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Type Package Package ORIClust February 19, 2015 Title Order-restricted Information Criterion-based Clustering Algorithm Version 1.0-1 Date 2009-09-10 Author Maintainer Tianqing Liu <tianqingliu@gmail.com> ORIClust is a user-friendly R-based software package for gene clustering. Clusters are given by genes matched to prespecified profiles across various ordered treatment groups. It is particularly useful for analyzing obtained from short time-course or dose-response microarray experiments. License GPL-2 LazyLoad yes Repository CRAN Date/Publication 2012-10-29 08:57:22 NeedsCompilation no R topics documented: ORIClust-package...................................... 2 Breast............................................ 2 complete.profile....................................... 3 cyclical.max.min...................................... 4 cyclical.min.max...................................... 5 decreasing.......................................... 6 down.up........................................... 7 flat.pattern.......................................... 8 increasing.......................................... 9 isodecre........................................... 10 isoincre........................................... 11 ORICC1........................................... 12 1

2 Breast ORICC2........................................... 14 up.down........................................... 16 Index 18 ORIClust-package Order-restricted Information Criterion-based Clustering Algorithm Details ORIClust is a user-friendly R-based software package for gene clustering. Clusters are given by genes matched to prespecified profiles across various ordered treatment groups. It is particularly useful for analyzing obtained from short time-course or dose-response microarray experiments. Package: ORIClust Type: Package Version: 1.0 Date: 2009-05-24 License: GPL-2 LazyLoad: yes The main functions are ORICC1 and ORICC2, see the documentation files with examples. candidate profiles in short time-course microarray experiments, BMC Bioinformatics, 10: 146. Breast Breast cancer cell line This set comes from a breast cancer cell line microarray study. The experiment was done as follows. First, the MCF-7 breast cancer cell line was treated with 17 beta-estradiol or ethanol (vehicle control). Then, samples were harvested at 1, 4, 12, 24, 36 and 48 hours after treatment. At each time point, M = 8 replicate arrays were prepared with each array consisting of G = 1901 genes.

complete.profile 3 Breast Format A matrix containing 1901 rows and 50 columns. Lobenhofer, E., Bennett, L., Cable, P., Li, L., Bushel, P., and Afshari, C. (2002), Regulation of DNA replication fork genes by 17 beta-estradiol. Molec. Endocrin., 16, 1215-1229. complete.profile complete.profile Returns the log-maximum likelihood and the estimator of the mean when there is no inequality constraint. complete.profile(,x,) x A vector containing the expressions of one gene. where logelr mu Log-maximum likelihood Maintainer:Tianqing Liu <tianqingliu@gmail.com>

4 cyclical.max.min cyclical.max.min cyclical.max.min Returns the log-maximum likelihood and the estimator of the mean under cyclical profile with maximum at max1 and minimum at min1 (max1 < min1). cyclical.max.min(,x,,max1,min1) x max1 min1 A vector containing the expressions of one gene. where Cyclical profile with maximum at max1. Cyclical profile with minimum at min1. logelr mu Log-maximum likelihood Robertson, T., Wright, F. T. and Dykstra, R. L. (1988). Order restricted statistical inference. New York: Wiley. Shi, N., Gao, W. and Zhang, B. (2001). One sided estimation and testing problems for location models from grouped samples. Commun Statist-Simula, 30: 885-898.

cyclical.min.max 5 cyclical.min.max cyclical.min.max Returns the log-maximum likelihood and the estimator of the mean under cyclical profile with minimum at min1 and maximum at max1 (min1 < max1). cyclical.min.max(,x,,min1,max1) x min1 max1 A vector containing the expressions of one gene. where Cyclical profile with minimum at min1 cyclical profile with maximum at max1 logelr mu Log-maximum likelihood Robertson, T., Wright, F. T. and Dykstra, R. L. (1988). Order restricted statistical inference. New York: Wiley. Shi, N., Gao, W. and Zhang, B. (2001). One sided estimation and testing problems for location models from grouped samples. Commun Statist-Simula, 30: 885-898.

6 decreasing decreasing decreasing Returns the log-maximum likelihood and the estimator of the mean under the monotone decreasing profile. decreasing(,x,) x A vector containing the expressions of one gene. where logelr mu Log-maximum likelihood Robertson, T., Wright, F. T. and Dykstra, R. L. (1988). Order restricted statistical inference. New York: Wiley. Shi, N., Gao, W. and Zhang, B. (2001). One sided estimation and testing problems for location models from grouped samples. Commun Statist-Simula, 30: 885-898.

down.up 7 down.up down.up Returns the log-maximum likelihood and the estimator of the mean under down-up profile with minimum at h. down.up(,x,,h) x A vector containing the expressions of one gene. where h Down-up profile with minimum at h. logelr mu Log-maximum likelihood Robertson, T., Wright, F. T. and Dykstra, R. L. (1988). Order restricted statistical inference. New York: Wiley. Shi, N., Gao, W. and Zhang, B. (2001). One sided estimation and testing problems for location models from grouped samples. Commun Statist-Simula, 30: 885-898.

