Diverse Biological Information Research Articles

Precision Drug Repurposing: A Deep Learning Toolkit for Identifying 34 Hyperpigmentation-Associated Genes and Optimizing Treatment Selection.

Hyperpigmentation is a skin disorder characterized by a localized darkening of the skin due to increased melanin production. When patients fail first line topical treatments, secondary treatments such as chemical peels and lasers are offered. However, these interventions are not devoid of risks and are associated with postinflammatory hyperpigmentation. In the quest for novel therapeutic potentials, this study aims to investigate computational methods in the identification of new targeted therapies in the treatment of hyperpigmentation. We used a comprehensive approach, which integrated text mining, interpreting gene lists through enrichment analysis and integration of diverse biological information (GeneCodis), protein-protein association networks and functional enrichment analyses (STRING), and plug-in network centrality parameters (Cytoscape) to pinpoint genes closely associated with hyperpigmentation. Subsequently, analysis of drug-gene interactions to identify potential drugs (Cortellis) was utilized to select drugs targeting these identified genes. Lastly, we used Deep Learning Based Drug Repurposing Toolkit (DeepPurpose) to conduct drug-target interaction predictions to ultimately identify candidate drugs with the most promising binding affinities. Thirty-four hyperpigmentation-related genes were identified by text mining. Eight key genes were highlighted by utilizing GeneCodis, STRING, Cytoscape, gene enrichment, and protein-protein interaction analysis. Thirty-five drugs targeting hyperpigmentation-associated genes were identified by Cortellis, and 29 drugs, including 16 M2PK1 inhibitors, 11 KRAS inhibitors, and 2 BRAF inhibitors were recommended by DeepPurpose. The study highlights the promise of advanced computational methodology for identifying potential treatments for hyperpigmentation.

ACDMBI: A deep learning model based on community division and multi-source biological information fusion predicts essential proteins

Accurately identifying essential proteins is vital for drug research and disease diagnosis. Traditional centrality methods and machine learning approaches often face challenges in accurately discerning essential proteins, primarily relying on information derived from protein-protein interaction (PPI) networks. Despite attempts by some researchers to integrate biological data and PPI networks for predicting essential proteins, designing effective integration methods remains a challenge. In response to these challenges, this paper presents the ACDMBI model, specifically designed to overcome the aforementioned issues. ACDMBI is comprised of two key modules: feature extraction and classification. In terms of capturing relevant information, we draw insights from three distinct data sources. Initially, structural features of proteins are extracted from the PPI network through community division. Subsequently, these features are further optimized using Graph Convolutional Networks (GCN) and Graph Attention Networks (GAT). Moving forward, protein features are extracted from gene expression data utilizing Bidirectional Long Short-Term Memory networks (BiLSTM) and a multi-head self-attention mechanism. Finally, protein features are derived by mapping subcellular localization data to a one-dimensional vector and processing it through fully connected layers. In the classification phase, we integrate features extracted from three different data sources, crafting a multi-layer deep neural network (DNN) for protein classification prediction. Experimental results on brewing yeast data showcase the ACDMBI model’s superior performance, with AUC reaching 0.9533 and AUPR reaching 0.9153. Ablation experiments further reveal that the effective integration of features from diverse biological information significantly boosts the model’s performance.

Exploring potential circRNA biomarkers for cancers based on double-line heterogeneous graph representation learning

