title: Noise propagation with interlinked feed-forward pathways.
abstract: Functionally similar pathways are often seen in biological systems, forming feed-forward controls. The robustness in network motifs such as feed-forward loops (FFLs) has been reported previously. In this work, we studied noise propagation in a development network that has multiple interlinked FFLs. A FFL has the potential of asymmetric noise-filtering (i.e., it works at either the "ON" or the "OFF" state in the target gene). With multiple, interlinked FFLs, we show that the propagated noises are largely filtered regardless of the states in the input genes. The noise-filtering property of an interlinked FFL can be largely derived from that of the individual FFLs, and with interlinked FFLs, it is possible to filter noises in both "ON" and "OFF" states in the output. We demonstrated the noise filtering effect in the developmental regulatory network of Caenorhabditis elegans that controls the timing of distal tip cell (DTC) migration. The roles of positive feedback loops involving blmp-1 and the degradation regulation of DRE-1 also studied. Our analyses allow for better inference from network structures to noise-filtering properties, and provide insights into the mechanisms behind the precise DTC migration controls in space and time.
authors.affiliation: Bioinformatics Program, Taiwan International Graduate Program, Institute of Information Science, Academia Sinica, Taipei, Taiwan.|Institute of Chemistry, Academia Sinica, Taipei, Taiwan.|Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Surendhar Reddy
authors.initials: SR
authors.lastname: Chepyala
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei, Taiwan.|Department of Chemistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Ching-Cher Sanders
authors.initials: CC
authors.lastname: Yan
authors.affiliation: Department of Chemistry, National Taiwan University, Taipei, Taiwan.
authors.forename: Chun-Yi David
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Genome and Systems Biology program, National Taiwan University, Taipei, Taiwan.|Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan.|Department of Life Science, National Taiwan University, Taipei, Taiwan.|Center for Systems Biology, National Taiwan University, Taipei, Taiwan.|Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Wu
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei, Taiwan.|Genome and Systems Biology program, National Taiwan University, Taipei, Taiwan.
authors.forename: Chao-Ping
authors.initials: CP
authors.lastname: Hsu
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D003198:Computer Simulation; D044783:F-Box Proteins / Q000235:genetics* / Q000378:metabolism; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D055550:Protein Stability; D059748:Proteolysis; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C519094:DRE-1 protein, C elegans; D044783:F-Box Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C000600050:blmp-1 protein, C elegans