8 flat.pattern flat.pattern flat.pattern Returns the log-maximum likelihood and the estimator of the mean under the equality constraint that all means are equal. flat.pattern(,x,) x A vector containing the expressions of one gene. where logelr mu Log-maximum likelihood Robertson, T., Wright, F. T. and Dykstra, R. L. (1988). Order restricted statistical inference. New York: Wiley. Shi, N., Gao, W. and Zhang, B. (2001). One sided estimation and testing problems for location models from grouped samples. Commun Statist-Simula, 30: 885-898.

increasing 9 increasing increasing Returns the log-maximum likelihood and the estimator of the mean under the monotone increasing profile. increasing(,x,) x A vector containing the expressions of one gene. where logelr mu Log-maximum likelihood Robertson, T., Wright, F. T. and Dykstra, R. L. (1988). Order restricted statistical inference. New York: Wiley. Shi, N., Gao, W. and Zhang, B. (2001). One sided estimation and testing problems for location models from grouped samples. Commun Statist-Simula, 30: 885-898.

10 isodecre isodecre isodecre Isotonic regression of a with weights w under monotone decreasing profile. isodecre(a, w) a w The weights. is Robertson, T., Wright, F. T. and Dykstra, R. L. (1988). Order restricted statistical inference. New York: Wiley. Shi, N., Gao, W. and Zhang, B. (2001). One sided estimation and testing problems for location models from grouped samples. Commun Statist-Simula, 30: 885-898.

isoincre 11 isoincre isoincre Isotonic regression of a with weights w under monotone increasing profile. isoincre(a, w) a w The weights. is Robertson, T., Wright, F. T. and Dykstra, R. L. (1988). Order restricted statistical inference. New York: Wiley. Shi, N., Gao, W. and Zhang, B. (2001). One sided estimation and testing problems for location models from grouped samples. Commun Statist-Simula, 30: 885-898.

12 ORICC1 ORICC1 One-stage ORICC One-stage ORICC is a computationally efficient information criterion-based clustering algorithm for selecting and clustering genes according to their time-course or dose-response profiles. This algorithm takes account of the ordering in time-course or dose-response experiments by embedding the order-restricted inference into a model selection framework. This algorithm mainly consist of two steps. In the first step, candidate profiles are defined in terms of inequalities among mean expression levels at different time points or doses levels. In the second step, genes are assigned to the best matched profiles determined by an information criterion for order-restricted inference. ORICC1(,.col,id.col,,n.top,transform, name.profile,cyclical.profile,complete.profile, onefile,plot.format).col A matrix containing the gene expressions. Column indices of the gene expression. id.col Column index of the gene ID. Defaults to 1. n.top transform name.profile where The number of genes kept for the final clustering result. Genes are ranked based on expression variation across time or dose levels. Defaults to all genes ORICC1 selects Transformation of the original : 0=None, 1=natural log, 2=square root, 3=cubic root. Defaults to 0. A character string specifying the collection of candidate profiles. This option only supports monotone, up-down and down-up profiles specified as by "decreasing"; "increasing". paste("up down max at",i,sep=" "); paste("down up min at",j,sep=" "); If name.profile="all", the decreasing, increasing and all up-down and down-up profiles will be included. If name.profile=null, decreasing, increasing and all up-down and downup profiles will be absent. Defaults to NULL. One can also specify several up-down or down-up profiles together as follows.

ORICC1 13 profile1=paste("up down max at",c(2,4),sep=" "); profile2=paste("down up min at",c(3,5),sep=" "); name.profile=c(profile1,profile2); then up-down profile with maxima at 2 and 4 as well as down-up profile with minima at 3 and 5 will be included. cyclical.profile A matrix with 2 columns. Each element of the matrix must be a number in the set {2,3,...,T-1}. Each row of the matrix represents a cyclical profile with minima at the first entry of the row and maxima at the 2nd entry. As a result, two elements in the same row must be different. For example, if cyclical.profile=matrix(c(2,3,4,3),2,2,byrow=t), then the cyclical profile with minima at 2 and maxima at 3 and the cyclical profile with minima at 4 and maxima at 3 will be included as candidate profiles. If cyclical.profile=null, all cyclical profiles will be absent. Defaults to NULL. complete.profile The complete.profile means a profile in which there is no defined inequality constraint. onefile plot.format If the complete.profile is a candidate profile, complete.profile=1, otherwise, complete.profile=null. Defaults to NULL. logical: if true (the default) multiple figures for different clusters are output in one file. If FALSE, each cluster is plotted in a seperate file. Defaults to TRUE. The format of the output file containing plots of gene clusters.users can choose between eps and jpg. Defaults to eps. Details The gene expression set should be in a tab-delimited txt file, in which the first two columns contain the gene names and their accession numbers or descriptions, and the remaining columns, in their orders, are the geneexpression (contain multiple columns, i.e..col).the set is assumed to have been processed so that each row contains the expressions of only one gene. The results are displayed in a graphical form. The graphics can be stored in a JPG or EPS format. Both the raw gene expression values and the estimated mean expressions are output to external files cluster of raw.txt and cluster of fitted mean.txt, respectively.