BackgroundCompared with the time-consuming and labor-intensive for biological validation in vitro or in vivo, the computational models can provide high-quality and purposeful candidates in an instant. Existing computational models face limitations in effectively utilizing sparse local structural information for accurate predictions in circRNA-disease associations. This study addresses this challenge with a proposed method, CDA-DGRL (Prediction of CircRNA-Disease Association based on Double-line Graph Representation Learning), which employs a deep learning framework leveraging graph networks and a dual-line representation model integrating graph node features.MethodCDA-DGRL comprises several key steps: initially, the integration of diverse biological information to compute integrated similarities among circRNAs and diseases, leading to the construction of a heterogeneous network specific to circRNA-disease associations. Subsequently, circRNA and disease node features are derived using sparse autoencoders. Thirdly, a graph convolutional neural network is employed to capture the local graph network structure by inputting the circRNA-disease heterogeneous network alongside node features. Fourthly, the utilization of node2vec facilitates depth-first sampling of the circRNA-disease heterogeneous network to grasp the global graph network structure, addressing issues associated with sparse raw data. Finally, the fusion of local and global graph network structures is inputted into an extra trees classifier to identify potential circRNA-disease associations.ResultsThe results, obtained through a rigorous five-fold cross-validation on the circR2Disease dataset, demonstrate the superiority of CDA-DGRL with an AUC value of 0.9866 and an AUPR value of 0.9897 compared to existing state-of-the-art models. Notably, the hyper-random tree classifier employed in this model outperforms other machine learning classifiers.ConclusionThus, CDA-DGRL stands as a promising methodology for reliably identifying circRNA-disease associations, offering potential avenues to alleviate the necessity for extensive traditional biological experiments. The source code and data for this study are available at https://github.com/zywait/CDA-DGRL.

A comprehensive review of machine learning techniques for multi-omics data integration: challenges and applications in precision oncology.

Multi-omics data play a crucial role in precision medicine, mainly to understand the diverse biological interaction between different omics. Machine learning approaches have been extensively employed in this context over the years. This review aims to comprehensively summarize and categorize these advancements, focusing on the integration of multi-omics data, which includes genomics, transcriptomics, proteomics and metabolomics, alongside clinical data. We discuss various machine learning techniques and computational methodologies used for integrating distinct omics datasets and provide valuable insights into their application. The review emphasizes both the challenges and opportunities present in multi-omics data integration, precision medicine and patient stratification, offering practical recommendations for method selection in various scenarios. Recent advances in deep learning and network-based approaches are also explored, highlighting their potential to harmonize diverse biological information layers. Additionally, we present a roadmap for the integration of multi-omics data in precision oncology, outlining the advantages, challenges and implementation difficulties. Hence this review offers a thorough overview of current literature, providing researchers with insights into machine learning techniques for patient stratification, particularly in precision oncology. Contact: anirban@klyuniv.ac.in.

Precision prognosis of colorectal cancer: a multi-tiered model integrating microsatellite instability genes and clinical parameters.

Prognostic assessment for colorectal cancer (CRC) displays substantial heterogeneity, as reliance solely on traditional TNM staging falls short of achieving precise individualized predictions. The integration of diverse biological information sources holds the potential to enhance prognostic accuracy. To establish a comprehensive multi-tiered precision prognostic evaluation system for CRC by amalgamating gene expression profiles, clinical characteristics, and tumor microsatellite instability (MSI) status in CRC patients. We integrated genomic data, clinical information, and survival follow-up data from 483 CRC patients obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. MSI-related gene modules were identified using differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Three prognostic models were constructed: MSI-Related Gene Prognostic Model (Model I), Clinical Prognostic Model (Model II), and Integrated Multi-Layered Prognostic Model (Model III) by combining clinical features. Model performance was assessed and compared using Receiver Operating Characteristic (ROC) curves, Kaplan-Meier analysis, and other methods. Six MSI-related genes were selected for constructing Model I (AUC = 0.724); Model II used two clinical features (AUC = 0.684). Compared to individual models, the integrated Model III exhibited superior performance (AUC = 0.825) and demonstrated good stability in an independent dataset (AUC = 0.767). This study successfully developed and validated a comprehensive multi-tiered precision prognostic assessment model for CRC, providing an effective tool for personalized medical management of CRC.

