title: StemCellCKB: An Integrated Stem Cell-Specific Chemogenomics KnowledgeBase for Target Identification and Systems-Pharmacology Research.
abstract: Given the capacity of self-renewal and multilineage differentiation, stem cells are promising sources for use in regenerative medicines as well as in the clinical treatment of certain hematological malignancies and degenerative diseases. Complex networks of cellular signaling pathways largely determine stem cell fate and function. Small molecules that modulate these pathways can provide important biological and pharmacological insights. However, it is still challenging to identify the specific protein targets of these compounds, to explore the changes in stem cell phenotypes induced by compound treatment and to ascertain compound mechanisms of action. To facilitate stem cell related small molecule study and provide a better understanding of the associated signaling pathways, we have constructed a comprehensive domain-specific chemogenomics resource, called StemCellCKB ( http://www.cbligand.org/StemCellCKB/ ). This new cloud-computing platform describes the chemical molecules, genes, proteins, and signaling pathways implicated in stem cell regulation. StemCellCKB is also implemented with web applications designed specifically to aid in the identification of stem cell relevant protein targets, including TargetHunter, a machine-learning algorithm for predicting small molecule targets based on molecular fingerprints, and HTDocking, a high-throughput docking module for target prediction and systems-pharmacology analyses. We have systematically tested StemCellCKB to verify data integrity. Target-prediction accuracy has also been validated against the reported known target/compound associations. This proof-of-concept example demonstrates that StemCellCKB can (1) accurately predict the macromolecular targets of existing stem cell modulators and (2) identify novel small molecules capable of probing stem cell signaling mechanisms, for use in systems-pharmacology studies. StemCellCKB facilitates the exploration and exchange of stem cell chemogenomics data among members of the broader research community.
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy; National Center of Excellence for Computational Drug Abuse Research; Drug Discovery Institute; Departments of Computational Biology and Structural Biology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.|Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300020, P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy; National Center of Excellence for Computational Drug Abuse Research; Drug Discovery Institute; Departments of Computational Biology and Structural Biology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Lirong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy; National Center of Excellence for Computational Drug Abuse Research; Drug Discovery Institute; Departments of Computational Biology and Structural Biology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy; National Center of Excellence for Computational Drug Abuse Research; Drug Discovery Institute; Departments of Computational Biology and Structural Biology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Haizi
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy; National Center of Excellence for Computational Drug Abuse Research; Drug Discovery Institute; Departments of Computational Biology and Structural Biology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Terence Francis
authors.initials: TF
authors.lastname: McGuire
authors.affiliation: Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300020, P. R. China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300020, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin 300020, P. R. China.
authors.forename: Yingdai
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy; National Center of Excellence for Computational Drug Abuse Research; Drug Discovery Institute; Departments of Computational Biology and Structural Biology, School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Xiang-Qun
authors.initials: XQ
authors.lastname: Xie
mesh_terms: D000067917:Cloud Computing; D019295:Computational Biology / Q000379:methods*; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D051188:Knowledge Bases; D008958:Models, Molecular; D060066:Protein Interaction Maps / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism