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Package HarmonicRegression April 1, 2015 Type Package Title Harmonic Regression to One or more Time Series Version 1.0 Date 2015-04-01 Author Paal O. Westermark Maintainer Paal O. Westermark <pal-olof.westermark@charite.de> Fits the first harmonics in a Fourier expansion to one or more time series. Trend elimination can be performed. Computed values include estimates of amplitudes and phases, as well as confidence intervals and p-values for the null hypothesis of Gaussian noise. License MIT + file LICENSE VignetteBuilder knitr Suggests knitr Depends R (>= 2.10) NeedsCompilation no Repository CRAN Date/Publication 2015-04-01 19:27:09 R topics documented: harmonic.regression..................................... 2 rna.nasc........................................... 3 rna.polya.......................................... 4 Index 5 1

2 harmonic.regression harmonic.regression Harmonic Regression Estimates amplitudes and phases along with confidence intervals and p-values from a set of time series that may oscillate with a specified period. A model, per default y = m + acos(ωt) + bsin(ωt), is fitted to the time series. This model is equivalent to the model m + ccos(ωt φ), with amplitude c = (a 2 + b 2 ) and phase φ = atan2(b, a). P-values for c > 0 (more precisely: either a or b > 0 ) are computed by an F-test. Confidence intervals for the amplitudes and phases are computed by a linear error propagation approximation. Usage harmonic.regression(inputts, inputtime, Tau = 24, normalize = TRUE, norm.pol = FALSE, norm.pol.degree = 1, trend.eliminate = FALSE, trend.degree = 1) Arguments inputts inputtime Tau Matrix of time series. Rows correspond to time points, columns to samples. If a vector is provided, it is coerced to a matrix. Vector of the time points corresponding to the row in the time series matrix. Scalar giving the oscillation period to estimate and test for. normalize Boolean, set to TRUE if normalization is to be performed (default). Unless norm.pol=true, normalization is performed by dividing with the mean. norm.pol Boolean, set to TRUE if a polynomial should be fitted to each time series, and used for normalization. In this case, each point in a time series will be divided by the value of the fitted polynomial. Defaults to FALSE. norm.pol.degree Scalar indicating the polynomial degree for the normalization (ignored if norm.pol=false). trend.eliminate Boolean, set to TRUE if trend elimination is to be performed (see above). Defaults to FALSE. trend.degree Integer indicading the polynomial degree for the trend elimination, default is 1. Ignored when trend.eliminate=false, which is the default.

rna.nasc 3 Value The default setting is that the time series are normalized with their mean values. Optionally a polynomial of degree 1 or more is first fitted to each time series, whereupon the original time series are normalized by dividing with the fitted values at each point, thus trends in a fold-change sense are assumed. Another option is trend elimination, in which case the same model plus a polynomial: y = m + acos(ωt) + bsin(ωt) + et + ft 2 +... is fitted to the (possibly normalized) data. In this case, returned p-values still only concern the alternative c > 0 as defined above. Values returned include normalized time series (if normalization is performed), normalization weights (means or polynomial coefficients if polynomial normalilzation is used), fitted normalized curves, fitted non-normalized curves, a data frame of amplitudes and phases (in radians), p-values according to an F-test (Halberg 1967), Benjamini-Hochberg adjusted p-values, a data frame of approximately 1.96 standard deviations for the amplitude and phase estimates, a matrix of coefficients a and b and possibly c,..., the sum square resuduals after the fit for each time series, and the covariance matrix for the three independent variables (1, cos(ωt), and sin(ωt)). The latter can be used in post-processing e.g. to obtain individual p-values for coefficients by t-tests. A list containing: means Vector (if norm.pol=false) or matrix (otherwise) of the means or coefficients of the fitted polynomial used normts Matrix of mean-scaled or normalized-by-polynomial time series, same dimensionality as inputts fit.vals Matrix of model fitted values to inputts norm.fit.vals Matrix of model fitted values to the normalized (trend eliminated or mean scaled) time series pars Data frame of estimated amplitudes and phases (in radians, between 0 and 2π) pvals Vector of p-values according to an F-test of the model fit against a restricted model (mean-centering only) qvals Vector of Benjamini-Hochberg adjusted p-values ci Data frame of one-sided approximative 95% (2σ) confidence intervals for the estimated amplitudes and pha coeffs Matrix of estimated model parameters a and b ssr Vector of sum square residuals for the model fits df Scalar if inputts does not contain NAs and Vector otherwise, representing the degrees of freedom of the res ssx Matrix (3 times 3, if inputts does not contain NAs, a list of such matrices, one for each time series, otherwi References Halberg F, Tong YL, Johnson EA: Circadian System Phase An Aspect of Temporal Morphology; Procedures and Illustrative Examples. in: The Cellular Aspects of Biorhythms, Springer 1967. rna.nasc Menet et al. RNA-Seq Data Quantification of circadian transcriptional activity in mouse liver.

4 rna.polya Format Source a data frame with nascent RNA-seq data The nascent-seq data are thought to reflect transcriptional activities. Raw data was collected from the supplementary material of the original publication cited below. In that study, samples were collected at 6 different times of day in two biological replicates (fields ZT* in the data frame). The field mgi_symbol refers to MGI gene names. Jerome S Menet, Joseph Rodriguez, Katharine C Abruzzi, Michael Rosbash. Nascent-Seq reveals novel features of mouse circadian transcriptional regulation. elife 1:e00011 (2012). Examples data(rna.nasc) nasc.t <- seq(0, 44, 4) plot(nasc.t, rna.nasc["arntl", -1], type="b") rna.polya Menet et al. RNA-Seq Data Format Source Quantification of circadian transcriptional activity in mouse liver. a data frame with poly(a)+ RNA-seq data The poly(a)+-seq data represent mature mrna abundances. Raw data was collected from the supplementary material of the original publication cited below. In that study, samples were collected at 6 different times of day in two biological replicates (fields ZT* in the data frame). The field mgi_symbol refers to MGI gene names. Jerome S Menet, Joseph Rodriguez, Katharine C Abruzzi, Michael Rosbash. Nascent-Seq reveals novel features of mouse circadian transcriptional regulation. elife 1:e00011 (2012). Examples data(rna.polya) polya.t <- seq(0, 44, 4) plot(polya.t, rna.polya["arntl", -1], type="b")

Index harmonic.regression, 2 rna.nasc, 3 rna.polya, 4 5