A hybrid deep learning framework for gene regulatory network inference from single-cell transcriptomic data

Inferring gene regulatory networks (GRNs) based on gene expression profiles is able to provide an insight into a number of cellular phenotypes from the genomic level and reveal the essential laws underlying various life phenomena. Different from the bulk expression data, single-cell transcriptomic data embody cell-to-cell variance and diverse biological information, such as tissue characteristics, transformation of cell types, etc. Inferring GRNs based on such data offers unprecedented advantages for making a profound study of cell phenotypes, revealing gene functions and exploring potential interactions. However, the high sparsity, noise and dropout events of single-cell transcriptomic data pose new challenges for regulation identification. We develop a hybrid deep learning framework for GRN inference from single-cell transcriptomic data, DGRNS, which encodes the raw data and fuses recurrent neural network and convolutional neural network (CNN) to train a model capable of distinguishing related gene pairs from unrelated gene pairs. To overcome the limitations of such datasets, it applies sliding windows to extract valuable features while preserving the direction of regulation. DGRNS is constructed as a deep learning model containing gated recurrent unit network for exploring time-dependent information and CNN for learning spatially related information. Our comprehensive and detailed comparative analysis on the dataset of mouse hematopoietic stem cells illustrates that DGRNS outperforms state-of-the-art methods. The networks inferred by DGRNS are about 16% higher than the area under the receiver operating characteristic curve of other unsupervised methods and 10% higher than the area under the precision recall curve of other supervised methods. Experiments on human datasets show the strong robustness and excellent generalization of DGRNS. By comparing the predictions with standard network, we discover a series of novel interactions which are proved to be true in some specific cell types. Importantly, DGRNS identifies a series of regulatory relationships with high confidence and functional consistency, which have not yet been experimentally confirmed and merit further research.

LPI-deepGBDT: a multiple-layer deep framework based on gradient boosting decision trees for lncRNA\u2013protein interaction identification

BackgroundLong noncoding RNAs (lncRNAs) play important roles in various biological and pathological processes. Discovery of lncRNA–protein interactions (LPIs) contributes to understand the biological functions and mechanisms of lncRNAs. Although wet experiments find a few interactions between lncRNAs and proteins, experimental techniques are costly and time-consuming. Therefore, computational methods are increasingly exploited to uncover the possible associations. However, existing computational methods have several limitations. First, majority of them were measured based on one simple dataset, which may result in the prediction bias. Second, few of them are applied to identify relevant data for new lncRNAs (or proteins). Finally, they failed to utilize diverse biological information of lncRNAs and proteins.ResultsUnder the feed-forward deep architecture based on gradient boosting decision trees (LPI-deepGBDT), this work focuses on classify unobserved LPIs. First, three human LPI datasets and two plant LPI datasets are arranged. Second, the biological features of lncRNAs and proteins are extracted by Pyfeat and BioProt, respectively. Thirdly, the features are dimensionally reduced and concatenated as a vector to represent an lncRNA–protein pair. Finally, a deep architecture composed of forward mappings and inverse mappings is developed to predict underlying linkages between lncRNAs and proteins. LPI-deepGBDT is compared with five classical LPI prediction models (LPI-BLS, LPI-CatBoost, PLIPCOM, LPI-SKF, and LPI-HNM) under three cross validations on lncRNAs, proteins, lncRNA–protein pairs, respectively. It obtains the best average AUC and AUPR values under the majority of situations, significantly outperforming other five LPI identification methods. That is, AUCs computed by LPI-deepGBDT are 0.8321, 0.6815, and 0.9073, respectively and AUPRs are 0.8095, 0.6771, and 0.8849, respectively. The results demonstrate the powerful classification ability of LPI-deepGBDT. Case study analyses show that there may be interactions between GAS5 and Q15717, RAB30-AS1 and O00425, and LINC-01572 and P35637.ConclusionsIntegrating ensemble learning and hierarchical distributed representations and building a multiple-layered deep architecture, this work improves LPI prediction performance as well as effectively probes interaction data for new lncRNAs/proteins.

Application of Magnetic Resonance Imaging in the Evaluation of Nutritional Status: A Literature Review with Focus on Dialysis Patients.

