Package 'signatureSurvival'

Title: Signature Survival Analysis
Description: When multiple Cox proportional hazard models are performed on clinical data (month or year and status) and a set of differential expressions of genes, the results (Hazard risks, z-scores and p-values) can be used to create gene-expression signatures. Weights are calculated using the survival p-values of genes and are utilized to calculate expression values of the signature across the selected genes in all patients in a cohort. A Single or multiple univariate or multivariate Cox proportional hazard survival analyses of the patients in one cohort can be performed by using the gene-expression signature and visualized using our survival plots.
Authors: Yuan-De Tan [aut, cre] , Yuguang Ban [ctb]
Maintainer: Yuan-De Tan <[email protected]>
License: GPL (>= 3)
Version: 1.0.0
Built: 2025-03-11 04:01:22 UTC
Source: https://github.com/cran/signatureSurvival

Help Index


Signature Survival Analysis

Description

When multiple Cox proportional hazard models are performed on clinical data (month or year and status) and a set of differential expressions of genes, the results (Hazard risks, z-scores and p-values) can be used to create gene-expression signatures. Weights are calculated using the survival p-values of genes and are utilized to calculate expression values of the signature across the selected genes in all patients in a cohort. A Single or multiple univariate or multivariate Cox proportional hazard survival analyses of the patients in one cohort can be performed by using the gene-expression signature and visualized using our survival plots.

Details

The DESCRIPTION file:

Package: signatureSurvival
Type: Package
Title: Signature Survival Analysis
Version: 1.0.0
Date: 2023-07-17
Authors@R: c(person(given = "Yuan-De", family = "Tan", role = c("aut", "cre"), email = "[email protected]", comment = c(ORCID = "0000-0002-0364-2223")), person(given = "Yuguang", family = "Ban", role = "ctb"))
Maintainer: Yuan-De Tan <[email protected]>
Description: When multiple Cox proportional hazard models are performed on clinical data (month or year and status) and a set of differential expressions of genes, the results (Hazard risks, z-scores and p-values) can be used to create gene-expression signatures. Weights are calculated using the survival p-values of genes and are utilized to calculate expression values of the signature across the selected genes in all patients in a cohort. A Single or multiple univariate or multivariate Cox proportional hazard survival analyses of the patients in one cohort can be performed by using the gene-expression signature and visualized using our survival plots.
License: GPL (>= 3)
Depends: R(>= 3.5.0)
Imports: stats, utils,graphics,grDevices,dplyr,forestplot, gplots, gtools, survival,survminer,ggplot2
Suggests: Rmisc
LazyLoad: yes
NeedsCompilation: no
Encoding: UTF-8
LazyData: true
Packaged: 2023-07-18 13:18:21 UTC; yxt477
Author: Yuan-De Tan [aut, cre] (<https://orcid.org/0000-0002-0364-2223>), Yuguang Ban [ctb]
Date/Publication: 2023-07-19 11:10:02 UTC
Config/pak/sysreqs: cmake make libicu-dev libjpeg-dev libpng-dev libxml2-dev libssl-dev
Repository: https://yuande.r-universe.dev
RemoteUrl: https://github.com/cran/signatureSurvival
RemoteRef: HEAD
RemoteSha: 9fa077f4f7e95e571cee6afc8dbfedaf5f0b64ee

Index of help topics:

GSE50081                Survival data from cohort GSE50081
MKMplot                 Multivariate Kaplan-Meier survival curve plot
MMKMplot                Multiple multivariate Kaplan-Meier survival
                        curve plots
MUKMplot                Function multiple univariate Kaplan-Meier
                        survival curve plots
MVKMresult              Multivariate survival analysis with multiple
                        specified independent variables
SKMCresult              Univariate Cox proportional hazard survival
                        analysis with a specified independent variable
TCGA_forestplt          Data for forestplot
TCGA_survivalData       TCGA data for survival analysis
TS_signature            A signature constructed with a set of tumor
                        suppressor genes
UKMplot                 Univariate Kaplan-Meier survival curve plot
musvtest                Multiple univariate suvival tests with a set of
                        genes
mvstest                 Multivariate Cox proportional hazard survival
                        analyses with multiple genes
results                 results of univariate Cox proportional hazard
                        analysis of patients with ADC in three cohorts.
signatureExp            Signature expression or signature score
signatureSurvival-package
                        Signature Survival Analysis
signature_weight        Weights of genes in a signature
survivalForest          Forestplot for result of multivariate Cox
                        proportional hazard survival analysis
weight                  Caculation of Weights for signature genes

This package is used to create up and down signatures,do univariate or multivariate survival analysis and make forest plot for the results of multivariate Cox proportional hazard survival analysis. The steps for screening signature are as following: At step1, users should perform differential expression analysis of genes in one or multiple microarray datasets or RNA-seq count datasets or the other expression datasets and then mark these differentally expressed (DE) genes selected with "up" and "down" using negative or positive t-values. At step2, retrieve survival (or clinical data) using these DE genes and construct a new survival data(age, sex, stages/smoking, month, status, and DE genes in column and patients in row). Note that expression data ofthe DE genes are listed in the right side in the survival data. At step 3, perform musvtest.R (multiple univariate survival tests) or mvstest (multiple multivariate survival tests) with covariates age, sex and/smoking ect. Use p-value to select genes in big difference between low and high-survival probalities and use HR and up and down-regulation to classify genes selected into up and down groups in multiple cohorts. At step 4,use weight.R to calculate weight values of each gene in signature and use signatureExp.R to caculate expression values of signature in all patients and move the expression values to the last column in survival data. At step 5, perform MUKMplot.R or MMKMplot.R on signature in the survival data to plot Kaplan-Meier survival curves.

Author(s)

Yuan-De Tan [aut, cre] (<https://orcid.org/0000-0002-0364-2223>), Yuguang Ban [ctb]

Maintainer: Yuan-De Tan <[email protected]>

Examples

data(GSE50081)
res<-musvtest(sdata=GSE50081,stn=3500,gn=3506,time="month",status="status",
quant=c("no",-0.2,0.2))

Survival data from cohort GSE50081

Description

This dataset was derived from cohort GSE50081. It contains observation of 129 patients and 3577 probeids (without gene names),two signaturs "up" and "down" and 17 clinical variables suchas sex, age, smoking, stages, status(death, relapse, moth). 3577 probeids listgene expression values in 129 patients.

