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Type Package Title LiquidAssociation Version 1.36.0 Date 2009-10-07 Package LiquidAssociation Author Yen-Yi Ho <yho@jhsph.edu> Maintainer Yen-Yi Ho <yho@jhsph.edu> March 8, 2019 The package contains functions for calculate direct and model-based estimators for liquid association. It also provides functions for testing the existence of liquid association given a gene triplet data. Depends geepack, methods, yeastcc, org.sc.sgd.db Imports Biobase, graphics, grdevices, methods, stats License GPL (>=3) LazyLoad yes biocviews Pathways, GeneExpression, CellBiology, Genetics, Network, TimeCourse git_url https://git.bioconductor.org/packages/liquidassociation git_branch RELEASE_3_8 git_last_commit ceead18 git_last_commit_date 2018-10-30 Date/Publication 2019-03-07 R topics documented: LiquidAssociation-package................................. 2 CNM-class......................................... 3 CNM.full-methods..................................... 4 CNM.simple-methods.................................... 5 getsgla-methods...................................... 6 getsla-methods....................................... 7 GLA-methods........................................ 8 LA-methods......................................... 9 plotgla-methods...................................... 10 Index 12 1

2 LiquidAssociation-package LiquidAssociation-package Liquid Associaiton Package The LiquidAssociation package provide methods to examine a special kind of three-way interaction called liquid association. The term liquid association was first proposed by contains functions for calculate direct and model-based estimators for liquid associaiton. It also provides functions for testing the existence of liquid associaiton given a gene triplet data. Package: LiquidAssociation Type: Package Version: 1.0.4 Date: 2009-10-05 License: GPL version 2 or newer LazyLoad: yes GLA LA CNM.full CNM.simple getsgla getsla plotgla Yen-Yi Ho <yho@jhsph.edu> Maintainer: Yen-Yi Ho <yho@jhsph.edu> Ker-Chau Li, Genome-wide coexpression dynamics: theory and application (2002). PNAS 99 (26): 16875-16880. Working Paper 183. http://www.bepress.com/jhubiostat/paper183 FitCNM.full<-CNM.full(data) FitCNM.full

CNM-class 3 CNM-class Class CNM This is a class representation for CNM model fitting results. Objects from the Class Objects can be created by calls of the form new("cnm",...) or the functions CNM.full-methods and CNM.simple-methods Slots Model: Object of class character representing the fitted CNM model. output: Object of class matrix representing the parameter estimates from the fitted CNM model. Methods print signature(x = "CNM"): Display CNM model fitting result. show signature( = "CNM"): Display CNM model fitting result. Note The usage of this class is demonstrated in the vignette. Yen-Yi Ho Working Paper 183. http://www.bepress.com/jhubiostat/paper183. Yen-Yi Ho, Leslie Cope, Thomas A. Louis, and Giovanni Parmigiani, GENERALIZED LIQUID ASSOCIATION (April 2009). Johns Hopkins University, Dept. of Biostatistics Working Papers. Working Paper 183. http://www.bepress.com/jhubiostat/paper183. related methods print, show. showclass("cnm")

4 CNM.full-methods CNM.full-methods The function fits a full conditional normal model (CNM) CNM.full is used to fit the full (means, variance, and correlation) conditional normal model using GEE. An numerical matrix with three columns or an of ExpressionSet class with three features. The default value is =3. Value The input can be a numerical matrix with three columns with row representing observations and column representing three variables. It can also be an ExpressionSet with three features. If input a matrix class data, all three columns of the representing the variables should have column names. Each variable in the will be standardized with mean 0 and variance 1 in the function. In addition, the third variable will be quantile normalized within the function. More detail example about the usage of is demonstrated in the vignette. CNM.full returns a of CNM class with two Slots. The first slot describes the fitted model. The second slot is a matrix contains the CNM model fitting results. The row of this matrix represents the parameters in the CNM model. The first column, estimates, is the estimated value of the corresponding parameters. The second column, san.se, is the value of sandwich standard error estimator for the estimates. The third column, wald, is the wald test statistic as described in Ho et al (2009). The corresponding p value for the wald test statistic is represented in the fourth column. A more detailed interpretation of these values is illustrated in the vignette. Yen-Yi Ho Working Paper 183. http://www.bepress.com/jhubiostat/paper183. Jun Yan and Jason Fine. Estimating equations for association structures Statistics in Medicine. 23(6): 859 74; discussion 875-7,879-80. http://dx.doi.org/10.1002/sim.1650 CNM.simple-methods, CNM-class