Magnetic resonance imaging (MRI) is indispensable in clinical medicine for the morphological and tomographic evaluation of many parenchymal organs. With varied imaging methods, diverse biological information, such as the perfusion volume and measurements of metabolic products, can be obtained. In addition to conventional MRI for morphological assessment, diffusion-weighted MRI/diffusion tensor imaging is used to evaluate white matter structures in the brain; arterial spin labeling is used for cerebral blood flow evaluation; magnetic resonance elastography for fatty liver and cirrhosis evaluation; magnetic resonance spectroscopy for evaluation of metabolites in specific regions of the brain; and blood oxygenation level-dependent imaging for neurological exploration of eating behavior, obesity, and food perception. This range of applications will continue to expand in the future. Nutritional science is a multidisciplinary and all-inclusive field of research; therefore, there are many different applications of MRI. We present a literature review of MRI techniques that can be used to evaluate the nutritional status, particularly in patients on dialysis. We used MEDLINE as the information source, conducted a keyword search in PubMed, and found that, as a nutritional evaluation method, MRI has been used frequently to comprehensively and quantitatively evaluate muscle mass for the determination of body composition.

Predicting miRNA-Disease Association Based on Modularity Preserving Heterogeneous Network Embedding.

MicroRNAs (miRNAs) are a category of small non-coding RNAs that profoundly impact various biological processes related to human disease. Inferring the potential miRNA-disease associations benefits the study of human diseases, such as disease prevention, disease diagnosis, and drug development. In this work, we propose a novel heterogeneous network embedding-based method called MDN-NMTF (Module-based Dynamic Neighborhood Non-negative Matrix Tri-Factorization) for predicting miRNA-disease associations. MDN-NMTF constructs a heterogeneous network of disease similarity network, miRNA similarity network and a known miRNA-disease association network. After that, it learns the latent vector representation for miRNAs and diseases in the heterogeneous network. Finally, the association probability is computed by the product of the latent miRNA and disease vectors. MDN-NMTF not only successfully integrates diverse biological information of miRNAs and diseases to predict miRNA-disease associations, but also considers the module properties of miRNAs and diseases in the course of learning vector representation, which can maximally preserve the heterogeneous network structural information and the network properties. At the same time, we also extend MDN-NMTF to a new version (called MDN-NMTF2) by using modular information to improve the miRNA-disease association prediction ability. Our methods and the other four existing methods are applied to predict miRNA-disease associations in four databases. The prediction results show that our methods can improve the miRNA-disease association prediction to a high level compared with the four existing methods.

Morphology, Pandemic, and 3D

The COVID‑19 pandemic imposes the biggest restrictions on access to morphological information housed in scientific collections, compromising the progress of scientific research. Even though it is not the first event to impose restrictions on access, it is undoubtedly the most global in range. Based on this, we discuss the barriers to access information and we show 3D technology as an important tool to create routes to mitigate the effects of future restrictions. In a global sphere, there are initiatives of inter-institutional integration and international networks focused on facilitating and disseminate the implementation of digitization tools and techniques to facilitate access to diverse biological information. Notwithstanding, when we speak in 3D technology in Latin American countries, as is well noted in Brazil, this type of progress is lacking, with only isolated initiatives from some laboratories and research centers that implement 3D digitization tools, but often as experimental uses. Moreover, recent events, such as the Museu Naciona fire and the mobility restriction imposed by the COVID‑19 pandemic, reinforce the need and urgency to discuss the virtualization of natural history collections in the national territory. In this sense, we recommend photogrammetry as a more accessible and versatile technology, which could be quickly implemented in curatorial procedures. We, also, have defined criteria to establish priorities for virtualizing the collection. The virtualization of the type specimens is an inevitable and necessary task to ensure their access and expansion of their safe preservation, as established by the ICZN, and should therefore be considered as a high priority, followed by reference specimens, which are frequently accessed. Finally, to ensure Latin America advances to levels similar to those observed in other continents, it is important to establish a collaborative network of museums and other research institutions.

Contributions of regulated transcription and mRNA decay to the dynamics of gene expression.

