BACKGROUND: Public Data Commons (PDC) have been highlighted in the scientific literature for their capacity to collect and harmonize big data. On the other hand, local data commons (LDC), located within an institution or organization, have been underrepresented in the scientific literature, even though they are a critical part of research infrastructure. Being closest to the sources of data, LDCs provide the ability to collect and maintain the most up-to-date, high-quality data within an organization, closest to the sources of the data. As a data provider, LDCs have many challenges in both collecting and standardizing data, moreover, as a consumer of PDC, they face problems of data harmonization stemming from the monolithic harmonization pipeline designs commonly adapted by many PDCs. Unfortunately, existing guidelines and resources for building and maintaining data commons exclusively focus on PDC and provide very little information on LDC. RESULTS: This article focuses on four important observations. First, there are three different types of LDC service models that are defined based on their roles and requirements. These can be used as guidelines for building new LDC or enhancing the services of existing LDC. Second, the seven core services of LDC are discussed, including cohort identification and facilitation of genomic sequencing, the management of molecular reports and associated infrastructure, quality control, data harmonization, data integration, data sharing, and data access control. Third, instead of commonly developed monolithic systems, we propose a new data sharing method for data harmonization that combines both divide-and-conquer and bottom-up approaches. Finally, an end-to-end LDC implementation is introduced with real-world examples. CONCLUSIONS: Although LDCs are an optimal place to identify and address data quality issues, they have traditionally been relegated to the role of passive data provider for much larger PDC. Indeed, many LDCs limit their functions to only conducting routine data storage and transmission tasks due to a lack of information on how to design, develop, and improve their services using limited resources. We hope that this work will be the first small step in raising awareness among the LDCs of their expanded utility and to publicize to a wider audience the importance of LDC.

Identifying functionally similar or closely related genes and gene products has significant impacts on biological and clinical studies as well as drug discovery. In this paper, we propose an effective and practically useful method measuring both gene and gene product similarity by integrating the topology of gene ontology, known functional domains and their functional annotations. The proposed method is comprehensively evaluated through statistical analysis of the similarities derived from sequence, structure and phylogenetic profiles, and clustering analysis of disease genes clusters. Our results show that the proposed method clearly outperforms other conventional methods. Furthermore, literature analysis also reveals that the proposed method is both statistically and biologically promising for identifying functionally similar genes or gene products. In particular, we demonstrate that the proposed functional similarity metric is capable of discoverying new disease related genes or gene products.

Defining semantic functional similarity measures provides effective means to validate protein function prediction methods and to retrieve biologically relevant information from big biological data. It also improves understanding of interrelationship between genes and gene products (GPs). Currently, one of the most commonly used tools for functionally annotating genes and GPs is the Gene Ontology (GO), which describes genes/GPs using a machine-readable language. To measure the semantic similarity between two GO terms, many studies that are based on GO topology have recently been reported. However, a comprehensive assessment and general guidelines for validating these methods are lacking. In this paper, we collect a large dataset to evaluate five often-used semantic similarity measure methods by estimating sequence similarity, phylogenetic profile similarity, and structural similarity. We further compare the measures in terms of their clustering performance using domains extracted from SCOP database. We describe some key aspects of these measure methods and discuss how the limitations may be addressed as well as some open problems.

While genome sequencing projects have generated tremendous amounts of protein sequence data for a vast number of genomes, substantial portions of most genomes are still unannotated. Despite the success of experimental methods for identifying protein functions, they are often lab intensive and time consuming. Thus, it is only practical to use in silico methods for the genome-wide functional annotations. In this paper, we propose new features extracted from protein sequence only and machine learning-based methods for computational function prediction. These features are derived from a position-specific scoring matrix, which has shown great potential in other bininformatics problems. We evaluate these features using four different classifiers and yeast protein data. Our experimental results show that features derived from the position-specific scoring matrix are appropriate for automatic function annotation.

MOTIVATION: Identification of protein interaction sites has significant impact on understanding protein function, elucidating signal transduction networks and drug design studies. With the exponentially growing protein sequence data, predictive methods using sequence information only for protein interaction site prediction have drawn increasing interest. In this article, we propose a predictive model for identifying protein interaction sites. Without using any structure data, the proposed method extracts a wide range of features from protein sequences. A random forest-based integrative model is developed to effectively utilize these features and to deal with the imbalanced data classification problem commonly encountered in binding site predictions. RESULTS: We evaluate the predictive method using 2829 interface residues and 24,616 non-interface residues extracted from 99 polypeptide chains in the Protein Data Bank. The experimental results show that the proposed method performs significantly better than two other sequence-based predictive methods and can reliably predict residues involved in protein interaction sites. Furthermore, we apply the method to predict interaction sites and to construct three protein complexes: the DnaK molecular chaperone system, 1YUW and 1DKG, which provide new insight into the sequence-function relationship. We show that the predicted interaction sites can be valuable as a first approach for guiding experimental methods investigating protein-protein interactions and localizing the specific interface residues. AVAILABILITY: Datasets and software are available at http://ittc.ku.edu/~xwchen/bindingsite/prediction.

We address feature selection problems for classification of small samples and high dimensionality. A practical example is microarray-based cancer classification problems, where sample size is typically less than 100 and number of features is several thousands or higher. One of the commonly used methods in addressing this problem is recursive feature elimination (RFE) method, which utilizes the generalization capability embedded in support vector machines and is thus suitable for small samples problems. We propose a novel method using minimum reference set (MRS) generated by the nearest neighbor rule. MRS is the set of minimum number of samples that correctly classify all the training samples. It is related to structural risk minimization principle and thus leads to good generalization. The proposed MRS based method is compared to RFE method with several real datasets, and experimental results show that the MRS method produces better classification performance.

For classification with small training samples and high dimensionality, feature selection plays an important role in avoiding overfitting problems and improving classification performance. One of the commonly used feature selection methods for small samples problems is recursive feature elimination (RFE) method. RFE method utilizes the generalization capability embedded in support vector machines and is thus suitable for small samples problems. Despite its good performance, RFE tends to discard "weak" features, which may provide a significant improvement of performance when combined with other features. In this paper, we propose an enhanced recursive feature elimination (EnRFE) method for feature selection in small training sample classification. Our experimental results show that the proposed method outperforms the original RFE in terms of classification accuracy on various datasets.