14 ORICC2 Examples (Breast) ORICC1(Breast,.col=3:50,id.col=1,=rep(8,6), n.top=50,transform=1,name.profile="all",plot.format="eps") ORICC2 Two-stage ORICC It is a computationally efficient two-stage algorithm by adding a pre-screening stage. It first screens out genes that show no significant changes over time, and then applies the one-stage algorithm to a much smaller set of remained genes. ORICC2(,.col,id.col,,n.top,transform, name.profile,cyclical.profile, onefile,plot.format).col A matrix containing the gene expressions. Column indices of the gene expression. id.col Column index of the gene ID. Defaults to 1. n.top transform name.profile where The number of genes kept for the final clustering result. Genes are ranked based on expression variation across time or dose levels. Defaults to all genes ORICC2 selects Transformation of the original : 0=None, 1=natural log, 2=square root, 3=cubic root. Defaults to 0. A character string specifying the collection of candidate profiles. This option only supports monotone, up-down and down-up profiles specified as by "decreasing"; "increasing". paste("up down max at",i,sep=" ");

ORICC2 15 paste("down up min at",j,sep=" "); If name.profile="all", the decreasing, increasing and all up-down and down-up profiles will be included. If name.profile=null, decreasing, increasing and all up-down and downup profiles will be absent. Defaults to NULL. One can also specify several up-down or down-up profiles together as follows. profile1=paste("up down max at",c(2,4),sep=" "); profile2=paste("down up min at",c(3,5),sep=" "); name.profile=c(profile1,profile2); then up-down profile with maxima at 2 and 4 as well as down-up profile with minima at 3 and 5 will be included. cyclical.profile A matrix with 2 columns. Each element of the matrix must be a number in the set {2,3,...,T-1 }. Each row of the matrix represents a cyclical profile with minima at the first entry of the row and maxima at the 2nd entry. As a result, two elements in the same row must be different. For example, if onefile plot.format cyclical.profile=matrix(c(2,3,4,3),2,2,byrow=t), then the cyclical profile with minima at 2 and maxima at 3 and the cyclical profile with minima at 4 and maxima at 3 will be included as candidate profiles. If cyclical.profile=null, all cyclical profiles will be absent. Defaults to NULL. logical: if true (the default) multiple figures for different clusters are output in one file. If FALSE, each cluster is plotted in a seperate file. Defaults to TRUE. The format of the output file containing plots of gene clusters.users can choose between eps and jpg. Defaults to eps. Details The gene expression set should be in a tab-delimited txt file, in which the first two columns contain the gene names and their accession numbers or descriptions, and the remaining columns, in their orders, are the geneexpression (contain multiple columns, i.e..col).the set is assumed to have been processed so that each row contains the expressions of only one gene. The results are displayed in a graphical form. The graphics can be stored in a JPG or EPS format. Both the raw gene expression values and the estimated mean expressions are output to external files cluster of raw.txt and cluster of fitted mean.txt, respectively.

16 up.down Examples (Breast) ORICC2(Breast,.col=3:50,id.col=1,=rep(8,6), n.top=50,transform=1,name.profile="all",plot.format="eps") up.down up.down Returns the log-maximum likelihood and the estimator of the mean under under up-down profile with maximum at h. up.down(,x,,h) x A vector containing the expressions of one gene. where h Up-down profile with maximum at h. logelr mu Log-maximum likelihood

up.down 17 Robertson, T., Wright, F. T. and Dykstra, R. L. (1988). Order restricted statistical inference. New York: Wiley. Shi, N., Gao, W. and Zhang, B. (2001). One sided estimation and testing problems for location models from grouped samples. Commun Statist-Simula, 30: 885-898.

Index Topic sets Breast, 2 Topic package complete.profile, 3 cyclical.max.min, 4 cyclical.min.max, 5 decreasing, 6 down.up, 7 flat.pattern, 8 increasing, 9 isodecre, 10 isoincre, 11 ORICC1, 12 ORICC2, 14 ORIClust-package, 2 up.down, 16 Breast, 2 complete.profile, 3 cyclical.max.min, 4 cyclical.min.max, 5 decreasing, 6 down.up, 7 flat.pattern, 8 increasing, 9 isodecre, 10 isoincre, 11 ORICC1, 2, 12 ORICC2, 2, 14 ORIClust-package, 2 up.down, 16 18