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Biclustering of biologically meaningful binary information is essential in many applications related to drug discovery, like protein-protein interactions and gene expressions. However, for robust performance in recently emerging large health datasets, it is important for new biclustering algorithms to be scalable and fast. We present a rapid unsupervised biclustering (RUBic) algorithm that achieves this objective with a novel encoding and search strategy. RUBic significantly reduces the computational overhead on both synthetic and experimental datasets shows significant computational benefits, with respect to several state-of-the-art biclustering algorithms. In 100 synthetic binary datasets, our method took [Formula: see text] s to extract 494,872 biclusters. In the human PPI database of size [Formula: see text], our method generates 1840 biclusters in [Formula: see text] s. On a central nervous system embryonic tumor gene expression dataset of size 712,940, our algorithm takes   101 min to produce 747,069 biclusters, while the recent competing algorithms take significantly more time to produce the same result. RUBic is also evaluated on five different gene expression datasets and shows significant speed-up in execution time with respect to existing approaches to extract significant KEGG-enriched bi-clustering. RUBic can operate on two modes, base and flex, where base mode generates maximal biclusters and flex mode generates less number of clusters and faster based on their biological significance with respect to KEGG pathways. The code is available at ( https://github.com/CMATERJU-BIOINFO/RUBic ) for academic use only., (© 2023. The Author(s).)

Background: A considerable number of data mining approaches for biomedical data analysis, including state-of-the-art associative models, require a form of data discretization. Although diverse discretization approaches have been proposed, they generally work under a strict set of statistical assumptions which are arguably insufficient to handle the diversity and heterogeneity of clinical and molecular variables within a given dataset. In addition, although an increasing number of symbolic approaches in bioinformatics are able to assign multiple items to values occurring near discretization boundaries for superior robustness, there are no reference principles on how to perform multi-item discretizations., Results: In this study, an unsupervised discretization method, DI2, for variables with arbitrarily skewed distributions is proposed. Statistical tests applied to assess differences in performance confirm that DI2 generally outperforms well-established discretizations methods with statistical significance. Within classification tasks, DI2 displays either competitive or superior levels of predictive accuracy, particularly delineate for classifiers able to accommodate border values., Conclusions: This work proposes a new unsupervised method for data discretization, DI2, that takes into account the underlying data regularities, the presence of outlier values disrupting expected regularities, as well as the relevance of border values. DI2 is available at https://github.com/JupitersMight/DI2., (© 2021. The Author(s).)

Background: Machine learning involves strategies and algorithms that may assist bioinformatics analyses in terms of data mining and knowledge discovery. In several applications, viz. in Life Sciences, it is often more important to understand how a prediction was obtained rather than knowing what prediction was made. To this end so-called interpretable machine learning has been recently advocated. In this study, we implemented an interpretable machine learning package based on the rough set theory. An important aim of our work was provision of statistical properties of the models and their components., Results: We present the R.ROSETTA package, which is an R wrapper of ROSETTA framework. The original ROSETTA functions have been improved and adapted to the R programming environment. The package allows for building and analyzing non-linear interpretable machine learning models. R.ROSETTA gathers combinatorial statistics via rule-based modelling for accessible and transparent results, well-suited for adoption within the greater scientific community. The package also provides statistics and visualization tools that facilitate minimization of analysis bias and noise. The R.ROSETTA package is freely available at https://github.com/komorowskilab/R.ROSETTA . To illustrate the usage of the package, we applied it to a transcriptome dataset from an autism case-control study. Our tool provided hypotheses for potential co-predictive mechanisms among features that discerned phenotype classes. These co-predictors represented neurodevelopmental and autism-related genes., Conclusions: R.ROSETTA provides new insights for interpretable machine learning analyses and knowledge-based systems. We demonstrated that our package facilitated detection of dependencies for autism-related genes. Although the sample application of R.ROSETTA illustrates transcriptome data analysis, the package can be used to analyze any data organized in decision tables.

Background: Drug repositioning has been an important and efficient method for discovering new uses of known drugs. Researchers have been limited to one certain type of collaborative filtering (CF) models for drug repositioning, like the neighborhood based approaches which are good at mining the local information contained in few strong drug-disease associations, or the latent factor based models which are effectively capture the global information shared by a majority of drug-disease associations. Few researchers have combined these two types of CF models to derive a hybrid model which can offer the advantages of both. Besides, the cold start problem has always been a major challenge in the field of computational drug repositioning, which restricts the inference ability of relevant models., Results: Inspired by the memory network, we propose the hybrid attentional memory network (HAMN) model, a deep architecture combining two classes of CF models in a nonlinear manner. First, the memory unit and the attention mechanism are combined to generate a neighborhood contribution representation to capture the local structure of few strong drug-disease associations. Then a variant version of the autoencoder is used to extract the latent factor of drugs and diseases to capture the overall information shared by a majority of drug-disease associations. During this process, ancillary information of drugs and diseases can help alleviate the cold start problem. Finally, in the prediction stage, the neighborhood contribution representation is coupled with the drug latent factor and disease latent factor to produce predicted values. Comprehensive experimental results on two data sets demonstrate that our proposed HAMN model outperforms other comparison models based on the AUC, AUPR and HR indicators., Conclusions: Through the performance on two drug repositioning data sets, we believe that the HAMN model proposes a new solution to improve the prediction accuracy of drug-disease associations and give pharmaceutical personnel a new perspective to develop new drugs.

Background: Traditional approaches to elucidation of protein structures by Nuclear Magnetic Resonance spectroscopy (NMR) rely on distance restraints also known as Nuclear Overhauser effects (NOEs). The use of NOEs as the primary source of structure determination by NMR spectroscopy is time consuming and expensive. Residual Dipolar Couplings (RDCs) have become an alternate approach for structure calculation by NMR spectroscopy. In previous works, the software package REDCRAFT has been presented as a means of harnessing the information containing in RDCs for structure calculation of proteins. However, to meet its full potential, several improvements to REDCRAFT must be made., Results: In this work, we present improvements to REDCRAFT that include increased usability, better interoperability, and a more robust core algorithm. We have demonstrated the impact of the improved core algorithm in the successful folding of the protein 1A1Z with as high as ±4 Hz of added error. The REDCRAFT computed structure from the highly corrupted data exhibited less than 1.0 Å with respect to the X-ray structure. We have also demonstrated the interoperability of REDCRAFT in a few instances including with PDBMine to reduce the amount of required data in successful folding of proteins to unprecedented levels. Here we have demonstrated the successful folding of the protein 1D3Z (to within 2.4 Å of the X-ray structure) using only N-H RDCs from one alignment medium., Conclusions: The additional GUI features of REDCRAFT combined with the NEF compliance have significantly increased the flexibility and usability of this software package. The improvements of the core algorithm have substantially improved the robustness of REDCRAFT in utilizing less experimental data both in quality and quantity.

