Circadian rhythms are daily oscillations in physiology and behavior that can be assessed by recording body temperature, locomotor activity, or bioluminescent reporters, among other measures. These different types of data can vary greatly in waveform, noise characteristics, typical sampling rate, and length of recording. We developed 2 Shiny apps for exploration of these data, enabling visualization and analysis of circadian parameters such as period and phase. Methods include the discrete wavelet transform, sine fitting, the Lomb-Scargle periodogram, autocorrelation, and maximum entropy spectral analysis, giving a sense of how well each method works on each type of data. The apps also provide educational overviews and guidance for these methods, supporting the training of those new to this type of analysis. CIRCADA-E (Circadian App for Data Analysis–Experimental Time Series) allows users to explore a large curated experimental data set with mouse body temperature, locomotor activity, and PER2::LUC rhythms recorded from multiple tissues. CIRCADA-S (Circadian App for Data Analysis–Synthetic Time Series) generates and analyzes time series with user-specified parameters, thereby demonstrating how the accuracy of period and phase estimation depends on the type and level of noise, sampling rate, length of recording, and method. We demonstrate the potential uses of the apps through 2 in silico case studies.

An in-depth understanding of epithelial breast cell responses to the growth-promoting ligands is required to elucidate how the microenvironment (ME) signals affect cell-intrinsic regulatory networks and the cellular phenotypes they control, such as cell growth, progression, and differentiation. This is particularly important in understanding the mechanisms of breast cancer initiation and progression. However, the current mechanisms by which the ME signals influence these cellular phenotypes are not well established. To fill this gap, we developed a high-order correlation method using proteomics data to reveal the regulatory dynamics among proteins, histones, and six growth-promoting ligands in the MCF10 cell line. In the proposed method, the protein-ligand and histone-ligand correlations at multiple time points are first encoded in two three-way tensors. Then, a non-negative tensor factorization model is used to capture and quantify the protein-ligand and histone-ligand correlations spanning all time points, followed by a partial least squares regression process to model the correlations between histones and proteins. Our method revealed the onset of specific protein-histone signatures in response to growth ligands contributing to distinct cellular phenotypes that are indicative of breast cancer initiation and progression.

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