drylm: Differential rhythmicity analysis for RNA-Seq datasets

In naef-lab/dryR: Differential RhythmicitY analysis

Differential rhythmicity analysis for RNA-Seq datasets

Description

This function performs a rhythmicity analysis based on linear models with a subsequent models selection. The function accepts a time series assuming normally distributed noise of two or more groups. The function outputs the parameters mean, phase and amplitude are for each group.

Usage

drylm(
  data,
  group,
  time,
  period = 24,
  sample_name = colnames(data),
  batch = rep("A", length(sample_name)),
  n.cores = 1
)

Arguments

data	matrix or vector containing data; if a matrix is provided each column represents a sample, each row represents a feature.
group	vector containing the name of each group (e.g. wildtype, knock-out).
time	vector containing numeric values of the zeiteber/circadian time for each sample.
period	numeric value to indicate period length of the oscillation. Default: period = 24 h.
sample_name	vector containing sample names. Default: colnames are sample names.
batch	vector containing potential batch effects between samples. Default: no batch effect.
nthreads	vector numeric value to indicate the threads for parallel computing .Default: 60 % of detected cores.

Details

DryR assesses rhythmicity and mean differences of gene expression in normal data. When necessary, a batch specific mean (m) can be given to the drylm function to account for technical batch effects. A technical batch effect is not allowed to be confounding so the resulting model matrix is fully ranked. To select an optimal gene-specific model, drylm first assesses rhythmicity across the different conditions. To this end, dryR defines different models across all groups. Models refined to have either zero (non-rhythmic pattern) or non-zero (rhythmic pattern) α and β coefficients for each analyzed group. Moreover, for some models the values of α and β can be also shared within any combination of all groups The coefficients α and β were used to calculate the phase (arctan(α/β)) and amplitude (log2-fold change peak-to-trough; 2sqrt(α^2+β^2) ) of a gene. Bayesian information criterion (BIC) based model selection was employed to account for model complexity using the following formula:

BIC_j = n ln(RSS_j/n)+ k ln(n)

with RSS the sum of residuals square of the multilinear regression, n the number of time points, and k the number of parameters. To assess the confidence of the selected model j we calculated the Schwarz weight (BICW):

BICW_j = e^(0.5ΔBIC_j)\ sum(e^0.5 ΔBIC_m), with ΔBIC_j - BIC_j - BIC_m*

m* is the minimum BIC value in the entire model set. drylm consideres the BICW_j as the confidence level for model j. The model with the highest BICW is selected as the optimal model within the set of all defined models. In a second iteration step, drylm set the coefficient α and β to the values of the selected model in the first regression. drylm then defined different models for the mean coefficient with differing or shared means between groups. Each model is solved using linear regression and each gene was assigned to a preferred model based on the BICW as described above for the first iteration.

Value

a list that contains the following data.frames: results (summary of results), parameters (rhythmic parameters), ncounts (normalized counts), counts (raw counts), cook (cook's distance)

Examples

data = log(simData[["countData"]]+1)
group = simData[["group"]]
time  = simData[["time"]]
dryList = drylm(data,group,time)
head(dryList[["results"]])    # data frame summarizing results
head(dryList[["parameters"]]) # coefficients: phase, amplitude and mean for each group
head(dryList[["ncounts"]])    # normalized counts

naef-lab/dryR documentation built on Feb. 25, 2024, 3:26 p.m.