Background: In systems biology, it is of great interest to identify previously unreported associations between genes. Recently, biomedical literature has been considered as a valuable resource for this purpose. While classical clustering algorithms have popularly been used to investigate associations among genes, they are not tuned for the literature mining data and are also based on strong assumptions, which are often violated in this type of data. For example, these approaches often assume homogeneity and independence among observations. However, these assumptions are often violated due to both redundancies in functional descriptions and biological functions shared among genes. Latent block models can be alternatives in this case but they also often show suboptimal performances, especially when signals are weak. In addition, they do not allow to utilize valuable prior biological knowledge, such as those available in existing databases., Results: In order to address these limitations, here we propose PALMER, a constrained latent block model that allows to identify indirect relationships among genes based on the biomedical literature mining data. By automatically associating relevant Gene Ontology terms, PALMER facilitates biological interpretation of novel findings without laborious downstream analyses. PALMER also allows researchers to utilize prior biological knowledge about known gene-pathway relationships to guide identification of gene-gene associations. We evaluated PALMER with simulation studies and applications to studies of pathway-modulating genes relevant to cancer signaling pathways, while utilizing biological pathway annotations available in the KEGG database as prior knowledge., Conclusions: We showed that PALMER outperforms traditional latent block models and it provides reliable identification of novel gene-gene associations by utilizing prior biological knowledge, especially when signals are weak in the biomedical literature mining dataset. We believe that PALMER and its relevant user-friendly software will be powerful tools that can be used to improve existing pathway annotations and identify novel pathway-modulating genes.

Background: Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors and its average survival time is less than 1 year after diagnosis., Results: Firstly, this study aims to develop the novel survival analysis algorithms to explore the key genes and proteins related to GBM. Then, we explore the significant correlation between AEBP1 upregulation and increased EGFR expression in primary glioma, and employ a glioma cell line LN229 to identify relevant proteins and molecular pathways through protein network analysis. Finally, we identify that AEBP1 exerts its tumor-promoting effects by mainly activating mTOR pathway in Glioma., Conclusions: We summarize the whole process of the experiment and discuss how to expand our experiment in the future.

Background: About 90% of patients who have diabetes suffer from Type 2 DM (T2DM). Many studies suggest using the significant role of lncRNAs to improve the diagnosis of T2DM. Machine learning and Data Mining techniques are tools that can improve the analysis and interpretation or extraction of knowledge from the data. These techniques may enhance the prognosis and diagnosis associated with reducing diseases such as T2DM. We applied four classification models, including K-nearest neighbor (KNN), support vector machine (SVM), logistic regression, and artificial neural networks (ANN) for diagnosing T2DM, and we compared the diagnostic power of these algorithms with each other. We performed the algorithms on six LncRNA variables (LINC00523, LINC00995, HCG27_201, TPT1-AS1, LY86-AS1, DKFZP) and demographic data., Results: To select the best performance, we considered the AUC, sensitivity, specificity, plotted the ROC curve, and showed the average curve and range. The mean AUC for the KNN algorithm was 91% with 0.09 standard deviation (SD); the mean sensitivity and specificity were 96 and 85%, respectively. After applying the SVM algorithm, the mean AUC obtained 95% after stratified 10-fold cross-validation, and the SD obtained 0.05. The mean sensitivity and specificity were 95 and 86%, respectively. The mean AUC for ANN and the SD were 93% and 0.03, also the mean sensitivity and specificity were 78 and 85%. At last, for the logistic regression algorithm, our results showed 95% of mean AUC, and the SD of 0.05, the mean sensitivity and specificity were 92 and 85%, respectively. According to the ROCs, the Logistic Regression and SVM had a better area under the curve compared to the others., Conclusion: We aimed to find the best data mining approach for the prediction of T2DM using six lncRNA expression. According to the finding, the maximum AUC dedicated to SVM and logistic regression, among others, KNN and ANN also had the high mean AUC and small standard deviations of AUC scores among the approaches, KNN had the highest mean sensitivity and the highest specificity belonged to SVM. This study's result could improve our knowledge about the early detection and diagnosis of T2DM using the lncRNAs as biomarkers.

Background: Identifying different types of cancer based on gene expression data has become hotspot in bioinformatics research. Clustering cancer gene expression data from multiple cancers to their own class is a significance solution. However, the characteristics of high-dimensional and small samples of gene expression data and the noise of the data make data mining and research difficult. Although there are many effective and feasible methods to deal with this problem, the possibility remains that these methods are flawed., Results: In this paper, we propose the graph regularized low-rank representation under symmetric and sparse constraints (sgLRR) method in which we introduce graph regularization based on manifold learning and symmetric sparse constraints into the traditional low-rank representation (LRR). For the sgLRR method, by means of symmetric constraint and sparse constraint, the effect of raw data noise on low-rank representation is alleviated. Further, sgLRR method preserves the important intrinsic local geometrical structures of the raw data by introducing graph regularization. We apply this method to cluster multi-cancer samples based on gene expression data, which improves the clustering quality. First, the gene expression data are decomposed by sgLRR method. And, a lowest rank representation matrix is obtained, which is symmetric and sparse. Then, an affinity matrix is constructed to perform the multi-cancer sample clustering by using a spectral clustering algorithm, i.e., normalized cuts (Ncuts). Finally, the multi-cancer samples clustering is completed., Conclusions: A series of comparative experiments demonstrate that the sgLRR method based on low rank representation has a great advantage and remarkable performance in the clustering of multi-cancer samples.

Background: Predicting disease-related genes is helpful for understanding the disease pathology and the molecular mechanisms during the disease progression. However, traditional methods are not suitable for screening genes related to the disease development, because there are some samples with weak label information in the disease dataset and a small number of genes are known disease-related genes., Results: We designed a disease-related gene mining method based on the weakly supervised learning model in this paper. The method is separated into two steps. Firstly, the differentially expressed genes are screened based on the weakly supervised learning model. In the model, the strong and weak label information at different stages of the disease progression is fully utilized. The obtained differentially expressed gene set is stable and complete after the algorithm converges. Then, we screen disease-related genes in the obtained differentially expressed gene set using transductive support vector machine based on the difference kernel function. The difference kernel function can map the input space of the original Huntington's disease gene expression dataset to the difference space. The relation between the two genes can be evaluated more accurately in the difference space and the known disease-related gene information can be used effectively., Conclusions: The experimental results show that the disease-related gene mining method based on the weakly supervised learning model can effectively improve the precision of the disease-related gene prediction compared with other excellent methods.

