/.</url></p> <p>Screen cast: <url>http://array.iis.sinica.edu.tw/ups/demo/demo.htm</url></p

POWER: PhylOgenetic WEb Repeater—an integrated and user-optimized framework for biomolecular phylogenetic analysis

POWER, the PhylOgenetic WEb Repeater, is a web-based service designed to perform user-friendly pipeline phylogenetic analysis. POWER uses an open-source LAMP structure and infers genetic distances and phylogenetic relationships using well-established algorithms (ClustalW and PHYLIP). POWER incorporates a novel tree builder based on the GD library to generate a high-quality tree topology according to the calculated result. POWER accepts either raw sequences in FASTA format or user-uploaded alignment output files. Through a user-friendly web interface, users can sketch a tree effortlessly in multiple steps. After a tree has been generated, users can freely set and modify parameters, select tree building algorithms, refine sequence alignments or edit the tree topology. All the information related to input sequences and the processing history is logged and downloadable for the user's reference. Furthermore, iterative tree construction can be performed by adding sequences to, or removing them from, a previously submitted job. POWER is accessible at

ATIVS: analytical tool for influenza virus surveillance

The WHO Global Influenza Surveillance Network has routinely performed genetic and antigenic analyses of human influenza viruses to monitor influenza activity. Although these analyses provide supporting data for the selection of vaccine strains, it seems desirable to have user-friendly tools to visualize the antigenic evolution of influenza viruses for the purpose of surveillance. To meet this need, we have developed a web server, ATIVS (Analytical Tool for Influenza Virus Surveillance), for analyzing serological data of all influenza viruses and hemagglutinin sequence data of human influenza A/H3N2 viruses so as to generate antigenic maps for influenza surveillance and vaccine strain selection. Functionalities are described and examples are provided to illustrate its usefulness and performance. The ATIVS web server is available at http://influenza.nhri.org.tw/ATIVS/

Novel G9 rotavirus strains co-circulate in children and pigs, Taiwan

Molecular epidemiologic studies collecting information of the spatiotemporal distribution of rotavirus VP7 (G) and VP4 (P) genotypes have shown evidence for the increasing global importance of genotype G9 rotaviruses in humans and pigs. Sequence comparison of the VP7 gene of G9 strains identified different lineages to prevail in the respective host species although some of these lineages appear to be shared among heterologous hosts providing evidence of interspecies transmission events. The majority of these events indicates the pig-to-human spillover, although a reverse route of transmission cannot be excluded either. In this study, new variants of G9 rotaviruses were identified in two children with diarrhea and numerous pigs in Taiwan. Whole genome sequence and phylogenetic analyses of selected strains showed close genetic relationship among porcine and human strains suggesting zoonotic origin of Taiwanese human G9 strains detected in 2014–2015. Although the identified human G9P[19] and G9P[13] rotaviruses represented minority strains, the repeated detection of porcine-like rotavirus strains in Taiwanese children over time justifies the continuation of synchronized strain surveillance in humans and domestic animals