Usage

data("GSE50081")

Format

A data frame with 129 observations on the following 3596 variables.

sex1

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sex

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cell_type

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smoking

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month

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X227848_at

a numeric vector

X209613_s_at

a numeric vector

X213317_at

a numeric vector

X241672_at

a numeric vector

X229542_at

a numeric vector

X209612_s_at

a numeric vector

X223836_at

a numeric vector

X205982_x_at

a numeric vector

X211735_x_at

a numeric vector

X230469_at

a numeric vector

X206742_at

a numeric vector

X214387_x_at

a numeric vector

X209904_at

a numeric vector

X205952_at

a numeric vector

X217046_s_at

a numeric vector

X214135_at

a numeric vector

X209074_s_at

a numeric vector

X206651_s_at

a numeric vector

X209469_at

a numeric vector

X215454_x_at

a numeric vector

X205866_at

a numeric vector

X213456_at

a numeric vector

X230560_at

a numeric vector

X206209_s_at

a numeric vector

X210081_at

a numeric vector

X232578_at

a numeric vector

X209470_s_at

a numeric vector

up

a numeric vector

down

a numeric vector

Source

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50081

References

Der SD, Sykes J, Pintilie M, Zhu CQ et al. Validation of a histology-independent prognostic gene signature for early-stage, non-small-cell lung cancer including stage IA patients. J Thorac Oncol 2014 Jan;9(1):59-64. PMID: 24305008.

Examples

data(GSE50081)

Multivariate Kaplan-Meier survival curve plot

Description

Function MKMplot plots the outcome of multivariate survival analysis of patients in a cohort. Independent variable is specified as a gene or a signature. Covariates are sex, age, stage, genotype etc. If user needs one or multiple covariates, for example,smoking, tumor stage, etc., user can use X to specify the covariates.

Usage

MKMplot(data, mol, X, HR="hazard risk",time = "month", status = "status", 
sml="hv",quant=c("No",-0.2,0.2),plotmethod="plot",adjx)

Arguments

data

survival data including clinical data such as status, month, age, sex and/or smoking and expression data of genes or signatures.

mol

char value specified a gene symbol or a gene id or a signature existed in data or int value for a column number of a specified gene or a signature in data.

X

a string or string vector for one or multiple specified covariates. For example, X="smoking" or X=c("age","sex",smoking","genotype"). 10 covariates are limited in the current version. All covariates should be listed in the data.

HR

a string to specify hazard risk or hazard rate. If HR="Hazard risk" or "Hazard_risk", then plot would show coefficient, which has negative, zero, or positive value. The domain is (-\infty,\infty). The Negative value indicates reduction of hazard risk while the positive value suggests increment of risk. Zero suggests no change of hazard risk. If HR = "hazard rate" or "hazard_rate", then plot would show exp(coefficient), which the value is from 0 to \infty and HR < 1 indicates that hazard risk is reduced and HR > 1 means that hazard risk is increased. The default is "hazard risk". HR is only used in plot.

time

string for survival time and may be one of c("day", "month", "year"), depending on the clinical data. The default value is "month".

status

string to specify status name in the input survival data. For example, status may be "death", "relapse", or "status", depending on user's data. The default value is "status".

sml

surv.median.line: character vector for drawing a horizontal/vertical line at median survival. Allowed values include one of c("none", "hv", "h", "v"). v: vertical, h:horizontal. The value of sml is used in only ggsurvplot. The default is "hv".

quant

vector for quantile, low and high values. the low and high values are used to define or classify low and high expression groups. If quantile is "yes" or "YES", then the low and high are non-negative precent values, for example, quant=c("yes",0.25,0.75). If quantile is "no", then the low and high values are z-scores, the low value may be negative. For example, quant=c("no",-0.2, 0.2). The quantile = "yes" or = "No" may produce different results of survival analysis. User should carefully choose qunatile or no quantile according to the data. The default values are c("no",-0.2,0.2).

plotmethod

string value: choose a method to plot Kaplan-Meier survival curves. In current version, we have two methods for chose: plot and ggsurvplot. The defauld is plot method. In plot method, we show p-value for result of Ward t-test but in ggsurvplot, we show p-value for the result of log-rank test.

adjx

numeric value used to adjust x-axis position of p-value and HR in only plot.

Details

survival data contain clinical data such as status, month, age, sex and/or smoking and expression of gene or protein. The status may be death, recurrence or relapse and must be a binary variable: 1 for an event (such as death) or 0 for no event (such as alive). The month, age, and gene are numeric continuous variables but sex is a binary variable. The other covariates may be numeric continuous or binary variables. They are listed in column and patients or observations are listed in row.

Value

output a survival curve plot of multivariate survival analysis.

Note

To plot outcome of univariate survival, user can use UKMplot. All inputting parametes are not sensitive to upper or lower. That is, user can input upper or lower string or letter. For example, both time ="MONTH" or time = "month" work.

Author(s)

Yuan-De Tan
[email protected]
[email protected]
Yuguang Ban
[email protected]

See Also

UKMplot,MUKMplot,MMKMplot

Examples

require(survival)
require(ggplot2)
data(GSE50081)
MKMplot(data=GSE50081,mol=56,X=c("t.stage","n.stage",	"m.stage"),time="month",
status="status1",sml="none",quant=c("No",-0.2,0.2),plotmethod="ggsurvplot",
adjx = 5)

Multiple multivariate Kaplan-Meier survival curve plots

Description

Function MMKMplot plots outcomes of multivariate survival analyses of patients with covariates age and sex in a cohort with a specified set of genes. Each gene has a plot and each plot takes a page.