Background: Mining epistatic loci which affects specific phenotypic traits is an important research issue in the field of biology. Bayesian network (BN) is a graphical model which can express the relationship between genetic loci and phenotype. Until now, it has been widely used into epistasis mining in many research work. However, this method has two disadvantages: low learning efficiency and easy to fall into local optimum. Genetic algorithm has the excellence of rapid global search and avoiding falling into local optimum. It is scalable and easy to integrate with other algorithms. This work proposes an epistasis mining approach based on genetic tabu algorithm and Bayesian network (Epi-GTBN). It uses genetic algorithm into the heuristic search strategy of Bayesian network. The individual structure can be evolved through the genetic operations of selection, crossover and mutation. It can help to find the optimal network structure, and then further to mine the epistasis loci effectively. In order to enhance the diversity of the population and obtain a more effective global optimal solution, we use the tabu search strategy into the operations of crossover and mutation in genetic algorithm. It can help to accelerate the convergence of the algorithm., Results: We compared Epi-GTBN with other recent algorithms using both simulated and real datasets. The experimental results demonstrate that our method has much better epistasis detection accuracy in the case of not affecting the efficiency for different datasets., Conclusions: The presented methodology (Epi-GTBN) is an effective method for epistasis detection, and it can be seen as an interesting addition to the arsenal used in complex traits analyses.

Background: Advances in medical technology have allowed for customized prognosis, diagnosis, and treatment regimens that utilize multiple heterogeneous data sources. Multiple kernel learning (MKL) is well suited for the integration of multiple high throughput data sources. MKL remains to be under-utilized by genomic researchers partly due to the lack of unified guidelines for its use, and benchmark genomic datasets., Results: We provide three implementations of MKL in R. These methods are applied to simulated data to illustrate that MKL can select appropriate models. We also apply MKL to combine clinical information with miRNA gene expression data of ovarian cancer study into a single analysis. Lastly, we show that MKL can identify gene sets that are known to play a role in the prognostic prediction of 15 cancer types using gene expression data from The Cancer Genome Atlas, as well as, identify new gene sets for the future research., Conclusion: Multiple kernel learning coupled with modern optimization techniques provides a promising learning tool for building predictive models based on multi-source genomic data. MKL also provides an automated scheme for kernel prioritization and parameter tuning. The methods used in the paper are implemented as an R package called RMKL package, which is freely available for download through CRAN at https://CRAN.R-project.org/package=RMKL .

Background: Computational drug repositioning, which aims to find new applications for existing drugs, is gaining more attention from the pharmaceutical companies due to its low attrition rate, reduced cost, and shorter timelines for novel drug discovery. Nowadays, a growing number of researchers are utilizing the concept of recommendation systems to answer the question of drug repositioning. Nevertheless, there still lie some challenges to be addressed: 1) Learning ability deficiencies; the adopted model cannot learn a higher level of drug-disease associations from the data. 2) Data sparseness limits the generalization ability of the model. 3)Model is easy to overfit if the effect of negative samples is not taken into consideration., Results: In this study, we propose a novel method for computational drug repositioning, Additional Neural Matrix Factorization (ANMF). The ANMF model makes use of drug-drug similarities and disease-disease similarities to enhance the representation information of drugs and diseases in order to overcome the matter of data sparsity. By means of a variant version of the autoencoder, we were able to uncover the hidden features of both drugs and diseases. The extracted hidden features will then participate in a collaborative filtering process by incorporating the Generalized Matrix Factorization (GMF) method, which will ultimately give birth to a model with a stronger learning ability. Finally, negative sampling techniques are employed to strengthen the training set in order to minimize the likelihood of model overfitting. The experimental results on the Gottlieb and Cdataset datasets show that the performance of the ANMF model outperforms state-of-the-art methods., Conclusions: Through performance on two real-world datasets, we believe that the proposed model will certainly play a role in answering to the major challenge in drug repositioning, which lies in predicting and choosing new therapeutic indications to prospectively test for a drug of interest.

Background: Using knowledge-based interpretation to analyze omics data can not only obtain essential information regarding various biological processes, but also reflect the current physiological status of cells and tissue. The major challenge to analyze gene expression data, with a large number of genes and small samples, is to extract disease-related information from a massive amount of redundant data and noise. Gene selection, eliminating redundant and irrelevant genes, has been a key step to address this problem., Results: The modified method was tested on four benchmark datasets with either two-class phenotypes or multiclass phenotypes, outperforming previous methods, with relatively higher accuracy, true positive rate, false positive rate and reduced runtime., Conclusions: This paper proposes an effective feature selection method, combining double RBF-kernels with weighted analysis, to extract feature genes from gene expression data, by exploring its nonlinear mapping ability.

Background: Frequent subgraphs mining is a significant problem in many practical domains. The solution of this kind of problem can particularly used in some large-scale drug molecular or biological libraries to help us find drugs or core biological structures rapidly and predict toxicity of some unknown compounds. The main challenge is its efficiency, as (i) it is computationally intensive to test for graph isomorphisms, and (ii) the graph collection to be mined and mining results can be very large. Existing solutions often require days to derive mining results from biological networks even with relative low support threshold. Also, the whole mining results always cannot be stored in single node memory., Results: In this paper, we implement a parallel acceleration tool for classical frequent subgraph mining algorithm called cmFSM. The core idea is to employ parallel techniques to parallelize extension tasks, so as to reduce computation time. On the other hand, we employ multi-node strategy to solve the problem of memory constraints. The parallel optimization of cmFSM is carried out on three different levels, including the fine-grained OpenMP parallelization on single node, multi-node multi-process parallel acceleration and CPU-MIC collaborated parallel optimization., Conclusions: Evaluation results show that cmFSM clearly outperforms the existing state-of-the-art miners even if we only hold a few parallel computing resources. It means that cmFSM provides a practical solution to frequent subgraph mining problem with huge number of mining results. Specifically, our solution is up to one order of magnitude faster than the best CPU-based approach on single node and presents a promising scalability of massive mining tasks in multi-node scenario. More source code are available at:Source Code: https://github.com/ysycloud/cmFSM .

Background: Given a set of features, researchers are often interested in partitioning objects into homogeneous clusters. In health research, cancer research in particular, high-throughput data is collected with the aim of segmenting patients into sub-populations to aid in disease diagnosis, prognosis or response to therapy. Cluster analysis, a class of unsupervised learning techniques, is often used for class discovery. Cluster analysis suffers from some limitations, including the need to select up-front the algorithm to be used as well as the number of clusters to generate, in addition, there may exist several groupings consistent with the data, making it very difficult to validate a final solution. Ensemble clustering is a technique used to mitigate these limitations and facilitate the generalization and reproducibility of findings in new cohorts of patients., Results: We introduce diceR (diverse cluster ensemble in R), a software package available on CRAN: https://CRAN.R-project.org/package=diceR CONCLUSIONS: diceR is designed to provide a set of tools to guide researchers through a general cluster analysis process that relies on minimizing subjective decision-making. Although developed in a biological context, the tools in diceR are data-agnostic and thus can be applied in different contexts.