CNM.simple-methods 5 FitCNM.full<-CNM.full(data) FitCNM.full CNM.simple-methods The function fits a reduced conditional normal model (CNM) CNM.simple is used to fit the reduced (correlation only) conditional normal model using GEE. An numerical matrix with three columns or an of ExpressionSet class with three features. The default value is =3. The input can be a numerical matrix with three columns with row representing observations and column representing three variables. It can also be an ExpressionSet with three features. If input a matrix class data, all three columns of the representing the variables should have column names. Each variable in the will be standardized with mean 0 and variance 1 in the function. In addition, the third variable will be quantile normalized within the function. More detail example about the usage of is demonstrated in the vignette. Value CNM.full returns a of CNM class with two Slots. The first slot describes the fitted model. The second slot is a matrix contains the CNM model fitting results. The row of this matrix represents the parameters in the CNM model. The first column, estimates, is the estimated value of the corresponding parameters. The second column, san.se, is the value of sandwich standard error estimator for the estimates. The third column, wald, is the wald test statistic as described in Ho et al (2009). The corresponding p value for the wald test statistic is represented in the fourth column. A more detailed interpretation of these values is illustrated in the vignette. Yen-Yi Ho

6 getsgla-methods Working Paper 183. http://www.bepress.com/jhubiostat/paper183. Jun Yan and Jason Fine. Estimating equations for association structures Statistics in Medicine. 23(6): 859 74; discussion 875-7,879-80. http://dx.doi.org/10.1002/sim.1650 CNM.full-methods, CNM-class FitCNM.simple<-CNM.simple(data) FitCNM.simple getsgla-methods Function to calculate the sgla test statistic for a given triplet data getsgla is used to calculate the sgla test statistic and correponding p value. boots perm cut An numerical matrix with three columns or an of ExpresionSet class with three features. The number of bootstrap iterations for estimating the bootstrap standard error of sgla. Default value is boots=30. The number of permutation iterations for generating the null distribution of the sgla test statistic. Default is perm=100. cut==m +1. M is the number of grip points pre-specifed over the third variable. Default is =3

getsla-methods 7 The input can be a numerical matrix with three columns with row representing observations and column representing three variables. It can also be an ExpressionSet with three features. If input a matrix class data, all three columns of the representing the variables should have column names. Each variable in the will be standardized with mean 0 and variance 1 in the function. In addition, the third variable will be quantile normalized within the function. More detail example about the usage of is demonstrated in the vignette. Value getsgla returns a vector with two elements. The first element is the value of test statistic and second element is the corresponding p value. A more detailed interpretation of these values is illustrated in the vignette. Working Paper 183. http://www.bepress.com/jhubiostat/paper183. GLA-methods, getsla-methods sglaest<-getsgla(data, boots=20, perm=100, cut=4, =3) sglaest getsla-methods Function to calculate the sla test statistic for a given triplet data getsla is used to calculate the sla test statistic and correponding p value. boots perm An numerical matrix with three columns or an of ExpresionSet class with three features. The number of bootstrap iterations for estimating the bootstrap standard error of sgla. Default value is boots=30. The number of permutation iterations for generating the null distribution of the sgla test statistic. Default is perm=100.

8 GLA-methods Default is =3 Value The input can be a numerical matrix with three columns with row representing observations and column representing three variables. It can also be an ExpressionSet with three features. If input a matrix class data, all three columns of the representing the variables should have column names. Each variable in the will be standardized with mean 0 and variance 1 in the function. In addition, the third variable will be quantile normalized within the function. More detail example about the usage of is demonstrated in the vignette. getsla returns a vector with two elements. The first element is the value of test statistic and second element is the corresponding p value. A more detailed interpretation of these values is illustrated in the vignette. LA, getsgla slaest<-getsla(data, boots=20, perm=100) slaest GLA-methods Function to calculate GLA estimate GLA is used to calculate the GLA estimate for a gene triplet data. cut An numerical matrix with three columns or an of ExpresionSet class with three features. cut==m +1. M is the number of grip points pre-specifed over the third variable. Default is =3