Usage

MMKMplot(sdata, stn, gn, X, HR="hazard risk", status = "status", 
time = "month", sml="hv",quant=c("No",-0.2,0.2),plotmethod="plot",adjx,
outdir, file)

Arguments

sdata

survival data including clinical data such as status, month, age, sex, and expressions of genes or expressions of proteins. Status such as death, recurrence or relapse must be 1 for event (such as death) or 0 for no event (such as alive), month is numeric data, age is numeric data, sex is binary data and genes are numeric data. They are listed in columns and patients are listed in rows.

stn

character value specifying gene symbol or gene id existed in sdata or int value specifying column number for the first gene in survival data.

gn

character value specifying gene symbol or gene id existed in sdata or int value specifying column number for the last gene in survival data.

X

string vector for covariate(s), an option with inputting names of one, two, three or more covariates. For example, X="smoking", X=c("age","sex","smoking","stage_n" ). The number of covariates is limited to 10. All covariates should be listed in the data.

HR

a string for specifying hazard risk or hazard rate. If HR="Hazard risk" or "Hazard_risk", then plot would show coefficient, which has negative, zero, or positive value. The domain is (-\infty,\infty). The Negative value indicates reduction of hazard risk while the positive value suggests increment of risk. Zero suggests no change of hazard risk. If HR = "hazard rate" or "hazard_rate", then plot would show exp(coefficient), which the value is from 0 to \infty and HR < 1 indicates that hazard risk is reduced and HR > 1 means that hazard risk is increased. The default is "hazard risk". HR is only used in plot.

status

string for a specifying status name. For example, status may be death, relapse or recurrence. User can set status="death", "relapse" or "recurrence" or "status", depending on the data.

time

string for survival time and may be one of c("day", "month", "year"), depending on the clinical data. The default value is "month".

sml

surv.median.line: character vector for drawing a horizontal/vertical line at median survival. Allowed values include one of c("none", "hv", "h", "v"). v: vertical, h:horizontal.The value of sml is used in only ggsurvplot. The default is "hv".

quant

vector for quantile, low and high values. the low and high values are used to define or classify low and high expression groups. If quantile is "yes" or "YES", then the low and high are non-negative precent values, for example, quant=c("yes",0.25,0.75). If quantile is "no", then the low and high values are z-scores, the low value may be negative. For example, quant=c("no",-0.2, 0.2). The quantile = "yes" or = "No" may produce different results of survival analysis. User should carefully choose quantile or no quantile according to the data. The default values are c("no",-0.2,0.2).

plotmethod

string value: choose a method to plot Kaplan-Meier survival curves. In current version, we have two methods for choice: plot and ggsurvplot. The defauld is plot method. In plot method, we show p-value for result of Ward t-test but in ggsurvplot, we show p-value for the result of log-rank-sum test.

adjx

numeric value used to adjust x-axis position of p-value and HR in only plot.

outdir

string, a path to save a file. If user uses setwd to set a dir for saving file, the outdir can be set "NULL", MMKMplot can automatically save pdf file in this dir folder in user local computer.

file

string for file name. If user sets a path with setwd or a path to outdir, then file just sets file name. The file is a pdf file containing all plot pages.

Value

output multiple pdf pages for multiple survival curve plots and saved in a outputting pdf file. If file ="NULL", MUKMplot would output the last survival plot page.

Note

User may not perform this function if unnecessary.

All inputting parameters are not sensitive to upper or lower. That is, user can input upper or lower string or letter. For example, both time ="MONTH" or time = "month" work.

Author(s)

Yuan-De Tan
[email protected]
[email protected]
Yuguang Ban
[email protected]

See Also

UKMplot,MKMplot,MUKMplot

Examples

data(GSE50081)
XX=c("age","sex","t.stage","n.stage","m.stage")
hr="hazard rate"

MMKMplot(sdata=GSE50081,stn="X232578_at", gn="down",X=XX,HR=hr,status="status1", 
time="month", quant=c("yes",0.25,0.75),plotmethod="plot",adjx = 3.5,file =
"NULL")

Function multiple univariate Kaplan-Meier survival curve plots

Description

MUKMplot plots the outcomes of univariate survival analyses of patients in a cohort using all selected genes.

Usage

MUKMplot(svdata, stn, gn,HR="hazard risk",time = "month", status = "status", 
         sml="hv",quant=c("No",-0.2,0.2),plotmethod="plot",adjx, outdir = 
         "NULL", file)

Arguments

svdata

survival data including clinical data such as status, month, and expressions of genes or proteins. Status such as death, recurrence or relapse must be 1 for event (such as death) or 0 for no event (such as alive). Genes or signatures are numeric continuous variables. They are listed in columns and patients or observations are listed in rows.

stn

character value specifying gene symbol or gene id existed in sdata or int value specifying column number for the first gene in survival data.

gn

character value specifying gene symbol or gene id existed in sdata or int value specifying column number for the first gene in survival data.

HR

a string for specifying hazard risk or hazard rate. If HR="Hazard risk" or "Hazard_risk", then plot would show coefficient, which has negative, zero, or positive value. The domain is (-\infty,\infty). The Negative value indicates reduction of hazard risk while the positive value suggests increment of risk. Zero suggests no change of hazard risk. If HR = "hazard rate" or "hazard_rate", then plot would show exp(coefficient), which the value is from 0 to \infty and HR < 1 indicates that hazard risk is reduced and HR > 1 means that hazard risk is increased. The default is "hazard risk".

time

string for survival time and may be one of c("day", "month", "year"), depending on the clinical data. The default value is "month".

status

string for a specifying status name. For example, status may be death, relapse or recurrence. User can set status="death", "relapse" or "recurrence" or "status", depending on the data.

sml

surv.median.line: character vector for drawing a horizontal/vertical line at median survival. Allowed values include one of c("none", "hv", "h", "v"). v: vertical, h:horizontal.The value of sml is used in only ggsurvplot. The default is "hv".

quant

vector for quantile, low and high values. the low and high values are used to define or classify low and high expression groups. If quantile is "yes" or "YES", then the low and high are non-negative precent values, for example, quant=c("yes",0.25,0.75). If quantile is "no", then the low and high values are z-scores, the low value may be negative. For example, quant=c("no",-0.2, 0.2). The quantile = "yes" or = "No" may produce different results of survival analysis. User should carefully choose quantile or no quantile according to the data. The default values are c("no",-0.2,0.2).

plotmethod

string value: choose a method to plot Kaplan-Meier survival curves. In current version, we have two methods for choice: "plot" and "ggsurvplot". The defauld is plot method. In plot method, we show p-value for result of Ward-test but in ggsurvplot, we show p-value for the result of log-rank test.

adjx

numeric value used to adjust x-axis position of p-value and HR in only plot.

outdir

string for a folder path to save the image file. If user uses setwd to set a path to save the image file, then outdir is not necessary to be given. The default outdir is "NULL".

file

string for a file name or path and file name. If user sets a path with setwd or set path to outdir, then file just contain file name. The file is pdf file containing all plot pages.