Background: The Experimental Factor Ontology (EFO) is an application ontology driven by experimental variables including cell lines to organize and describe the diverse experimental variables and data resided in the EMBL-EBI resources. The Cell Line Ontology (CLO) is an OBO community-based ontology that contains information of immortalized cell lines and relevant experimental components. EFO integrates and extends ontologies from the bio-ontology community to drive a number of practical applications. It is desirable that the community shares design patterns and therefore that EFO reuses the cell line representation from the Cell Line Ontology (CLO). There are, however, challenges to be addressed when developing a common ontology design pattern for representing cell lines in both EFO and CLO., Results: In this study, we developed a strategy to compare and map cell line terms between EFO and CLO. We examined Cellosaurus resources for EFO-CLO cross-references. Text labels of cell lines from both ontologies were verified by biological information axiomatized in each source. The study resulted in the identification 873 EFO-CLO aligned and 344 EFO unique immortalized permanent cell lines. All of these cell lines were updated to CLO and the cell line related information was merged. A design pattern that integrates EFO and CLO was also developed., Conclusion: Our study compared, aligned, and synchronized the cell line information between CLO and EFO. The final updated CLO will be examined as the candidate ontology to import and replace eligible EFO cell line classes thereby supporting the interoperability in the bio-ontology domain. Our mapping pipeline illustrates the use of ontology in aiding biological data standardization and integration through the biological and semantics content of cell lines.

Background: Next-generation sequencing (NGS) technologies have provided researchers with vast possibilities in various biological and biomedical research areas. Efficient data mining strategies are in high demand for large scale comparative and evolutional studies to be performed on the large amounts of data derived from NGS projects. Topic modeling is an active research field in machine learning and has been mainly used as an analytical tool to structure large textual corpora for data mining., Methods: We report a novel procedure to analyse NGS data using topic modeling. It consists of four major procedures: NGS data retrieval, preprocessing, topic modeling, and data mining using Latent Dirichlet Allocation (LDA) topic outputs. The NGS data set of the Salmonella enterica strains were used as a case study to show the workflow of this procedure. The perplexity measurement of the topic numbers and the convergence efficiencies of Gibbs sampling were calculated and discussed for achieving the best result from the proposed procedure., Results: The output topics by LDA algorithms could be treated as features of Salmonella strains to accurately describe the genetic diversity of fliC gene in various serotypes. The results of a two-way hierarchical clustering and data matrix analysis on LDA-derived matrices successfully classified Salmonella serotypes based on the NGS data. The implementation of topic modeling in NGS data analysis procedure provides a new way to elucidate genetic information from NGS data, and identify the gene-phenotype relationships and biomarkers, especially in the era of biological and medical big data., Conclusion: The implementation of topic modeling in NGS data analysis provides a new way to elucidate genetic information from NGS data, and identify the gene-phenotype relationships and biomarkers, especially in the era of biological and medical big data.

Background: Detection of tandem duplication within coding exons, referred to as internal tandem duplication (ITD), remains challenging due to inefficiencies in alignment of ITD-containing reads to the reference genome. There is a critical need to develop efficient methods to recover these important mutational events., Results: In this paper we introduce ITD Assembler, a novel approach that rapidly evaluates all unmapped and partially mapped reads from whole exome NGS data using a De Bruijn graphs approach to select reads that harbor cycles of appropriate length, followed by assembly using overlap-layout-consensus. We tested ITD Assembler on The Cancer Genome Atlas AML dataset as a truth set. ITD Assembler identified the highest percentage of reported FLT3-ITDs when compared to other ITD detection algorithms, and discovered additional ITDs in FLT3, KIT, CEBPA, WT1 and other genes. Evidence of polymorphic ITDs in 54 genes were also found. Novel ITDs were validated by analyzing the corresponding RNA sequencing data., Conclusions: ITD Assembler is a very sensitive tool which can detect partial, large and complex tandem duplications. This study highlights the need to more effectively look for ITD's in other cancers and Mendelian diseases.

Background: Effective management of patients with diabetic foot infection is a crucial concern. A delay in prescribing appropriate antimicrobial agent can lead to amputation or life threatening complications. Thus, this electronic nose (e-nose) technique will provide a diagnostic tool that will allow for rapid and accurate identification of a pathogen., Results: This study investigates the performance of e-nose technique performing direct measurement of static headspace with algorithm and data interpretations which was validated by Headspace SPME-GC-MS, to determine the causative bacteria responsible for diabetic foot infection. The study was proposed to complement the wound swabbing method for bacterial culture and to serve as a rapid screening tool for bacteria species identification. The investigation focused on both single and poly microbial subjected to different agar media cultures. A multi-class technique was applied including statistical approaches such as Support Vector Machine (SVM), K Nearest Neighbor (KNN), Linear Discriminant Analysis (LDA) as well as neural networks called Probability Neural Network (PNN). Most of classifiers successfully identified poly and single microbial species with up to 90% accuracy., Conclusions: The results obtained from this study showed that the e-nose was able to identify and differentiate between poly and single microbial species comparable to the conventional clinical technique. It also indicates that even though poly and single bacterial species in different agar solution emit different headspace volatiles, they can still be discriminated and identified using multivariate techniques.

Background: In genomics, hierarchical clustering (HC) is a popular method for grouping similar samples based on a distance measure. HC algorithms do not actually create clusters, but compute a hierarchical representation of the data set. Usually, a fixed height on the HC tree is used, and each contiguous branch of samples below that height is considered a separate cluster. Due to the fixed-height cutting, those clusters may not unravel significant functional coherence hidden deeper in the tree. Besides that, most existing approaches do not make use of available clinical information to guide cluster extraction from the HC. Thus, the identified subgroups may be difficult to interpret in relation to that information., Results: We develop a novel framework for decomposing the HC tree into clusters by semi-supervised piecewise snipping. The framework, called guided piecewise snipping, utilizes both molecular data and clinical information to decompose the HC tree into clusters. It cuts the given HC tree at variable heights to find a partition (a set of non-overlapping clusters) which does not only represent a structure deemed to underlie the data from which HC tree is derived, but is also maximally consistent with the supplied clinical data. Moreover, the approach does not require the user to specify the number of clusters prior to the analysis. Extensive results on simulated and multiple medical data sets show that our approach consistently produces more meaningful clusters than the standard fixed-height cut and/or non-guided approaches., Conclusions: The guided piecewise snipping approach features several novelties and advantages over existing approaches. The proposed algorithm is generic, and can be combined with other algorithms that operate on detected clusters. This approach represents an advancement in several regards: (1) a piecewise tree snipping framework that efficiently extracts clusters by snipping the HC tree possibly at variable heights while preserving the HC tree structure; (2) a flexible implementation allowing a variety of data types for both building and snipping the HC tree, including patient follow-up data like survival as auxiliary information. The data sets and R code are provided as supplementary files. The proposed method is available from Bioconductor as the R-package HCsnip.

Background: There is an ever-expanding range of technologies that generate very large numbers of biomarkers for research and clinical applications. Choosing the most informative biomarkers from a high-dimensional data set, combined with identifying the most reliable and accurate classification algorithms to use with that biomarker set, can be a daunting task. Existing surveys of feature selection and classification algorithms typically focus on a single data type, such as gene expression microarrays, and rarely explore the model's performance across multiple biological data types., Results: This paper presents the results of a large scale empirical study whereby a large number of popular feature selection and classification algorithms are used to identify the tissue of origin for the NCI-60 cancer cell lines. A computational pipeline was implemented to maximize predictive accuracy of all models at all parameters on five different data types available for the NCI-60 cell lines. A validation experiment was conducted using external data in order to demonstrate robustness., Conclusions: As expected, the data type and number of biomarkers have a significant effect on the performance of the predictive models. Although no model or data type uniformly outperforms the others across the entire range of tested numbers of markers, several clear trends are visible. At low numbers of biomarkers gene and protein expression data types are able to differentiate between cancer cell lines significantly better than the other three data types, namely SNP, array comparative genome hybridization (aCGH), and microRNA data.

