Loregic: A Method to Characterize the Cooperative Logic of Regulatory Factors

Daifeng Wang, Koon-Kiu Yan, Cristina Sisu, Chao Cheng, Joel S. Rozowsky, William Meyerson, Mark B. Gerstein

Abstract: Author Summary Gene expression is controlled by various gene regulatory factors. Those factors work cooperatively forming a complex regulatory circuit genome wide. Corruptions of regulatory cooperativity may lead to abnormal gene expression activity such as cancer. Traditional experimental methods, however, can only identify small-scale regulatory activity. Thus, to systematically understand the cooperativity between and among different types of regulatory factors, we need the efficient and systematic computational methods. Regulatory circuits have been suggested to behave analogously to the electronic circuits in which a wide variety of electronic elements work coordinately to function correctly. Recently, an increasing amount of next generation sequencing data provides a great resource to study regulatory activity. Thus, we developed a general-purpose computational method using logic-circuit models from electronics and applied it to a human leukemia dataset, identifying the genome-wide cooperativity of transcription factors and microRNAs.