Value

output multiple pdf pages for multiple survival curve plots and saved in a outputting pdf file. If file ="NULL", MUKMplot would output the last survival plot page.

Note

User can use MKMplot to plot all signatures and gives a plot file name to save all signature suvival curve plots.

All inputting parameters are not sensitive to upper or lower. That is, user can input upper or lower string or letter. For example, both time ="MONTH" or time = "month" work.

Author(s)

Yuan-De Tan
[email protected]
[email protected]
Yuguang Ban
[email protected]

See Also

UKMplot,MMKMplot,MKMplot

Examples

data(TCGA_survivalData)
MUKMplot(svdata =TCGA_survivalData,stn=157,gn=160,time ="month", status="status",
plotmethod="plot",adjx = 170,file="NULL")

Multiple univariate suvival tests with a set of genes

Description

Function musvtest performs SKMCresult by an iteration from the specified first gene to the specified last gene. The output of musvtest is used to build a weight vector for signature survival analysis.

Usage

musvtest(sdata,stn,gn,time="month",status="status",quant=c("No",-0.2,0.2))

Arguments

sdata

survival and gene-expression data containing patients in row, survival status for death or recurrence or relapse, survival time such as month, day or year and a set of genes in columns.

stn

character value specifying the first gene symbol or gene id existed in sdata or int value specifying column number for the first gene in survival data.

gn

character value specifying the last gene symbol or gene id existed in sdata or int value specifying column number for the last gene in survival data.

time

string for survival time and may be one of c("day", "month", "year"), depending on the clinical data. The default value is "month".

status

string for survival status which is binary variable: 1 for event occurrence and 0 for no event occurrence. status may be "death","relapse" or "recurrence", depending on clinical data.

quant

vector for quantile, low and high values. the low and high values are used to define or classify low and high expression groups. If quantile is "yes" or "YES", then the low and high are non-negative precent values, for example, quant=c("yes",0.25,0.75). If quantile is "no", then the low and high values are z-scores, the low value may be negative. For example, quant=c("no",-0.2, 0.2). The quantile = "yes" or = "No" may produce different results of survival analysis. User should carefully choose quantile or no quantile according to the data. The default values are c("no",-0.2,0.2).

Details

Patient survival status is a binary variable with 1 for an event (such as death) and 0 for no event(such as alive). Genes have expression values(numeric values), which are used to calculate z-scores for classifying patients into two groups: high-expression patients and low-expression patients. SKMCresult performs univariate Cox proportional hazard survival analyses of patients with expression values of a specified gene and outputs hazard risk (HR), z-score and p-value of this specified gene. At first, user can run this function by performing musvtest to screen genes for prognostic signature by using HRs, z-scores, and p-values. Once getting a set of genes for signature, user can perform this function to build a weight vector using

wi=log10(pi)i=1glog10(pi)w_i=\frac{log_{10}(p_i)}{\sum_{i=1}^g{log_{10}(p_i)}}

where pip_i is p-value for Ward-test of gene i. For a patient, the signature score or expression value is given by weighting expression values of genes in the signature:

yj=igwixijy_j=\sum_{i}^g{w_ix_{ij}}

where xijx_{ij} is expression of gene i in patient j.

Value

output a matrix with n rows for gene name and hazard risk, hazard rate, standard error, z-value and p-value of each gene.

Note

All inputting parameters are not sensitive to upper or lower. That is, user can input upper or lower string or letter. For example, both time ="MONTH" or time = "month" work.

Author(s)

Yuan-De Tan
[email protected]
[email protected] Yuguang Ban
[email protected]

See Also

SKMCresult

Examples

data(GSE50081)
res<-musvtest(sdata=GSE50081,stn=3500,gn=3506,time="month",status="status")
#res
#              Gene Hazad risk hazard rate standard error    z-value     p-value
#3500  X209170_s_at -0.6510414   0.5215024      0.3133664 -2.0775721 0.037748792
#3501   X1556325_at -0.6041918   0.5465159      0.3507459 -1.7225913 0.084962455
#3502    X228915_at -0.4992865   0.6069636      0.3394520 -1.4708606 0.141328818
#3503 X1555216_a_at -0.5465844   0.5789238      0.3143044 -1.7390290 0.082029656
#3504  X203548_s_at -0.2004345   0.8183751      0.3018504 -0.6640193 0.506677970
#3505    X205433_at -1.3528063   0.2585138      0.4134465 -3.2720229 0.001067809
#3506    X209614_at -0.8389441   0.4321666      0.3905470 -2.1481262 0.031703733

Multivariate survival analysis with multiple specified independent variables

Description

Function MVKMresult performs multivariate Cox proportional hazard survival analysis with a set of patients and an independent variable (a specified gene or a feature) and a set of covariates (age, sex and/or smoking or stage) and outputs hazard risks (HR), z-scores, and p-values of the gene and these covariates.

Usage

MVKMresult(data,X,mol, status="status",time="month",quant=c("No",-0.2,0.2))

Arguments

data

survival data containing p patients in row, s survival variables such as survival status for death, recurrence or relapse, survival time such as day, month,or year, covariates age, sex and/or smoking, etc. and a set of genes in column.