Background: Observation of gene expression changes implying gene regulations using a repetitive experiment in time course has become more and more important. However, there is no effective method which can handle such kind of data. For instance, in a clinical/biological progression like inflammatory response or cancer formation, a great number of differentially expressed genes at different time points could be identified through a large-scale microarray approach. For each repetitive experiment with different samples, converting the microarray datasets into transactional databases with significant singleton genes at each time point would allow sequential patterns implying gene regulations to be identified. Although traditional sequential pattern mining methods have been successfully proposed and widely used in different interesting topics, like mining customer purchasing sequences from a transactional database, to our knowledge, the methods are not suitable for such biological dataset because every transaction in the converted database may contain too many items/genes., Results: In this paper, we propose a new algorithm called CTGR-Span (Cross-Timepoint Gene Regulation Sequential pattern) to efficiently mine CTGR-SPs (Cross-Timepoint Gene Regulation Sequential Patterns) even on larger datasets where traditional algorithms are infeasible. The CTGR-Span includes several biologically designed parameters based on the characteristics of gene regulation. We perform an optimal parameter tuning process using a GO enrichment analysis to yield CTGR-SPs more meaningful biologically. The proposed method was evaluated with two publicly available human time course microarray datasets and it was shown that it outperformed the traditional methods in terms of execution efficiency. After evaluating with previous literature, the resulting patterns also strongly correlated with the experimental backgrounds of the datasets used in this study., Conclusions: We propose an efficient CTGR-Span to mine several biologically meaningful CTGR-SPs. We postulate that the biologist can benefit from our new algorithm since the patterns implying gene regulations could provide further insights into the mechanisms of novel gene regulations during a biological or clinical progression. The Java source code, program tutorial and other related materials used in this program are available at http://websystem.csie.ncku.edu.tw/CTGR-Span.rar.

Background: Huge numbers of genomes can now be sequenced rapidly with recent improvements in sequencing throughput. However, data analysis methods have not kept up, making it difficult to process the vast amounts of available sequence data. This increased processing time is especially critical in DNA sequence clustering because of the intrinsic difficulty in parallelization. Thus, there is a strong demand for a faster clustering algorithm., Results: We developed a new fast DNA sequence clustering method called LCS-HIT, based on the popular CD-HIT program. The proposed method uses a novel filtering technique based on the longest common subsequence to identify similar sequence pairs. This filtering technique makes the LCS-HIT considerably faster than CD-HIT, without loss of sensitivity. For a dataset of two million DNA sequences, our method was approximately 7.1, 4.4, and 2.2 times faster than CD-HIT for 100, 150, and 400 bases, respectively., Conclusions: The LCS-HIT clustering program, using a novel filtering technique based on the longest common subsequence, is significantly faster than CD-HIT without compromising clustering accuracy. Moreover, the filtering technique itself is independent from the CD-HIT algorithm. Thus, this technique can be applied to similar clustering algorithms.

Background: We explore techniques for performing model combination between the UMass and Stanford biomedical event extraction systems. Both sub-components address event extraction as a structured prediction problem, and use dual decomposition (UMass) and parsing algorithms (Stanford) to find the best scoring event structure. Our primary focus is on stacking where the predictions from the Stanford system are used as features in the UMass system. For comparison, we look at simpler model combination techniques such as intersection and union which require only the outputs from each system and combine them directly., Results: First, we find that stacking substantially improves performance while intersection and union provide no significant benefits. Second, we investigate the graph properties of event structures and their impact on the combination of our systems. Finally, we trace the origins of events proposed by the stacked model to determine the role each system plays in different components of the output. We learn that, while stacking can propose novel event structures not seen in either base model, these events have extremely low precision. Removing these novel events improves our already state-of-the-art F1 to 56.6% on the test set of Genia (Task 1). Overall, the combined system formed via stacking ("FAUST") performed well in the BioNLP 2011 shared task. The FAUST system obtained 1st place in three out of four tasks: 1st place in Genia Task 1 (56.0% F1) and Task 2 (53.9%), 2nd place in the Epigenetics and Post-translational Modifications track (35.0%), and 1st place in the Infectious Diseases track (55.6%)., Conclusion: We present a state-of-the-art event extraction system that relies on the strengths of structured prediction and model combination through stacking. Akin to results on other tasks, stacking outperforms intersection and union and leads to very strong results. The utility of model combination hinges on complementary views of the data, and we show that our sub-systems capture different graph properties of event structures. Finally, by removing low precision novel events, we show that performance from stacking can be further improved.

Background: In recent years, biological event extraction has emerged as a key natural language processing task, aiming to address the information overload problem in accessing the molecular biology literature. The BioNLP shared task competitions have contributed to this recent interest considerably. The first competition (BioNLP'09) focused on extracting biological events from Medline abstracts from a narrow domain, while the theme of the latest competition (BioNLP-ST'11) was generalization and a wider range of text types, event types, and subject domains were considered. We view event extraction as a building block in larger discourse interpretation and propose a two-phase, linguistically-grounded, rule-based methodology. In the first phase, a general, underspecified semantic interpretation is composed from syntactic dependency relations in a bottom-up manner. The notion of embedding underpins this phase and it is informed by a trigger dictionary and argument identification rules. Coreference resolution is also performed at this step, allowing extraction of inter-sentential relations. The second phase is concerned with constraining the resulting semantic interpretation by shared task specifications. We evaluated our general methodology on core biological event extraction and speculation/negation tasks in three main tracks of BioNLP-ST'11 (GENIA, EPI, and ID)., Results: We achieved competitive results in GENIA and ID tracks, while our results in the EPI track leave room for improvement. One notable feature of our system is that its performance across abstracts and articles bodies is stable. Coreference resolution results in minor improvement in system performance. Due to our interest in discourse-level elements, such as speculation/negation and coreference, we provide a more detailed analysis of our system performance in these subtasks., Conclusions: The results demonstrate the viability of a robust, linguistically-oriented methodology, which clearly distinguishes general semantic interpretation from shared task specific aspects, for biological event extraction. Our error analysis pinpoints some shortcomings, which we plan to address in future work within our incremental system development methodology.

