An Efficient Network Motif Discovery Approach for Co-Regulatory Networks

Co-regulatory networks, which consist of transcription factors (TFs), micro ribose nucleic acids (miRNAs), and target genes, have provided new insight into biological processes, revealing complicated and comprehensive regulatory relationships between biomolecules. To uncover the key co-regulatory mechanisms between these biomolecules, the identification of co-regulatory motifs has become beneficial. However, due to high-computational complexity, it is a hard task to identify co-regulatory network motifs with more than four interacting nodes in large-scale co-regulatory networks. To overcome this limitation, we propose an efficient algorithm, named large co-regulatory network motif (LCNM), to detect large co-regulatory network motifs. This algorithm is able to store a set of co-regulatory network motifs within a $G$ -tries structure. Moreover, we propose two ways to generate candidate motifs. For three- or four-interacting-node motifs, LCNM is able to generate all different types of motif through an enumeration method. For larger network motifs, we adopt a sampling method to generate candidate co-regulatory motifs. The experimental results demonstrate that LCNM cannot only improve the computational performance in exhaustive identification of all of the three- or four-node motifs but can also identify co-regulatory network motifs with a maximum of eight nodes. In addition, we implement a parallel version of our LCNM algorithm to further accelerate the motif detection process.

[1]  F. Schreiber,et al.  MODA: an efficient algorithm for network motif discovery in biological networks. , 2009, Genes & genetic systems.

[2]  R. Agami,et al.  Methylation-mediated silencing and tumour suppressive function of hsa-miR-124 in cervical cancer , 2010, Molecular Cancer.

[3]  Y. Liu,et al.  Association between miR-137 polymorphism and risk of schizophrenia: a meta-analysis. , 2016, Genetics and molecular research : GMR.

[4]  Aniruddha Datta,et al.  Using Boolean Logic Modeling of Gene Regulatory Networks to Exploit the Links Between Cancer and Metabolism for Therapeutic Purposes , 2016, IEEE Journal of Biomedical and Health Informatics.

[5]  Edwin Cheung,et al.  A transcriptional repressor co‐regulatory network governing androgen response in prostate cancers , 2012, The EMBO journal.

[6]  Fernando M. A. Silva,et al.  Querying subgraph sets with g-tries , 2012, DBSocial '12.

[7]  Xiang Li,et al.  Identification of active transcription factor and miRNA regulatory pathways in Alzheimer's disease , 2013, Bioinform..

[8]  Zengyou He,et al.  Reinforce: An Ensemble Approach for Inferring PPI Network from AP-MS Data , 2019, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[9]  Wenan Tan,et al.  Learning and identifying the crucial proteins in signal transduction networks by a novel method , 2014, 2014 9th International Conference on Computer Science & Education.

[10]  Meng Liu,et al.  MicroRNA-137 Inhibits EFNB2 Expression Affected by a Genetic Variant and Is Expressed Aberrantly in Peripheral Blood of Schizophrenia Patients , 2016, EBioMedicine.

[11]  Andrew Stranieri,et al.  A heuristic gene regulatory networks model for cardiac function and pathology , 2016, 2016 Computing in Cardiology Conference (CinC).

[12]  Fang-Xiang Wu,et al.  United Complex Centrality for Identification of Essential Proteins from PPI Networks , 2017, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[13]  S. Shen-Orr,et al.  Network motifs: simple building blocks of complex networks. , 2002, Science.

[14]  Sebastian Wernicke,et al.  Efficient Detection of Network Motifs , 2006, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[15]  Sayan Mukherjee,et al.  Sustained-input switches for transcription factors and microRNAs are central building blocks of eukaryotic gene circuits , 2013, Genome Biology.

[16]  Yaohang Li,et al.  MGT-SM: A Method for Constructing Cellular Signal Transduction Networks , 2019, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[17]  Joshua A. Grochow,et al.  Network Motif Discovery Using Subgraph Enumeration and Symmetry-Breaking , 2007, RECOMB.

[18]  Cüneyt Güzeliş,et al.  Aggregation for Computing Multi-Modal Stationary Distributions in 1-D Gene Regulatory Networks , 2018, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[19]  Pedro Ribeiro,et al.  Efficient and Scalable Algorithms for Network Motifs Discovery , 2011 .

[20]  Cheng Liang,et al.  Predicting MicroRNA-Disease Associations Using Kronecker Regularized Least Squares Based on Heterogeneous Omics Data , 2017, IEEE Access.

[21]  L. Dagum,et al.  OpenMP: an industry standard API for shared-memory programming , 1998 .

[22]  Frédérick A. Mallette,et al.  miR-137 Modulates a Tumor Suppressor Network-Inducing Senescence in Pancreatic Cancer Cells. , 2016, Cell reports.

[23]  Jiawei Luo,et al.  Discovery of microRNAs and Transcription Factors Co-Regulatory Modules by Integrating Multiple Types of Genomic Data , 2017, IEEE Transactions on NanoBioscience.

[24]  Cheng Liang,et al.  Predicting MicroRNA-Disease Associations Using Network Topological Similarity Based on DeepWalk , 2017, IEEE Access.

[25]  Fernando M. A. Silva,et al.  Discovering Colored Network Motifs , 2014, CompleNet.

[26]  Sebastian Wernicke,et al.  FANMOD: a tool for fast network motif detection , 2006, Bioinform..

[27]  Cheng Liang,et al.  A graph regularized non-negative matrix factorization method for identifying microRNA-disease associations , 2018, Bioinform..

[28]  Bin Hu,et al.  Modular reconfiguration of metabolic brain networks in health and cancer: A resting-state PET study , 2016, 2016 IEEE International Conference on Bioinformatics and Biomedicine (BIBM).

[29]  Fernando M. A. Silva,et al.  Efficient Parallel Subgraph Counting Using G-Tries , 2010, 2010 IEEE International Conference on Cluster Computing.

[30]  Brendan D. McKay,et al.  Practical graph isomorphism, II , 2013, J. Symb. Comput..

[31]  Zhongming Zhao,et al.  Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma , 2012, PLoS Comput. Biol..

[32]  Cheng Liang,et al.  A novel motif-discovery algorithm to identify co-regulatory motifs in large transcription factor and microRNA co-regulatory networks in human , 2015, Bioinform..

[33]  An-Yuan Guo,et al.  MicroRNA and transcription factor co-regulatory network analysis reveals miR-19 inhibits CYLD in T-cell acute lymphoblastic leukemia , 2012, Nucleic acids research.

[34]  Cheng Liang,et al.  A Novel Group Wise-Based Method for Calculating Human miRNA Functional Similarity , 2017, IEEE Access.