X

string for covariate(s), number of covariates is limited to 10. If X=NULL, then MVKMresult would be stopped.

mol

int value for column number of the first gene specified.

status

string for survival status of patients, may be "relapse" or "recurrence" or "death". User can set status="death", "relapse" or "recurrence","status" depending on user's survival data. The default value is "status".

time

string for survival time and may be one of c("day", "month", "year"), depending on the clinical data. The default value is "month".

quant

vector for quantile, low and high values. the low and high values are used to define or classify low and high expression groups. If quantile is "yes" or "YES", then the low and high are non-negative precent values, for example, quant=c("yes",0.25,0.75). If quantile is "no", then the low and high values are z-scores, the low value may be negative. For example, quant=c("no",-0.2, 0.2). The quantile = "yes" or = "No" may produce different results of survival analysis. User should carefully choose quantile or no quantile according to the data. The default values are c("no",-0.2,0.2).

Details

Function MVKMresult performs multivariate Cox proportional hazard survival analyses with p patients and a specified gene and a set of covariates specified and outputs hazard risk (HR),z-score and p-value for the specified gene or signature and covariates.

Value

output a matrix with one row and multiple columns for gene name, Hazard risk, hazard rate, standard error, z-value, p-value of gene and covariates.

Note

User can also use SKMCresult to screen a prognostic signature and a weight vector without covariates.

All inputting parameters are not sensitive to upper or lower. That is, user can input upper or lower string or letter. For example, both time ="MONTH" or time = "month" work.

Author(s)

Yuan-De Tan
[email protected]
[email protected]
Yuguang Ban
[email protected]

See Also

SKMCresult,musvtest,mvstest

Examples

data(GSE50081)
res<-MVKMresult(data=GSE50081,X=c("t.stage","n.stage","m.stage"),mol=3500,
status="status",time="month",quant=c("no",-0.2,0.2))

Multivariate Cox proportional hazard survival analyses with multiple genes

Description

Function mvstest performs MVKMresult by iteration from the first gene to the last gene. The output result of musvtest is used to build a vector of weights for screening genes as prognostic signature or doing signature survival analysis.

Usage

mvstest(sdata,X,stn,gn, status,time,quant=c("No",-0.2,0.2))

Arguments

sdata

survival data containing p patients in row, survival status for death or recurrence or relapse, survival time such as day, month, or year, and covariates age, sex and/or smoking, tumor stage, or chemotherapy, and a set of genes in column.

X

string specifying one or multiple covariates such as age, sex, smoking, or tumor stage or genotype. The number of covariates in X is limited to 10.

stn

character value specifying gene symbol or gene id existed in sdata or int value specifying column number for the first gene in survival data.

gn

character value specifying gene symbol or gene id existed in sdata or int value specifying column number for the last gene in survival data.

status

string for survival status which must be binary variable: 1 for event occurrence and 0 for no event occurrence. status may be "death", "relapse" or "recurrence", depending on clinical data.

time

string for survival time and may be one of c("day", "month", "year"), depending on the clinical data. The default value is "month".

quant

vector for quantile, low and high values. the low and high values are used to define or classify low and high expression groups. If quantile is "yes" or "YES", then the low and high are non-negative precent values, for example, quant=c("yes",0.25,0.75). If quantile is "no", then the low and high values are z-scores, the low value may be negative. For example, quant=c("no",-0.2, 0.2). The quantile = "yes" or = "No" may produce different results of survival analysis. User should carefully choose quantile or no quantile according to the data. The default values are c("no",-0.2,0.2).

Details

Patient survival status is binary variable with 1 for event (such as death) and 0 for no event (such as alive). Genes have expression values(numeric values), which are used to calculate z-scores for classifying patients into two groups: high-expression patients and low-expression patients. SKMCresult performs univariate Cox proportional hazard survival analyses of patients with expression values of a specified gene and outputs hazard risk (HR), z-score and p-value of this specified gene. At first, user can run this function by performing msvtest to screen genes for prognostic signature by using HRs, z-scores, and p-values. Once getting a set of genes for signature, user can perform this function to build a weight vector using

wi=log10(pi)i=1glog10(pi)w_i=\frac{log_{10}(p_i)}{\sum_{i=1}^g{log_{10}(p_i)}}

where pip_i is p-value for Ward-test of gene i. For a patient, the signature score or expression value is given by weighting expression values of g genes in the signature:

yj=igwixijy_j=\sum_{i}^g{w_ix_{ij}}

where xijx_{ij} is expression of gene i in patient j.

Value

output a matrix with n rows for n genes, m+1 columns for Hazard risk, hazard rate, standard error, z-value, p-value of gene and m covariates.

Note

All inputting parameters are not sensitive to upper or lower. That is, user can input upper or lower string or letter. For example, both time ="MONTH" or time = "month" work.

Author(s)

Yuan-De Tan
[email protected]
[email protected]
Yuguang Ban
[email protected]

See Also

MVKMresult

Examples

data(GSE50081)

res<-mvstest(sdata=GSE50081,X=c("t.stage","n.stage"),stn=3550,gn=3555,
status="status",time="month",quant=c("No",-0.2,0.2))

results of univariate Cox proportional hazard analysis of patients with ADC in three cohorts.

Description

The "results" is a list consisting of three results generated by performing univariate Cox proportional hazard survival analysis in three different cohorts. Each result has four columns gene(gene symbol or geneid), zahard.ratio, zscore, and p.value for each gene. The results list is used to construct weight vector in the signature.