Background: Biological networks provide fundamental insights into the functional characterization of genes and their products, the characterization of DNA-protein interactions, the identification of regulatory mechanisms, and other biological tasks. Due to the experimental and biological complexity, their computational exploitation faces many algorithmic challenges., Results: We introduce novel weighted quasi-biclique problems to identify functional modules in biological networks when represented by bipartite graphs. In difference to previous quasi-biclique problems, we include biological interaction levels by using edge-weighted quasi-bicliques. While we prove that our problems are NP-hard, we also describe IP formulations to compute exact solutions for moderately sized networks., Conclusions: We verify the effectiveness of our IP solutions using both simulation and empirical data. The simulation shows high quasi-biclique recall rates, and the empirical data corroborate the abilities of our weighted quasi-bicliques in extracting features and recovering missing interactions from biological networks.

Background: Most computational algorithms mainly focus on detecting highly connected subgraphs in PPI networks as protein complexes but ignore their inherent organization. Furthermore, many of these algorithms are computationally expensive. However, recent analysis indicates that experimentally detected protein complexes generally contain Core/attachment structures., Methods: In this paper, a Greedy Search Method based on Core-Attachment structure (GSM-CA) is proposed. The GSM-CA method detects densely connected regions in large protein-protein interaction networks based on the edge weight and two criteria for determining core nodes and attachment nodes. The GSM-CA method improves the prediction accuracy compared to other similar module detection approaches, however it is computationally expensive. Many module detection approaches are based on the traditional hierarchical methods, which is also computationally inefficient because the hierarchical tree structure produced by these approaches cannot provide adequate information to identify whether a network belongs to a module structure or not. In order to speed up the computational process, the Greedy Search Method based on Fast Clustering (GSM-FC) is proposed in this work. The edge weight based GSM-FC method uses a greedy procedure to traverse all edges just once to separate the network into the suitable set of modules., Results: The proposed methods are applied to the protein interaction network of S. cerevisiae. Experimental results indicate that many significant functional modules are detected, most of which match the known complexes. Results also demonstrate that the GSM-FC algorithm is faster and more accurate as compared to other competing algorithms., Conclusions: Based on the new edge weight definition, the proposed algorithm takes advantages of the greedy search procedure to separate the network into the suitable set of modules. Experimental analysis shows that the identified modules are statistically significant. The algorithm can reduce the computational time significantly while keeping high prediction accuracy.

Background: High-throughput technologies such as DNA, RNA, protein, antibody and peptide microarrays are often used to examine differences across drug treatments, diseases, transgenic animals, and others. Typically one trains a classification system by gathering large amounts of probe-level data, selecting informative features, and classifies test samples using a small number of features. As new microarrays are invented, classification systems that worked well for other array types may not be ideal. Expression microarrays, arguably one of the most prevalent array types, have been used for years to help develop classification algorithms. Many biological assumptions are built into classifiers that were designed for these types of data. One of the more problematic is the assumption of independence, both at the probe level and again at the biological level. Probes for RNA transcripts are designed to bind single transcripts. At the biological level, many genes have dependencies across transcriptional pathways where co-regulation of transcriptional units may make many genes appear as being completely dependent. Thus, algorithms that perform well for gene expression data may not be suitable when other technologies with different binding characteristics exist. The immunosignaturing microarray is based on complex mixtures of antibodies binding to arrays of random sequence peptides. It relies on many-to-many binding of antibodies to the random sequence peptides. Each peptide can bind multiple antibodies and each antibody can bind multiple peptides. This technology has been shown to be highly reproducible and appears promising for diagnosing a variety of disease states. However, it is not clear what is the optimal classification algorithm for analyzing this new type of data., Results: We characterized several classification algorithms to analyze immunosignaturing data. We selected several datasets that range from easy to difficult to classify, from simple monoclonal binding to complex binding patterns in asthma patients. We then classified the biological samples using 17 different classification algorithms. Using a wide variety of assessment criteria, we found 'Naïve Bayes' far more useful than other widely used methods due to its simplicity, robustness, speed and accuracy., Conclusions: 'Naïve Bayes' algorithm appears to accommodate the complex patterns hidden within multilayered immunosignaturing microarray data due to its fundamental mathematical properties.

Background: The growth of the biomedical information requires most information retrieval systems to provide short and specific answers in response to complex user queries. Semantic information in the form of free text that is structured in a way makes it straightforward for humans to read but more difficult for computers to interpret automatically and search efficiently. One of the reasons is that most traditional information retrieval models assume terms are conditionally independent given a document/passage. Therefore, we are motivated to consider term associations within different contexts to help the models understand semantic information and use it for improving biomedical information retrieval performance., Results: We propose a term association approach to discover term associations among the keywords from a query. The experiments are conducted on the TREC 2004-2007 Genomics data sets and the TREC 2004 HARD data set. The proposed approach is promising and achieves superiority over the baselines and the GSP results. The parameter settings and different indices are investigated that the sentence-based index produces the best results in terms of the document-level, the word-based index for the best results in terms of the passage-level and the paragraph-based index for the best results in terms of the passage2-level. Furthermore, the best term association results always come from the best baseline. The tuning number k in the proposed recursive re-ranking algorithm is discussed and locally optimized to be 10., Conclusions: First, modelling term association for improving biomedical information retrieval using factor analysis, is one of the major contributions in our work. Second, the experiments confirm that term association considering co-occurrence and dependency among the keywords can produce better results than the baselines treating the keywords independently. Third, the baselines are re-ranked according to the importance and reliance of latent factors behind term associations. These latent factors are decided by the proposed model and their term appearances in the first round retrieved passages.

Background: Nowadays, it is possible to collect expression levels of a set of genes from a set of biological samples during a series of time points. Such data have three dimensions: gene-sample-time (GST). Thus they are called 3D microarray gene expression data. To take advantage of the 3D data collected, and to fully understand the biological knowledge hidden in the GST data, novel subspace clustering algorithms have to be developed to effectively address the biological problem in the corresponding space., Results: We developed a subspace clustering algorithm called Order Preserving Triclustering (OPTricluster), for 3D short time-series data mining. OPTricluster is able to identify 3D clusters with coherent evolution from a given 3D dataset using a combinatorial approach on the sample dimension, and the order preserving (OP) concept on the time dimension. The fusion of the two methodologies allows one to study similarities and differences between samples in terms of their temporal expression profile. OPTricluster has been successfully applied to four case studies: immune response in mice infected by malaria (Plasmodium chabaudi), systemic acquired resistance in Arabidopsis thaliana, similarities and differences between inner and outer cotyledon in Brassica napus during seed development, and to Brassica napus whole seed development. These studies showed that OPTricluster is robust to noise and is able to detect the similarities and differences between biological samples., Conclusions: Our analysis showed that OPTricluster generally outperforms other well known clustering algorithms such as the TRICLUSTER, gTRICLUSTER and K-means; it is robust to noise and can effectively mine the biological knowledge hidden in the 3D short time-series gene expression data.