Organisms have acquired sophisticated regulatory networks that control gene expression in response to cellular perturbations. Understanding of the mechanisms underlying the coordinated changes in gene expression in response to external and internal stimuli is a fundamental issue in biology. Recent advances in high-throughput technologies have enabled the measurement of diverse biological information, including gene expression levels, kinetics of gene expression, and interactions among gene expression regulatory molecules. By coupling these technologies with quantitative modeling, we can now uncover the biological roles and mechanisms of gene regulation at the system level. This review consists of two parts. First, we focus on the methods using uridine analogs that measure synthesis and decay rates of RNAs, which demonstrate how cells dynamically change the regulation of gene expression in response to both internal and external cues. Second, we discuss the underlying mechanisms of these changes in kinetics, including the functions of transcription factors and RNA-binding proteins. Overall, this review will help to clarify a system-level view of gene expression programs in cells. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs RNA Turnover and Surveillance > Regulation of RNA Stability RNA Methods > RNA Analyses in vitro and In Silico.

Development of Integrative Map of MicroRNA Gene Regulatory Elements.

Like many other omics types, miRNomics is the topic of increased research interest. Fast accumulation of diverse biological information generates fragmented and sometimes contradictory results. There is an urgent need for development of protocols for systematic assembling, organization and integration of accumulated genomics data. In the present study we developed a protocol for connecting microRNA (miRNA) interactions into an integrative map of miRNA regulatory elements including: upstream regulators, overlapping genomic elements and downstream targets; miRNA-target interactions (MTIs). Data integration (integromics) in miRNomics enables revealing miRNA regulatory networks, obtaining new knowledge, setting more targeted hypotheses, prioritization of candidate regions, and facilitates biomarker development.

Identifying protein complexes from heterogeneous biological data

With the increasing availability of diverse biological information for proteins, integration of heterogeneous data becomes more useful for many problems in proteomics, such as annotating protein functions, predicting novel protein-protein interactions and so on. In this paper, we present an integrative approach called InteHC (Integrative Hierarchical Clustering) to identify protein complexes from multiple data sources. Although integrating multiple sources could effectively improve the coverage of current insufficient protein interactome (the false negative issue), it could also introduce potential false-positive interactions that could hurt the performance of protein complex prediction. Our proposed InteHC method can effectively address these issues to facilitate accurate protein complex prediction and it is summarized into the following three steps. First, for each individual source/feature, InteHC computes the matrices to store the affinity scores between a protein pair that indicate their propensity to interact or co-complex relationship. Second, InteHC computes a final score matrix, which is the weighted sum of affinity scores from individual sources. In particular, the weights indicating the reliability of individual sources are learned from a supervised model (i.e., a linear ranking SVM). Finally, a hierarchical clustering algorithm is performed on the final score matrix to generate clusters as predicted protein complexes. In our experiments, we compared the results collected by our hierarchical clustering on each individual feature with those predicted by InteHC on the combined matrix. We observed that integration of heterogeneous data significantly benefits the identification of protein complexes. Moreover, a comprehensive comparison demonstrates that InteHC performs much better than 14 state-of-the-art approaches. All the experimental data and results can be downloaded from http://www.ntu.edu.sg/home/zhengjie/data/InteHC.

An Efficient Weighted Graph Strategy to Identify Differentiation Associated Genes in Embryonic Stem Cells

In the past few decades, embryonic stem cells (ESCs) were of great interest as a model system for studying early developmental processes and because of their potential therapeutic applications in regenerative medicine. However, the underlying mechanisms of ESC differentiation remain unclear, which limits our exploration of the therapeutic potential of stem cells. Fortunately, the increasing quantity and diversity of biological datasets can provide us with opportunities to explore the biological secrets. However, taking advantage of diverse biological information to facilitate the advancement of ESC research still remains a challenge. Here, we propose a scalable, efficient and flexible function prediction framework that integrates diverse biological information using a simple weighted strategy, for uncovering the genetic determinants of mouse ESC differentiation. The advantage of this approach is that it can make predictions based on dynamic information fusion, owing to the simple weighted strategy. With this approach, we identified 30 genes that had been reported to be associated with differentiation of stem cells, which we regard to be associated with differentiation or pluripotency in embryonic stem cells. We also predicted 70 genes as candidates for contributing to differentiation, which requires further confirmation. As a whole, our results showed that this strategy could be applied as a useful tool for ESC research.