Usage

data("results")

Format

The format is: List of 3 $ :'data.frame': 28 obs. of 4 variables: ..$ Gene : chr [1:28] "CDKN1C" "CDKN2B" "DAB2IP" "DCC" ... ..$ Hazard.ratio: num [1:28] 1.027 0.685 0.663 0.494 0.634 ... ..$ zscore : num [1:28] 0.0734 -1.162 -1.4084 -1.9798 -1.4282 ... ..$ p.value : num [1:28] 0.9415 0.2452 0.159 0.0477 0.1532 ... $ :'data.frame': 26 obs. of 4 variables: ..$ Gene : chr [1:26] "201335_s_at" "201621_at" "203185_at" "203525_s_at" ... ..$ Hazard.ratio: num [1:26] 2.712 0.849 0.742 0.99 0.402 ... ..$ zscore : num [1:26] 1.7257 -0.3047 -0.6031 -0.0198 -1.6817 ... ..$ p.value : num [1:26] 0.0844 0.7606 0.5464 0.9842 0.0926 ... $ :'data.frame': 34 obs. of 4 variables: ..$ Gene : chr [1:34] "age" "gender" "sex" "cell_type" ... ..$ Hazard.ratio: num [1:34] NA NA NA NA NA ... ..$ zscore : num [1:34] NA NA NA NA NA ... ..$ p.value : num [1:34] NA NA NA NA NA ...

Examples

data(results)

Weights of genes in a signature

Description

Weights of genes in a signature were estimated by using the following equation

wi=log10(pi)i=1glog10(pi)w_i=\frac{log_{10}(p_i)}{\sum_{i=1}^g{log_{10}(p_i)}}

where pip_i is p-value for Ward-test of gene i in survival analysis.

Usage

data("signature_weight")

Format

A data frame with 84 observations on the following 2 variables.

stage3_down

a character vector

weight.7

a numeric vector

Details

signature_weight is a matrix with g×\times 2 or 3 where g is number of genes in a signature and there are two or three columns for gene id or gene name and weights.

Examples

data(signature_weight)

Signature expression or signature score

Description

Function signatureExp.R is used to give signature expression or score across all patients in a cohort data by using weight vector of a signature.

Usage

signatureExp(svdata,weight)

Arguments

svdata

a survival dataset containing clinic data such as death or relapse status, month, covariates age, sex and/smoking, stages, therapy etc. and a set of genes containing subset of genes in the signature in column.

weight

a matrix that contains gene and/or gene_id and weight columns.

Details

a matrix with g×(2or3)g \times (2 or 3). If weight contains two columns, then first column must be gene or gene_id and the second column must be weight. If weight has three columns, then the first two columns are gene and gene_id but the third column must be weight. Gene name or gene_id in weigth must be matched with gene name or gene_id in the survival data.

Value

a survival dataset with signature scores of patients.

Author(s)

Yuan-De Tan
[email protected]
[email protected]

See Also

weight

Examples

data(TCGA_survivalData)
data(signature_weight)
res1<-signatureExp(svdata=TCGA_survivalData,weight=signature_weight)

Univariate Cox proportional hazard survival analysis with a specified independent variable

Description

Function SKMCresult performs univariate Cox proportional hazard survival analysis of patients with a specified independent variable or a gene without covariates and outputs hazard risk (HR), z-score, and p-value of this specified gene.

Usage

SKMCresult(data,mol, time="month", status="status",quant=c("No",-0.2,0.2))

Arguments

data

survival and gene-expression data containing patients in row, survival status for death, recurrence or relapse, survival time and a set of genes in column.

mol

char value specified a gene symbol or a gene id or a signature existed in data or int value for a column number of a specified gene or a signature in data.

time

string for survival time and may be one of c("day", "month", "year"), depending on the clinical data. The default value is "month".

status

string for survival status of patients, may be "relapse" or "recurrence" or "death". User can set status="death", "relapse" or "recurrence","status" depending on user's survival data. The default value is "status".

quant

vector for quantile, low and high values. the low and high values are used to define or classify low and high expression groups. If quantile is "yes" or "YES", then the low and high are non-negative precent values, for example, quant=c("yes",0.25,0.75). If quantile is "no", then the low and high values are z-scores, the low value may be negative. For example, quant=c("no",-0.2, 0.2). The quantile = "yes" or = "No" may produce different results of survival analysis. User should carefully choose quantile or no quantile according to the data. The default values are c("no",-0.2,0.2).

Details

Patient survival status is binary variable with 1 for event (such as death) and 0 for no event(such as alive). Genes have expression values(numeric values), which are used to calculate z-scores for classifying patients into two groups: high-expression patients and low-expression patients. SKMCresult performs univariate Cox proportional hazard survival analyses of patients with expression values of a specified gene and outputs hazard risk (HR), z-score and p-value of this specified gene.

Value

output a matrix with one row and 6 columns for gene name, Hazard risk, hazard rate, standard error, z-value, p-value of the specified gene.

Note

All inputting parameters are not sensitive to upper or lower. That is, user can input upper or lower string or letter. For example, both time ="MONTH" or time = "month" work.

Author(s)

Yuan-De Tan
[email protected]
[email protected]
Yuguang Ban
[email protected]

See Also

MVKMresult,musvtest,mvstest

Examples

data(GSE50081)
res<-SKMCresult(data=GSE50081,mol=350, time="month", status="status")

Forestplot for result of multivariate Cox proportional hazard survival analysis

Description

This function provides a publishable forestplot figure that shows results of multivariate Cox proportional hazard regression analysis of patients in a cohort.

Usage

survivalForest(sdata,xtick)

Arguments

sdata

results of multivariate survival analyses,outputted by performing MKMplot.

xtick

x-coordinate size in forestplot. For example, user can set xtick=c(-2,-1,0,1,2)

Details

The data includes column "model" and/or stage", "variable","HR","SE", and "p_value". In inputing data, stage may be stage IA, stageIB, stageII, stageIIA, stageIIB, stageIII, etc. The Variable may contain signature, sex, age, smoking, genotype,etc.. The variable column may be named with "Variate","variate", "Variable","variable", "factor" or "category" word. "HR" is hazard risk, also called coefficient or beta of Cox proportional hazard regression. So, HR column may be named with "HR","hazard risk", "coefficient","beta" or "Beta" word. "SE" is standard error and may be named with "se","SE" or "standard error". "p_value" is p-value for Ward test/ranksum test, may be named with "pvalue","p_value", "p-value","p value","PV" or "pv" word. The rows include signature (gene or biomarker), age, sex and covariate(s).

Value

output a plot figure.

Note

sdata may contain multiple models such as model1, model2, model3. Model1: signature, age,sex. Model2: signature, age, sex, smoking. Model 3: signature, age, sex, smoking, and genotype. User can use empty row to separate these models.