Background: Determining usefulness of biomedical text mining systems requires realistic task definition and data selection criteria without artificial constraints, measuring performance aspects that go beyond traditional metrics. The BioCreative III Protein-Protein Interaction (PPI) tasks were motivated by such considerations, trying to address aspects including how the end user would oversee the generated output, for instance by providing ranked results, textual evidence for human interpretation or measuring time savings by using automated systems. Detecting articles describing complex biological events like PPIs was addressed in the Article Classification Task (ACT), where participants were asked to implement tools for detecting PPI-describing abstracts. Therefore the BCIII-ACT corpus was provided, which includes a training, development and test set of over 12,000 PPI relevant and non-relevant PubMed abstracts labeled manually by domain experts and recording also the human classification times. The Interaction Method Task (IMT) went beyond abstracts and required mining for associations between more than 3,500 full text articles and interaction detection method ontology concepts that had been applied to detect the PPIs reported in them., Results: A total of 11 teams participated in at least one of the two PPI tasks (10 in ACT and 8 in the IMT) and a total of 62 persons were involved either as participants or in preparing data sets/evaluating these tasks. Per task, each team was allowed to submit five runs offline and another five online via the BioCreative Meta-Server. From the 52 runs submitted for the ACT, the highest Matthew's Correlation Coefficient (MCC) score measured was 0.55 at an accuracy of 89% and the best AUC iP/R was 68%. Most ACT teams explored machine learning methods, some of them also used lexical resources like MeSH terms, PSI-MI concepts or particular lists of verbs and nouns, some integrated NER approaches. For the IMT, a total of 42 runs were evaluated by comparing systems against manually generated annotations done by curators from the BioGRID and MINT databases. The highest AUC iP/R achieved by any run was 53%, the best MCC score 0.55. In case of competitive systems with an acceptable recall (above 35%) the macro-averaged precision ranged between 50% and 80%, with a maximum F-Score of 55%., Conclusions: The results of the ACT task of BioCreative III indicate that classification of large unbalanced article collections reflecting the real class imbalance is still challenging. Nevertheless, text-mining tools that report ranked lists of relevant articles for manual selection can potentially reduce the time needed to identify half of the relevant articles to less than 1/4 of the time when compared to unranked results. Detecting associations between full text articles and interaction detection method PSI-MI terms (IMT) is more difficult than might be anticipated. This is due to the variability of method term mentions, errors resulting from pre-processing of articles provided as PDF files, and the heterogeneity and different granularity of method term concepts encountered in the ontology. However, combining the sophisticated techniques developed by the participants with supporting evidence strings derived from the articles for human interpretation could result in practical modules for biological annotation workflows.

Background: Word sense disambiguation (WSD) attempts to solve lexical ambiguities by identifying the correct meaning of a word based on its context. WSD has been demonstrated to be an important step in knowledge-based approaches to automatic summarization. However, the correlation between the accuracy of the WSD methods and the summarization performance has never been studied., Results: We present three existing knowledge-based WSD approaches and a graph-based summarizer. Both the WSD approaches and the summarizer employ the Unified Medical Language System (UMLS) Metathesaurus as the knowledge source. We first evaluate WSD directly, by comparing the prediction of the WSD methods to two reference sets: the NLM WSD dataset and the MSH WSD collection. We next apply the different WSD methods as part of the summarizer, to map documents onto concepts in the UMLS Metathesaurus, and evaluate the summaries that are generated. The results obtained by the different methods in both evaluations are studied and compared., Conclusions: It has been found that the use of WSD techniques has a positive impact on the results of our graph-based summarizer, and that, when both the WSD and summarization tasks are assessed over large and homogeneous evaluation collections, there exists a correlation between the overall results of the WSD and summarization tasks. Furthermore, the best WSD algorithm in the first task tends to be also the best one in the second. However, we also found that the improvement achieved by the summarizer is not directly correlated with the WSD performance. The most likely reason is that the errors in disambiguation are not equally important but depend on the relative salience of the different concepts in the document to be summarized.

Background: Experimentally verified protein-protein interactions (PPIs) cannot be easily retrieved by researchers unless they are stored in PPI databases. The curation of such databases can be facilitated by employing text-mining systems to identify genes which play the interactor role in PPIs and to map these genes to unique database identifiers (interactor normalization task or INT) and then to return a list of interaction pairs for each article (interaction pair task or IPT). These two tasks are evaluated in terms of the area under curve of the interpolated precision/recall (AUC iP/R) score because the order of identifiers in the output list is important for ease of curation., Results: Our INT system developed for the BioCreAtIvE II.5 INT challenge achieved a promising AUC iP/R of 43.5% by using a support vector machine (SVM)-based ranking procedure. Using our new re-ranking algorithm, we have been able to improve system performance (AUC iP/R) by 1.84%. Our experimental results also show that with the re-ranked INT results, our unsupervised IPT system can achieve a competitive AUC iP/R of 23.86%, which outperforms the best BC II.5 INT system by 1.64%. Compared to using only SVM ranked INT results, using re-ranked INT results boosts AUC iP/R by 7.84%. Statistical significance t-test results show that our INT/IPT system with re-ranking outperforms that without re-ranking by a statistically significant difference., Conclusions: In this paper, we present a new re-ranking algorithm that considers co-occurrence among identifiers in an article to improve INT and IPT ranking results. Combining the re-ranked INT results with an unsupervised approach to find associations among interactors, the proposed method can boost the IPT performance. We also implement score computation using dynamic programming, which is faster and more efficient than traditional approaches.

Background: Phosphorylation motifs represent common patterns around the phosphorylation site. The discovery of such kinds of motifs reveals the underlying regulation mechanism and facilitates the prediction of unknown phosphorylation event. To date, people have gathered large amounts of phosphorylation data, making it possible to perform substrate-driven motif discovery using data mining techniques., Results: We describe an algorithm called Motif-All that is able to efficiently identify all statistically significant motifs. The proposed method explores a support constraint to reduce search space and avoid generating random artifacts. As the number of phosphorylated peptides are far less than that of unphosphorylated ones, we divide the mining process into two stages: The first step generates candidates from the set of phosphorylated sequences using only support constraint and the second step tests the statistical significance of each candidate using the odds ratio derived from the whole data set. Experimental results on real data show that Motif-All outperforms current algorithms in terms of both effectiveness and efficiency., Conclusions: Motif-All is a useful tool for discovering statistically significant phosphorylation motifs. Source codes and data sets are available at: http://bioinformatics.ust.hk/MotifAll.rar.

Background: The amount of available biological information is rapidly increasing and the focus of biological research has moved from single components to networks and even larger projects aiming at the analysis, modelling and simulation of biological networks as well as large scale comparison of cellular properties. It is therefore essential that biological knowledge is easily accessible. However, most information is contained in the written literature in an unstructured way, so that methods for the systematic extraction of knowledge directly from the primary literature have to be deployed., Description: Here we present a text mining algorithm for the extraction of kinetic information such as K(M), K(i), k(cat) etc. as well as associated information such as enzyme names, EC numbers, ligands, organisms, localisations, pH and temperatures. Using this rule- and dictionary-based approach, it was possible to extract 514,394 kinetic parameters of 13 categories (K(M), K(i), k(cat), k(cat)/K(M), V(max), IC(50), S(0.5), K(d), K(a), t(1/2), pI, n(H), specific activity, V(max)/K(M)) from about 17 million PubMed abstracts and combine them with other data in the abstract. A manual verification of approx. 1,000 randomly chosen results yielded a recall between 51% and 84% and a precision ranging from 55% to 96%, depending of the category searched.The results were stored in a database and are available as "KID the KInetic Database" via the internet., Conclusions: The presented algorithm delivers a considerable amount of information and therefore may aid to accelerate the research and the automated analysis required for today's systems biology approaches. The database obtained by analysing PubMed abstracts may be a valuable help in the field of chemical and biological kinetics. It is completely based upon text mining and therefore complements manually curated databases. The database is available at http://kid.tu-bs.de. The source code of the algorithm is provided under the GNU General Public Licence and available on request from the author.

