### Start from here

First line as headers, second line as time pints

Replicates are allowed with the same time points markers as the second line

Please check if files are read in correctly after upload.

Sample files for download (right click to save as): sample data for circadian;

### Upload data matrix (tsv/csv)

##### First column as row names

##### First line as column/experiment header, Second line as time point(replicates allowed)

### sample plot from choosen dataset

### First round of filtering on Original Data Table

"Search box" on the right corner is a quick global row selection tool on row names.

Use the column visibility button to deal with table of many columns.

### Further filtering:

Loading, please wait ...

### Analysis Setting

This app is a wrapper of meta2d {MetaCycle} |

## Detect rhythmic signals from time-series datasets with multiple methods

### Description

This is a function that incorporates ARSER, JTK_CYCLE and Lomb-Scargle to detect rhythmic signals from time-series datasets.

### Details

ARSER(Yang, 2010), JTK_CYCLE( Hughes, 2010), and Lomb-Scargle(Glynn, 2006) are three popular methods of detecting rhythmic signals. ARS can not analyze unevenly sampled datasets, or evenly sampled datasets but with missing values, or with replicate samples, or with non-integer sampling interval. JTK is not suitable to analyze unevenly sampled datasets or evenly sampled datasets but with non-integer sampling interval. If setanalysisStrategy as "auto"(default), meta2d will automatically select proper method from cycMethod for each input dataset. If the user clearly know that the dataset could be analyzed by each method defined bycycMethod and do not hope to output integrated values, analysisStrategy can be set as "selfUSE".

ARS used here is translated from its python version which always uses "yule-walker", "burg", and "mle"methods(see ar) to fit autoregressive models to time-series data. Fitting by "mle" will be very slow for datasets with many time points. If ARSmle = "auto" is used, meta2d will only include "mle" when number of time points is smaller than 24. In addition, one evaluation work(Wu, 2014) indicates that ARS shows relative high false positive rate in analyzing high-resolution datasets (1h/2days and 2h/2days). JTK(version 3) used here is the latest version, which improves its p-value calculation in analyzing datasets with missing values.

The power of detecting rhythmic signals for an algorithm is associated with the nature of data and interested periodic pattern(Deckard, 2013), which indicates that integrating analysis results from multiple methods may be helpful to rhythmic detection. For integrating p-values, Bonferroni correction("bonferroni") and Fisher's method("fisher") (Fisher, 1925; implementation code from MADAM) could be selected, and "bonferroni" is usually more conservative than "fisher". The integrated period is arithmetic mean of multiple periods. For integrating phase, meta2d takes use of mean of circular quantities. Integrated period and phase is further used to calculate the baseline value and amplitude through fitting a constructed periodic model.

Phases given by JTK and LS need to be adjusted with their predicted period (adjustedPhase = "predictedPer") before integration. If adjustedPhas = "notAdjusted" is selected, no integrated phase will be calculated. If set weightedPerPha as TRUE, weighted scores will be used in averaging periods and phases. Weighted scores for one method are based on all its reported p-values, which means a weighted score assigned to any one profile will be affected by all other profiles. It is always a problem of averaging phases with quite different period lengths(eg. averaging two phases with 16-hours' and 30-hours' period length). Currently, settingminper, maxper and ARSdefaultPer to a same value may be the only way of completely eliminating such problem.

This function is originally aimed to analyze large scale periodic data( eg. circadian transcriptome data) without individual information. Please pay attention to data format of input file(see Examples part). Except the first column and first row, others are time-series experimental values(setting missing values as NA).

### References

Yang R. and Su Z. (2010). Analyzing circadian expression data by harmonic regression based on autoregressive spectral estimation. *Bioinformatics*, **26(12)**, i168–i174.

Hughes M. E., Hogenesch J. B. and Kornacker K. (2010). JTK_CYCLE: an efficient nonparametric algorithm for detecting rhythmic components in genome-scale data sets. *Journal of Biological Rhythms*, **25(5)**, 372–380.

Glynn E. F., Chen J. and Mushegian A. R. (2006). Detecting periodic patterns in unevenly spaced gene expression time series using Lomb-Scargle periodograms. *Bioinformatics*, **22(3)**, 310–316.

Wu G., Zhu J., Yu J., Zhou L., Huang J. Z. and Zhang Z. (2014). Evaluation of five methods for genome-wide circadian gene identification. *Journal of Biological Rhythms*, **29(4)**, 231–242.

Deckard A., Anafi R. C., Hogenesch J. B., Haase S.B. and Harer J. (2013). Design and analysis of large-scale biological rhythm studies: a comparison of algorithms for detecting periodic signals in biological data.*Bioinformatics*, **29(24)**, 3174–3180.

Fisher, R.A. (1925). *Statistical methods for research workers*. Oliver and Boyd (Edinburgh).

Kugler K. G., Mueller L.A. and Graber A. (2010). MADAM - an open source toolbox for meta-analysis. *Source Code for Biology and Medicine*, **5**, 3.

Analyzing, please wait ...

### correlation matrix

### boxplot with jitter

### Denisty plot

### Circadian Analysis

#### Refernces:

JTK_CycleMetaCycle: an integrated R package to evaluate periodicity in large scale data

MetaCycle Manual

### Contact

### Change log

V0.1: 20171006,online