Author(s)

Yuan-De Tan
[email protected]
[email protected]
Yuguang Ban
[email protected]

See Also

forestplot

Examples

#library(forestplot)
data(TCGA_forestplt)
xtick=c(-1,-0.5,0,0.5,1)
#pdf(file="TCGA_survival_forestplot.pdf")
survivalForest(sdata=TCGA_forestplt,xtick=xtick)
#dev.off()

Data for forestplot

Description

The data are derived from results of performing multivariate Cox proportional hazard survival analysis on patients with ADC in TCGA lung cancer.

Usage

data("TCGA_forestplt")

Format

A data frame with 28 observations on the following 5 variables.

stage

a character vector

variate

a character vector

beta

a numeric vector

se

a numeric vector

p_value

a numeric vector

Details

The dataset was constructed with 28 observations for up and down signatures, sex and age in stages 1A, 1B, stage2 and stage3 and 5 variables stage, variate, beta, se and p_value.

Examples

data(TCGA_forestplt)

TCGA data for survival analysis

Description

TCGA data is a clinical and microarray dataset consisting of 572 samples (observations) in row and 162 variables (20 clinical variables such as age, sex month, status,race, genotype and 142 DE genes)

Usage

data("TCGA_survivalData")

Format

A data frame with 572 observations on the following 162 variables.

sample

a character vector

sampleID

a numeric vector

status

a numeric vector

vital_status.demographic

a character vector

day

a numeric vector

month

a numeric vector

age

a numeric vector

geneder

a character vector

sex

a numeric vector

race.demographic

a character vector

race

a numeric vector

year_of_birth.demographic

a numeric vector

year_of_death.demographic

a numeric vector

age_at_diagnosis.diagnoses

a numeric vector

days_to_death.demographic

a numeric vector

egfr_mutation_performed

a character vector

eml4_alk_translocation_performed

a character vector

followup_treatment_success

a character vector

additional_pharmaceutical_therapy

a character vector

additional_radiation_therapy

a character vector

SLC25A13

a numeric vector

PSMC4

a numeric vector

MRE11A

a numeric vector

PTCD2

a numeric vector

STYK1

a numeric vector

GOLGA5

a numeric vector

IARS2

a numeric vector

KIF2A

a numeric vector

HLTF

a numeric vector

C14orf166

a numeric vector

GEMIN2

a numeric vector

CDC6

a numeric vector

MSH2

a numeric vector

FKBP3

a numeric vector

PSMC6

a numeric vector

PSMB5

a numeric vector

CSNK2A1

a numeric vector

KNOP1

a numeric vector

AVL9

a numeric vector

DNAJC2

a numeric vector

RPA3

a numeric vector

TMEM106B

a numeric vector

COA1

a numeric vector

GAPDH

a numeric vector

FAF2

a numeric vector

UCHL5

a numeric vector

CBX3

a numeric vector

HNRNPA2B1

a numeric vector

CALU

a numeric vector

GAD1

a numeric vector

PDLIM4

a numeric vector

TIMM17A

a numeric vector

NAA35

a numeric vector

GOLM1

a numeric vector

SULF1

a numeric vector

FANCI

a numeric vector

CLTC

a numeric vector

SDHC

a numeric vector

MRPL9

a numeric vector

ACP1

a numeric vector

FBXO28

a numeric vector

PDIA6

a numeric vector

SIGMAR1

a numeric vector

ADAM12

a numeric vector

XRCC4

a numeric vector

PLOD2

a numeric vector

TMEM87B

a numeric vector

BUB3

a numeric vector

DPY19L4

a numeric vector

HLCS

a numeric vector

PSMC2

a numeric vector

SLBP

a numeric vector

ORC5

a numeric vector

SGPL1

a numeric vector

GREM1

a numeric vector

VKORC1

a numeric vector

ZNF146

a numeric vector

CHAF1A

a numeric vector

TK1

a numeric vector

FEN1

a numeric vector

FRMD5

a numeric vector

DPY19L1

a numeric vector

CKAP5

a numeric vector

ZNF93

a numeric vector

SEMA4B

a numeric vector

PRMT3

a numeric vector

ERO1L

a numeric vector

DNAJC9

a numeric vector

FMO3

a numeric vector

FHL1

a numeric vector

DAPK2

a numeric vector

PREX2

a numeric vector

VPS13D

a numeric vector

TGFBR3

a numeric vector

NDST1

a numeric vector

LIMS2

a numeric vector

GLI2

a numeric vector

ACACB

a numeric vector

PIK3C3

a numeric vector

PCM1

a numeric vector

RUNX1T1

a numeric vector

NCOA1

a numeric vector

TTC28

a numeric vector

CBX7

a numeric vector

CPED1

a numeric vector

PTGDS

a numeric vector

SPOCK2

a numeric vector

GAB1

a numeric vector

FOXP1

a numeric vector

RAP1A

a numeric vector

TCF21

a numeric vector

WDR35

a numeric vector

WBP4

a numeric vector

SORBS3

a numeric vector

TBX2

a numeric vector

ITIH5

a numeric vector

PZP

a numeric vector

ATP1B2

a numeric vector

CBFA2T3

a numeric vector

GSTM5

a numeric vector

GSTM3

a numeric vector

ADAMTS8

a numeric vector

GYPC

a numeric vector

ARHGAP24

a numeric vector

PDE5A

a numeric vector

FBLN5

a numeric vector

IQSEC1

a numeric vector

SNCA

a numeric vector

HMBOX1

a numeric vector

NFIB

a numeric vector

PAMR1

a numeric vector

SAP18

a numeric vector

IGSF10

a numeric vector

ANGPT1

a numeric vector

JAM2

a numeric vector

PTH1R

a numeric vector

NFASC

a numeric vector

DLC1

a numeric vector

FIGF

a numeric vector

PKNOX2

a numeric vector

NDRG2

a numeric vector

FRAT1

a numeric vector

ANAPC16

a numeric vector

TNXB

a numeric vector

SFTPC

a numeric vector

KCNK3

a numeric vector

SYNPO

a numeric vector

ID4

a numeric vector

PER1

a numeric vector

SLIT3

a numeric vector

FOXO4

a numeric vector

GJA4

a numeric vector

PCBP2

a numeric vector

ADARB1

a numeric vector

PARVA

a numeric vector

CFD

a numeric vector

ARHGEF15

a numeric vector

GPR20

a numeric vector

HSBP1

a numeric vector

RPS28

a numeric vector

TNXA

a numeric vector

FXYD1

a numeric vector

Source

https://www.cancer.gov/ccg/access-data

Examples

data(TCGA_survivalData)

A signature constructed with a set of tumor suppressor genes

Description

TS_signature was constructed with a set of 26 tumor suppressor genes screened from microarray data GSE19804 and cohorts GSE18842, GSE40419, and GSE21933 using differential analysis and bioinformatics methods.

