# Introduction

RAD is a webtool for analysing region associated differentially expressed genes. Visualization of DEGs surrounding peak regions are implemented in RAD in order to help researchers to infer the regulatory function of transcription factors or genomic sequence.

The algorithm behind RAD has been implemented in recent publications (Pastor et al., 2018; Harris et al., 2018; Gallego-Bartolomé et al., 2019). There are three main steps in the algorithm:

1. Infer region associated genes within specific distance using  awk  and  bedtools.
2.

3. A specific distance was split into different bins into which up/down-regulated genes are assigned. We calculated observed versus expected as follows to reduce false-positive rate:

4. Perform a hypergeometric test to calculate the p-value over the four elements above

k, up/down-regulated genes covered in different distance bins,
n, all genes covered in different distance bins,
m, up/down-regulated genes covered in region extended distance,
N, whole genome genes.

# Supported Reference Genome

Currently, RAD supports referenece genome of the well-annotated human (GRCh38/hg38 (EMSEMBL GRCh38, Dec. 2013) and GRCh37/hg19 (EMSEMBL GRCh37, Feb. 2009)), mouse (GRCm38/mm10 (ENSEMBL GRCm38, Dec. 2011) and NCBIm37 (NCBI build 37/mm9, Jul. 2007)), and Arabidopsis thaliana (EMSEMBL TAIR10, June. 2016).

We hope to gradually expand the set of genome data we support.

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# Citations

Here are some papers that cites RAD:

1. Pastor, W.A., Liu, W., Chen, D., Ho, J., Kim, R., Hunt, T.J., Lukianchikov, A., Liu, X., Polo, J.M., Jacobsen, S.E. & Clark, A.T. (2018) TFAP2C regulates transcription in human naive pluripotency by opening enhancers. Nature cell biology, 20, 553-564. doi: 10.1038/s41556-018-0089-0
2. Harris, C.J., Scheibe, M., Wongpalee, S.P., Liu, W., Cornett, E.M., Vaughan, R.M., Li, X., Chen, W., Xue, Y., Zhong, Z., Yen, L., Barshop, W.D., Rayatpisheh, S., Gallego-Bartolome, J., Groth, M., Wang, Z., Wohlschlegel, J.A., Du, J., Rothbart, S.B., Butter, F. & Jacobsen, S.E. (2018) A DNA methylation reader complex that enhances gene transcription. Science, 362, 1182-1186. doi: 10.1126/science.aar7854
3. Gallego-Bartolomé, J., Liu, W., Kuo, P.H., Feng, S., Ghoshal, B., Gardiner, J., Zhao, J.M., Park, S.Y., Chory, J. & Jacobsen, S.E. (2019) Co-targeting RNA Polymerases IV and V Promotes Efficient De Novo DNA Methylation in Arabidopsis. Cell, 176, 1068-1082.e19. doi: 10.1016/j.cell.2019.01.029

# Web Browsers

## Which browser is recommended for RAD?

We recommended Google Chrome. It offers the best compatibility and performance in our tests.