LA-methods 9 The input can be a numerical matrix with three columns with row representing observations and column representing three variables. It can also be an ExpressionSet with three features. If input a matrix class data, all three columns of the representing the variables should have column names. Each variable in the will be standardized with mean 0 and variance 1 in the function. In addition, the third variable will be quantile normalized within the function. More detail example about the usage of is demonstrated in the vignette. Value GLA returns a numerical value representing the estimated value. A more detailed interpretation of the value is illustrated in the vignette. Yen-Yi Ho Working Paper 183. http://www.bepress.com/jhubiostat/paper183 LA-methods, getsgla-methods GLAest<-GLA(data, cut=4, =3) GLAest LA-methods Function to calculate LA estimate LA is used to calculate the LA estimate for a gene triplet data. An numerical matrix with three columns or an of ExpresionSet class with three features. Default is =3

10 plotgla-methods The input can be a numerical matrix with three columns with row representing observations and column representing three variables. It can also be an ExpressionSet with three features. If input a matrix class data, all three columns of the representing the variables should have column names. Each variable in the will be standardized with mean 0 and variance 1 in the function. In addition, the third variable will be quantile normalized within the function. More detail example about the usage of is demonstrated in the vignette. Value LA returns a numerical value representing the estimated value. A more detailed explanation of the value is illustrated in the vignette. Yen-Yi Ho Ker-Chau Li, Genome-wide coexpression dynamics: theory and application (2002). PNAS 99 (26): 16875-16880. Working Paper 183. http://www.bepress.com/jhubiostat/paper183 GLA-methods, getsla-methods LAest<-LA(data) LAest plotgla-methods The function plots scatter plots of two variables conditioning on the value of a third variable. plotgla is a function to plot the scatter plots of two variables conditioning on the value of a third variable.

plotgla-methods 11 cut filen save An numerical matrix with three columns or an of ExpresionSet class with three features.. cut==m +1. M is the number of grip points pre-specifed over the third variable. The file name for the output graph can be specified when save=true If save=true then output graphs will be save as PDF files with file name as specified by filen.... Other graphical parameters can be passed to function plot. The input can be a numerical matrix with three columns with row representing observations and column representing three variables. It can also be an ExpressionSet with three features. More detail example about the usage of is demonstrated in the vignette. Yen-Yi Ho Working Paper 183. http://www.bepress.com/jhubiostat/paper183 plotgla(data, cut=3, =3, pch=16, filen="glaplot", save=false)

Index Topic classes CNM-class, 3 Topic htest getsgla-methods, 6 getsla-methods, 7 Topic methods CNM.full-methods, 4 CNM.simple-methods, 5 getsgla-methods, 6 getsla-methods, 7 GLA-methods, 8 LA-methods, 9 plotgla-methods, 10 Topic models CNM.full-methods, 4 CNM.simple-methods, 5 Topic package LiquidAssociation-package, 2 CNM-class, 3 CNM.full (CNM.full-methods), 4 CNM.full,eSet-method (CNM.full-methods), 4 CNM.full,matrix-method (CNM.full-methods), 4 CNM.full-methods, 4 CNM.simple (CNM.simple-methods), 5 CNM.simple,eSet-method (CNM.simple-methods), 5 CNM.simple,matrix-method (CNM.simple-methods), 5 CNM.simple-methods, 5 GLA,matrix-method (GLA-methods), 8 GLA-methods, 8 LA (LA-methods), 9 LA,eSet-method (LA-methods), 9 LA,matrix-method (LA-methods), 9 LA-methods, 9 LiquidAssociation (LiquidAssociation-package), 2 LiquidAssociation-package, 2 plotgla (plotgla-methods), 10 plotgla,eset-method (plotgla-methods), 10 plotgla,matrix-method (plotgla-methods), 10 plotgla-methods, 10 print, 3 print,cnm-method (CNM-class), 3 show, 3 show,cnm-method (CNM-class), 3 getsgla (getsgla-methods), 6 getsgla,eset-method (getsgla-methods), 6 getsgla,matrix-method (getsgla-methods), 6 getsgla-methods, 6 getsla (getsla-methods), 7 getsla,eset-method (getsla-methods), 7 getsla,matrix-method (getsla-methods), 7 getsla-methods, 7 GLA (GLA-methods), 8 GLA,eSet-method (GLA-methods), 8 12