Usage

data("TS_signature")

Format

A data frame with 28 observations on the following 2 variables.

probeid

a character vector

gene

a character vector

Details

TS signature has 26 tumor suppressor genes (26 probeids). These genes are normally expressed but repressed in cancer or tumor cells. Therefore, a TS signature also has low expression in normal tissues but high expression in cancer cells of patients.

References

Zhang, C., Jiang, M., Zhou, N. et al. Use tumor suppressor genes as biomarkers for diagnosis of non-small cell lung cancer. Sci Rep 11, 3596 (2021). https://doi.org/10.1038/s41598-020-80735-x.

Examples

data(ST_signature)

Univariate Kaplan-Meier survival curve plot

Description

Function UKMplot is used to plot outcome of survival analysis of patients in a cohort using a specified gene or a signature.

Usage

UKMplot(data,mol,HR="hazard risk", time="month",status="status", sml="hv",
      quant=c("No",-0.2,0.2), plotmethod="plot",adjx)

Arguments

data

survival data in which columns contain patient survival data such as survival status, survival month, age, sex,cell type and genes and rows list all patients. Status and sex are binary data. In status, 1 is defined as an event occurrece (such as death) and 0 as no event occurrence (such as alive). Month, age, and genes, signature are numeric and continuous data.

mol

char value specified a gene symbol or a gene id or a signature existed in data or int value for a column number of a specified gene or signature in data.

HR

a string for specifying hazard risk or hazard rate. If HR="Hazard risk" or "Hazard_risk", then plot would show coefficient, which has negative, zero, or positive value. The domain is (-\infty,\infty). The Negative value indicates reduction of hazard risk while the positive value suggests increment of risk. Zero suggests no change of hazard risk. If HR = "hazard rate" or "hazard_rate", then plot would show exp(coefficient), which the value is from 0 to \infty and HR < 1 indicates that hazard risk is reduced and HR > 1 means that hazard risk is increased. The default is "hazard risk". HR is only used in plot.

time

string for survival time and may be one of c("day", "month", "year"), depending on the clinical data. The default value is "month".

status

string for survival status of patients, may be "relapse" or "recurrence" or "death". User can set status="death", "relapse" or "recurrence","status" depending on user's survival data. The default value is "status".

sml

surv.median.line: character vector for drawing a horizontal/vertical line at median survival. Allowed values include one of c("none", "hv", "h", "v"). v: vertical, h:horizontal.The value of sml is used in ggsurvplot, not in plot. The default is "hv".

quant

vector for quantile, low and high values. the low and high values are used to define or classify low and high expression groups. If quantile is "yes" or "YES", then the low and high are non-negative precent values, for example, quant=c("yes",0.25,0.75). If quantile is "no", then the low and high values are z-scores, the low value may be negative. For example, quant=c("no",-0.2, 0.2). The quantile = "yes" or = "No" may produce different results of survival analysis. User should carefully choose quantile or no quantile according to the data. The default values are c("no",-0.2,0.2).

plotmethod

string value: choose a method to plot Kaplan-Meier survival curves. In current version, we have two methods for chose: plot and ggsurvplot. The defauld is plot method

adjx

a numeric value used to adjust x-axis position of p-value and HR in plot.

Details

UKMplot is a function invoked by MKMplot. By invoking UMKplot, MKMplot can make a set of survival plots for a set of genes or a set of signatures.

Value

outputs a survival curve plot of a specified gene.

Note

For a multivariate survival analysis, user can use MVKMplot to plot survival outcome.

All inputting parameters are not sensitive to upper or lower. That is, user can input upper or lower string or letter. For example, both time ="MONTH" or time = "month" work.

Author(s)

Yuan-De Tan
[email protected]
[email protected]
Yuguang Ban
[email protected]

See Also

MKMplot,MMKMplot,MUKMplot

Examples

require(survival)
require(ggplot2)
data(TCGA_survivalData)
UKMplot(data=TCGA_survivalData,mol=78,time="month", status="status",
quant=c("No",-0.2,0.2),adjx=100)
UKMplot(data=TCGA_survivalData,mol="RPS28",time="month", status="status",adjx=100)

Caculation of Weights for signature genes

Description

Weights for signature genes are calculated from the results obtained by performing Cox proportional hazard regression on the training survival datasets.

Usage

weight(results,signature)

Arguments

results

a list of multiple results obtained by performing survival analysis on the training datasets.

signature

a vector or matrix of genes screened by a method from survival data and expression data.

Details

The results file is a list of multiple results obtained by performing Cox proportional hazard survival analysis based on univariate models in multiple datasets. User can create this list by using results<-list(result1,result2,..., resultn). Signature may be a matrix with two columns and n rows. One column may be gene id(such as probe id or Ensembl id or NCBI Entrez id) and the other is gene symbol or gene name. Signature may be a vector(a set of genes or gene ids).

Value

Output a matrix where gene and/or gene id and weight in column and gene names and/or gene id values and weight values.

Note

Sum of weights may not be equal to 1 if some genes in results are lost.

Author(s)

Yuan-De Tan
[email protected]
[email protected]

Examples

data(TS_signature)
data(results)
res<-weight(results = results,signature = TS_signature)