title: Finding pathway-modulating genes from a novel Ontology Fingerprint-derived gene network.
abstract: To enhance our knowledge regarding biological pathway regulation, we took an integrated approach, using the biomedical literature, ontologies, network analyses and experimental investigation to infer novel genes that could modulate biological pathways. We first constructed a novel gene network via a pairwise comparison of all yeast genes' Ontology Fingerprints--a set of Gene Ontology terms overrepresented in the PubMed abstracts linked to a gene along with those terms' corresponding enrichment P-values. The network was further refined using a Bayesian hierarchical model to identify novel genes that could potentially influence the pathway activities. We applied this method to the sphingolipid pathway in yeast and found that many top-ranked genes indeed displayed altered sphingolipid pathway functions, initially measured by their sensitivity to myriocin, an inhibitor of de novo sphingolipid biosynthesis. Further experiments confirmed the modulation of the sphingolipid pathway by one of these genes, PFA4, encoding a palmitoyl transferase. Comparative analysis showed that few of these novel genes could be discovered by other existing methods. Our novel gene network provides a unique and comprehensive resource to study pathway modulations and systems biology in general.
authors: Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Tingting
authors: T
authors: Qin
authors: The Stony Brook University Cancer Center and the Department of Medicine, Stony Brook, NY 11794, USA.
authors: Nabil
authors: N
authors: Matmati
authors: Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Lam C
authors: LC
authors: Tsoi
authors: Department of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Bidyut K
authors: BK
authors: Mohanty
authors: Department of Computer Science and Engineering, University of South Carolina, Columbia, SC 29208, USA.
authors: Nan
authors: N
authors: Gao
authors: Department of Computer Science and Engineering, University of South Carolina, Columbia, SC 29208, USA Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Tianjin, China.
authors: Jijun
authors: J
authors: Tang
authors: Department of Public Health Science, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Andrew B
authors: AB
authors: Lawson
authors: The Stony Brook University Cancer Center and the Department of Medicine, Stony Brook, NY 11794, USA.
authors: Yusuf A
authors: YA
authors: Hannun
authors: School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA wenjin.j.zheng@uth.tmc.edu.
authors: W Jim
authors: WJ
authors: Zheng
mesh_terms: D001499:Bayes Theorem; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D005800:Genes, Fungal; D053858:Metabolic Networks and Pathways / Q000235:genetics; D039781:PubMed; D013107:Sphingolipids / Q000378:metabolism; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
chemical_list: D013107:Sphingolipids