Methods of identifying cis-regulatory elements and uses thereof

A method of determining a clusters of genomic regions (COGR) signature, optionally a Clusters of cis-Regulatory Elements (CORE) signature in a biological sample, the method comprising:

• obtaining a chromatin profile of genomic DNA of the biological sample;
• identifying two or more individual cis-regulatory elements (CREs) in the chromatin profile;
• and
• locating one or more COGRs optionally COREs, to generate a COGR signature, optionally a CORE signature, comprising the steps of:
• i) grouping different numbers of neighboring individual CREs throughout the genome and categorizing the groups according to order (O) which is the number of neighboring individual CREs in the groups;
• ii) identifying a maximum window size (MWS) by estimating a distribution of window sizes for each order O based on a maximum distance between the individual CREs in all groups of that order O within the chromatin profile and calculating the MWS according to the following:
• a) MWS=Q1(log(WS))−1.5*IQ(log(WS)), where Q1(log(WS)) and IQ(log(WS)) are first quartile and interquartile distributions of window sizes of that order O, respectively;
• or
• b) MWS=Q1(log(WSnormalized))−1.5*IQ(log(WSnormalized)) where
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• identifying a maximum O (Omax), defined as a value of given order O at which an increase in the given order O does not result in an increase in the MWS for the given order O;
• iii) identifying potential COGRs, optionally potential COREs, by calling groups of CREs of a particular order O with a window size less than the MWS for the particular order O as the potential COGRs, optionally the potential COREs, for each order O from Omax to O=2;
• and
• iv) for each order O from O=2 to Omax, calculating the change in (MWS-median(WS))/median(WS), where WS is a distribution of maximum distance between individual CREs within the potential COGRs, optionally the potential COREs, of that order and filtering out lower order potential COGRs, optionally potential CORES up to a point where (MWS-median(WS))/median(WS) decreases with increasing order O, and any remaining potential COGRs, optionally potential COREs, are identified as actual COGRs, optionally actual COREs, and included in the COGR signature, optionally the CORE signature.