title: Predicting high-throughput screening results with scalable literature-based discovery methods.
abstract: The identification of new therapeutic uses for existing agents has been proposed as a means to mitigate the escalating cost of drug development. A common approach to such repurposing involves screening libraries of agents for activities against cell lines. In silico methods using knowledge from the biomedical literature have been proposed to constrain the costs of screening by identifying agents that are likely to be effective a priori. However, results obtained with these methods are seldom evaluated empirically. Conversely, screening experiments have been criticized for their inability to reveal the biological basis of their results. In this paper, we evaluate the ability of a scalable literature-based approach, discovery-by-analogy, to identify a small number of active agents within a large library screened for activity against prostate cancer cells. The methods used permit retrieval of the knowledge used to infer their predictions, providing a plausible biological basis for predicted activity.
authors.affiliation: University of Texas School of Biomedical Informatics at Houston, Houston, Texas, USA.
authors.forename: T
authors.initials: T
authors.lastname: Cohen
authors.affiliation: Microsoft Bing, Redmond, Washington, USA.
authors.forename: D
authors.initials: D
authors.lastname: Widdows
authors.affiliation: Center for Translational Cancer Research, Texas A&M Health Sciences Center, Institute of Biosciences and Technology, Houston, Texas, USA.
authors.forename: C
authors.initials: C
authors.lastname: Stephan
authors.affiliation: Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: R
authors.initials: R
authors.lastname: Zinner
authors.affiliation: Department of Genitourinary Medical Oncology, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: National Library of Medicine, Bethesda, Maryland, USA.
authors.forename: T
authors.initials: T
authors.lastname: Rindflesch
authors.affiliation: Center for Translational Cancer Research, Texas A&M Health Sciences Center, Institute of Biosciences and Technology, Houston, Texas, USA.
authors.forename: P
authors.initials: P
authors.lastname: Davies