Background: Computational identification of blood-secretory proteins, especially proteins with differentially expressed genes in diseased tissues, can provide highly useful information in linking transcriptomic data to proteomic studies for targeted disease biomarker discovery in serum., Results: A new algorithm for prediction of blood-secretory proteins is presented using an information-retrieval technique, called manifold ranking. On a dataset containing 305 known blood-secretory human proteins and a large number of other proteins that are either not blood-secretory or unknown, the new method performs better than the previous published method, measured in terms of the area under the recall-precision curve (AUC). A key advantage of the presented method is that it does not explicitly require a negative training set, which could often be noisy or difficult to derive for most biological problems, hence making our method more applicable than classification-based data mining methods in general biological studies., Conclusion: We believe that our program will prove to be very useful to biomedical researchers who are interested in finding serum markers, especially when they have candidate proteins derived through transcriptomic or proteomic analyses of diseased tissues. A computer program is developed for prediction of blood-secretory proteins based on manifold ranking, which is accessible at our website http://csbl.bmb.uga.edu/publications/materials/qiliu/blood_secretory_protein.html.

Background: Gene co-expression networks are widely studied in the biomedical field, with algorithms such as WGCNA and lmQCM having been developed to detect co-expressed modules. However, these algorithms have limitations such as insufficient granularity and unbalanced module size, which prevent full acquisition of knowledge from data mining. In addition, it is difficult to incorporate prior knowledge in current co-expression module detection algorithms. Results: In this paper, we propose a novel module detection algorithm based on topology potential and spectral clustering algorithm to detect co-expressed modules in gene co-expression networks. By testing on TCGA data, our novel method can provide more complete coverage of genes, more balanced module size and finer granularity than current methods in detecting modules with significant overall survival difference. In addition, the proposed algorithm can identify modules by incorporating prior knowledge. Conclusion: In summary, we developed a method to obtain as much as possible information from networks with increased input coverage and the ability to detect more size-balanced and granular modules. In addition, our method can integrate data from different sources. Our proposed method performs better than current methods with complete coverage of input genes and finer granularity. Moreover, this method is designed not only for gene co-expression networks but can also be applied to any general fully connected weighted network. [ABSTRACT FROM AUTHOR]

BackgroundHuman disease often arises as a consequence of alterations in a set of associated genes rather than alterations to a set of unassociated individual genes. Most previous microarray-based meta-analyses identified disease-associated genes or biomarkers independent of genetic interactions. Therefore, in this study, we present the first meta-analysis method capable of taking gene combination effects into account to efficiently identify associated biomarkers (ABs) across different microarray platforms.ResultsWe propose a new meta-analysis approach called MiningABs to mine ABs across different array-based datasets. The similarity between paired probe sequences is quantified as a bridge to connect these datasets together. The ABs can be subsequently identified from an "improved" common logit model (c-LM) by combining several sibling-like LMs in a heuristic genetic algorithm selection process. Our approach is evaluated with two sets of gene expression datasets: i) 4 esophageal squamous cell carcinoma and ii) 3 hepatocellular carcinoma datasets. Based on an unbiased reciprocal test, we demonstrate that each gene in a group of ABs is required to maintain high cancer sample classification accuracy, and we observe that ABs are not limited to genes common to all platforms. Investigating the ABs using Gene Ontology (GO) enrichment, literature survey, and network analyses indicated that our ABs are not only strongly related to cancer development but also highly connected in a diverse network of biological interactions.ConclusionsThe proposed meta-analysis method called MiningABs is able to efficiently identify ABs from different independently performed array-based datasets, and we show its validity in cancer biology via GO enrichment, literature survey and network analyses. We postulate that the ABs may facilitate novel target and drug discovery, leading to improved clinical treatment. Java source code, tutorial, example and related materials are available at "http://sourceforge.net/projects/miningabs/".

Background: Drug repurposing aims to detect the new therapeutic benefits of the existing drugs and reduce the spent time and cost of the drug development projects. The synthetic repurposing of drugs may prove to be more useful than the single repurposing in terms of reducing toxicity and enhancing efficacy. However, the researchers have not given it serious consideration. To address the issue, a novel datamining method is introduced and applied to repositioning of drugs for hypertension (HT) which is a serious medical condition and needs some improved treatment plans to help treat it. Results: A novel two-step data mining method, which is based on the If-Then association rules as well as a novel discrete optimization algorithm, was introduced and applied to the synthetic repurposing of drugs for HT. The required data were also extracted from DrugBank, KEGG, and DrugR+ databases. The findings indicated that based on the different statistical criteria, the proposed method outperformed the other state-of-the-art approaches. In contrast to the previously proposed methods which had failed to discover a list on some datasets, our method could find a combination list for all of them. Conclusion: Since the proposed synthetic method uses medications in small dosages, it might revive some failed drug development projects and put forward a suitable plan for treating different diseases such as COVID-19 and HT. It is also worth noting that applying efficient computational methods helps to produce better results. [ABSTRACT FROM AUTHOR]

Background: Manual extraction of information from electronic pathology (epath) reports to populate the Surveillance, Epidemiology, and End Result (SEER) database is labor intensive. Systematizing the data extraction automatically using machine-learning (ML) and natural language processing (NLP) is desirable to reduce the human labor required to populate the SEER database and to improve the timeliness of the data. This enables scaling up registry efficiency and collection of new data elements. To ensure the integrity, quality, and continuity of the SEER data, the misclassification error of ML and NPL algorithms needs to be negligible. Current algorithms fail to achieve the precision of human experts who can bring additional information in their assessments. Differences in registry format and the desire to develop a common information extraction platform further complicate the ML/NLP tasks. The purpose of our study is to develop triage rules to partially automate registry workflow to improve the precision of the auto-extracted information. Results: This paper presents a mathematical framework to improve the precision of a classifier beyond that of the Bayes classifier by selectively classifying item that are most likely to be correct. This results in a triage rule that only classifies a subset of the item. We characterize the optimal triage rule and demonstrate its usefulness in the problem of classifying cancer site from electronic pathology reports to achieve a desired precision. Conclusions: From the mathematical formalism, we propose a heuristic estimate for triage rule based on post-processing the soft-max output from standard machine learning algorithms. We show, in test cases, that the triage rule significantly improve the classification accuracy. [ABSTRACT FROM AUTHOR]