دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Loregic: A Method to Characterize the Cooperative Logic of Regulatory Factors
المؤلفون: Yan, K-K, Sisu, C, Cheng, C, Rozowsky, J, Meyerson, W, Gerstein, MB
بيانات النشر: PUBLIC LIBRARY SCIENCE
سنة النشر: 2015
المجموعة: Brunel University London: Brunel University Research Archive (BURA)
مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Biochemical Research Methods, Mathematical & Computational Biology, Biochemistry & Molecular Biology, CELL-CYCLE, SACCHAROMYCES-CEREVISIAE, TRANSCRIPTION FACTORS, GENOMIC ANALYSIS, GENE-EXPRESSION, BOOLEAN LOGIC, C-MYC, NETWORKS, IDENTIFICATION, BINDING
الوصف: The topology of the gene-regulatory network has been extensively analyzed. Now, given the large amount of available functional genomic data, it is possible to go beyond this and systematically study regulatory circuits in terms of logic elements. To this end, we present Loregic, a computational method integrating gene expression and regulatory network data, to characterize the cooperativity of regulatory factors. Loregic uses all 16 possible twoinput- one-output logic gates (e.g. AND or XOR) to describe triplets of two factors regulating a common target. We attempt to find the gate that best matches each triplet’s observed gene expression pattern across many conditions. We make Loregic available as a generalpurpose tool (github.com/gersteinlab/loregic). We validate it with known yeast transcriptionfactor knockout experiments. Next, using human ENCODE ChIP-Seq and TCGA RNA-Seq data, we are able to demonstrate how Loregic characterizes complex circuits involving both proximally and distally regulating transcription factors (TFs) and also miRNAs. Furthermore, we show that MYC, a well-known oncogenic driving TF, can be modeled as acting independently from other TFs (e.g., using OR gates) but antagonistically with repressing miRNAs. Finally, we inter-relate Loregic’s gate logic with other aspects of regulation, such as indirect binding via protein-protein interactions, feed-forward loop motifs and global regulatory hierarchy.
نوع الوثيقة: article in journal/newspaper
وصف الملف: ? - ? (21)
اللغة: English
تدمد: 1553-734X
1553-7358
العلاقة: PLOS COMPUTATIONAL BIOLOGY; PLOS COMPUTATIONAL BIOLOGY, 2015, 11 (4), pp. ? - ? (21); http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000354517600015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=f12c8c83318cf2733e615e54d9ed7ad5Test; ARTN e1004132; http://bura.brunel.ac.uk/handle/2438/14906Test; http://dx.doi.org/10.1371/journal.pcbi.1004132Test
DOI: 10.1371/journal.pcbi.1004132
الإتاحة: https://doi.org/10.1371/journal.pcbi.1004132Test
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000354517600015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=f12c8c83318cf2733e615e54d9ed7ad5Test
http://bura.brunel.ac.uk/handle/2438/14906Test
رقم الانضمام: edsbas.D02D2C26
قاعدة البيانات: BASE
الوصف
تدمد:1553734X
15537358
DOI:10.1371/journal.pcbi.1004132