A Cheminformatic Toolkit for Mining Biomedical Knowledge

Rosania, Gus R.; Crippen, Gordon M.; Woolf, Peter J.; States, David J.; Shedden, Kerby

doi:10.1007/s11095-007-9285-5

Cited by 25 publications

(12 citation statements)

References 192 publications

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“…The comprehensive information of small molecules and their biological activities in PubChem brings great opportunities for academic researchers in the chemical biology, medicinal chemistry and cheminformatics fields (Oprea et al ., 2007; Ovaa and van Leeuwen, 2008; Rosania et al ., 2007; Southan et al ., 2007) to access and utilize large scale biological activity data to meet their research goals. Several groups have attempted to develop methods to analyze the data in this database (Guha and Schurer, 2008; Han et al ., 2008; Hur and Wild, 2008; Nakai et al ., 2009; Xie and Chen, 2008).…”

Section: Introductionmentioning

confidence: 99%

A novel method for mining highly imbalanced high-throughput screening data in PubChem

Wang

Bryant

2009

Bioinformatics

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Motivation: The comprehensive information of small molecules and their biological activities in PubChem brings great opportunities for academic researchers. However, mining high-throughput screening (HTS) assay data remains a great challenge given the very large data volume and the highly imbalanced nature with only small number of active compounds compared to inactive compounds. Therefore, there is currently a need for better strategies to work with HTS assay data. Moreover, as luciferase-based HTS technology is frequently exploited in the assays deposited in PubChem, constructing a computational model to distinguish and filter out potential interference compounds for these assays is another motivation.Results: We used the granular support vector machines (SVMs) repetitive under sampling method (GSVM-RU) to construct an SVM from luciferase inhibition bioassay data that the imbalance ratio of active/inactive is high (1/377). The best model recognized the active and inactive compounds at the accuracies of 86.60% and 88.89 with a total accuracy of 87.74%, by cross-validation test and blind test. These results demonstrate the robustness of the model in handling the intrinsic imbalance problem in HTS data and it can be used as a virtual screening tool to identify potential interference compounds in luciferase-based HTS experiments. Additionally, this method has also proved computationally efficient by greatly reducing the computational cost and can be easily adopted in the analysis of HTS data for other biological systems.Availability: Data are publicly available in PubChem with AIDs of 773, 1006 and 1379.Contact: ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.govSupplementary information: Supplementary data are available at Bioinformatics online.

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Section: Introductionmentioning

confidence: 99%

A novel method for mining highly imbalanced high-throughput screening data in PubChem

Wang

Bryant

2009

Bioinformatics

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“…These authors found that 32% of the GNF compounds could be linked to other databases by PubChem. Rosania et al reviewed the current cheminformatic tools available to mine biomedical knowledge, and the challenges involved to implement these tools for users who do not have extensive training in cheminformatics [8]. Ingsriswang and Pacharawongsakda developed a web based tool known as sMOL Explorer [9].…”

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confidence: 99%

Data mining PubChem using a support vector machine with the Signature molecular descriptor: Classification of factor XIa inhibitors

Weis

Visco

Faulon

2008

Journal of Molecular Graphics and Modelling

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“…Following advances in location proteomics 104–108 , machine vision-based quantitative image analysis has been used to establish the degree of co-localization between compounds of interest with an organelle-specific reference marker 109–111 . Furthermore, large combinatorial libraries of fluorescent probes and automated high content screening instruments have facilitated analysis of chemical motifs associated with specific intracellular distribution patterns 110–112 . More recently, fluorescence resonance energy transfer has been used to study the trafficking and distribution of xenobiotics 113 .…”

Section: Whole Cell Based Microscopic Imaging Studies As Evidence Formentioning

confidence: 99%

The Subcellular Distribution of Small Molecules: From Pharmacokinetics to Synthetic Biology

et al. 2011

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The systemic pharmacokinetics and pharmacodynamics of small molecules are determined by subcellular transport phenomena. Although approaches used to study the subcellular distribution of small molecules have gradually evolved over the past several decades, experimental analysis and prediction of cellular pharmacokinetics remains a challenge. In this article, we surveyed the progress of subcellular distribution research since the 1960s, with a focus on the advantages, disadvantages and limitations of the various experimental techniques. Critical review of the existing body of knowledge pointed to many opportunities to advance the rational design of organelle-targeted chemical agents. These opportunities include: 1) development of quantitative, nonfluorescence-based, whole cell methods and techniques to measure the subcellular distribution of chemical agents in multiple compartments; 2) exploratory experimentation with nonspecific transport probes that have not been enriched with putative, organelle-targeting features; 3) elaboration of hypothesis-driven, mechanistic and modeling-based approaches to guide experiments aimed at elucidating subcellular distribution and transport; and 4) introduction of revolutionary conceptual approaches borrowed from the field of synthetic biology combined with cutting edge experimental strategies. In our laboratory, state-of-the-art subcellular transport studies are now being aimed at understanding the formation of new intracellular membrane structures in response to drug therapy, exploring the function of drug-membrane complexes as intracellular drug depots, and synthesizing new organelles with extraordinary physical and chemical properties.

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A Cheminformatic Toolkit for Mining Biomedical Knowledge

Cited by 25 publications

References 192 publications

A novel method for mining highly imbalanced high-throughput screening data in PubChem

A novel method for mining highly imbalanced high-throughput screening data in PubChem

Data mining PubChem using a support vector machine with the Signature molecular descriptor: Classification of factor XIa inhibitors

The Subcellular Distribution of Small Molecules: From Pharmacokinetics to Synthetic Biology

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