Description Usage Arguments Details Value Author(s) References Examples
This is the main function of this package. It takes gene expression
matrix (X
), time points (tt
), a pre-defined list of gene sets
(genesets
), and several tuning parameters (see below) as input. It then
apply functional data analysis techniques and elastic-net regression
to define weights for genes that are shared by more than one gene sets
(the overlapping genes). Finally, it applies an extended Mann-Whitney
U test that incorporates both intergene correlation and weights
computed from the elastic-net regression to pre-defined gene sets
to obtain significance of non-constant temporal trend for each gene set.
1 2 3 |
X |
A gene expression matrix. Genes must be ordered as rows and
each column represent a time point. Row names must be gene names used
in |
tt |
A vector of ordered unique time points. |
genesets |
A list of pre-defined gene sets. Each element of this
list is a vector of gene names that are rownames of the |
lambda |
Roughness penalty (smoothing) parameter used by function
|
rr |
Number of repetitions at each unique time points. |
selection_k |
Method of choosing the number of principal
components. Choices are: |
FVE_threshold |
A positive number between 0 and 1. It is
used with the option |
nharm |
Number of eigenfunctions to be used to represent the overall temporal trend of each gene set. Default to 3. |
centerfns |
An indicator if to center functions in |
equiv.threshold |
This is a threshold to be used in function
|
lam1 |
The L1 (LASSO) penalty used in elastic-net regression. |
lam2 |
The L2 (ridge) penalty used in elastic-ent regression. |
alpha.level |
Significance level for gene set test (extended Mann-Whitney U test). Default to 0.05. |
sort |
An indicator if to sort the p-values from the smallest to
the largest. Default: |
Technical details of this procedure is documented in Yun Zhang, Juilee Thakar, Xing Qiu (2016).
A list with the following objects
pvals |
A vector of unadjusted p-values for pre-defined gene sets. |
weight.list |
A list of weights (a.k.a. empirical gene set membership) computed from the elastic-net regression. |
correlation |
Mean intergene correlation coefficient estimated from genes within each gene set. |
sig.genesets |
A vector of names (or indices) of significant gene sets
at |
Fstats |
A vector of F-statistics, which are gene-level summary statistics used in extended Mann-Whitney U test. |
Yun Zhang, Juilee Thakar, Xing Qiu
Yun Zhang, Juilee Thakar, Xing Qiu (2016) FUNNEL-GSEA: FUNctioNal ELastic-net Regression in Time-course Gene Set Enrichment Analysis, submitted to Bioinformatics.
1 2 3 4 5 | ## Load the sample data
data("H3N2-Subj1")
## It takes about 10 minutes to run on my Laptop; YMMV.
## Not run: t1 <- system.time(results1 <- FUNNEL.GSEA(X, tt, genesets=genesets))
|
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