Identification of ovarian cancer associated genes using an integrated approach in a Boolean framework

BackgroundCancer is a complex disease where molecular mechanism remains elusive. A systems approach is needed to integrate diverse biological information for the prognosis and therapy risk assessment using mechanistic approach to understand gene interactions in pathways and networks and functional attributes to unravel the biological behaviour of tumors.ResultsWe weighted the functional attributes based on various functional properties observed between cancerous and non-cancerous genes reported from literature. This weighing schema was then encoded in a Boolean logic framework to rank differentially expressed genes. We have identified 17 genes to be differentially expressed from a total of 11,173 genes, where ten genes are reported to be down-regulated via epigenetic inactivation and seven genes are up-regulated. Here, we report that the overexpressed genes IRAK1, CHEK1 and BUB1 may play an important role in ovarian cancer. We also show that these 17 genes can be used to form an ovarian cancer signature, to distinguish normal from ovarian cancer subjects and that the set of three genes, CHEK1, AR, and LYN, can be used to classify good and poor prognostic tumors.ConclusionWe provided a workflow using a Boolean logic schema for the identification of differentially expressed genes by integrating diverse biological information. This integrated approach resulted in the identification of genes as potential biomarkers in ovarian cancer.

GeneSetDB: A comprehensive meta-database, statistical and visualisation framework for gene set analysis

Most “omics” experiments require comprehensive interpretation of the biological meaning of gene lists. To address this requirement, a number of gene set analysis (GSA) tools have been developed. Although the biological value of GSA is strictly limited by the breadth of the gene sets used, very few methods exist for simultaneously analysing multiple publically available gene set databases. Therefore, we constructed GeneSetDB (http://genesetdb.auckland.ac.nz/haeremai.html), a comprehensive meta-database, which integrates 26 public databases containing diverse biological information with a particular focus on human disease and pharmacology. GeneSetDB enables users to search for gene sets containing a gene identifier or keyword, generate their own gene sets, or statistically test for enrichment of an uploaded gene list across all gene sets, and visualise gene set enrichment and overlap using a clustered heat map.

Plant MetGenMAP: An Integrative Analysis System for Plant Systems Biology

The information and resources generated from diverse "omics" technologies provide opportunities for producing novel biological knowledge. It is essential to integrate various kinds of biological information and large-scale omics data sets through systematic analysis in order to describe and understand complex biological phenomena. For this purpose, we have developed a Web-based system, Plant MetGenMAP, which can comprehensively integrate and analyze large-scale gene expression and metabolite profile data sets along with diverse biological information. Using this system, significantly altered biochemical pathways and biological processes under given conditions can be retrieved rapidly and efficiently, and transcriptional events and/or metabolic changes in a pathway can be easily visualized. In addition, the system provides a unique function that can identify candidate promoter motifs associated with the regulation of specific biochemical pathways. We demonstrate the functions and application of the system using data sets from Arabidopsis (Arabidopsis thaliana) and tomato (Solanum lycopersicum), respectively. The results obtained by Plant MetGenMAP can aid in a better understanding of the mechanisms that underlie interesting biological phenomena and provide novel insights into the biochemical changes associated with them at the gene and metabolite levels. Plant MetGenMAP is freely available at http://bioinfo.bti.cornell.edu/tool/MetGenMAP.

GeneCodis: interpreting gene lists through enrichment analysis and integration of diverse biological information

GeneCodis is a web server application for functional analysis of gene lists that integrates different sources of information and finds modular patterns of interrelated annotations. This integrative approach has proved to be useful for the interpretation of high-throughput experiments and therefore a new version of the system has been developed to expand its functionality and scope. GeneCodis now expands the functional information with regulatory patterns and user-defined annotations, offering the possibility of integrating all sources of information in the same analysis. Traditional singular enrichment is now permitted and more organisms and gene identifiers have been added to the database. The application has been re-engineered to improve performance, accessibility and scalability. In addition, GeneCodis can now be accessed through a public SOAP web services interface, enabling users to perform analysis from their own scripts and workflows. The application is freely available at http://genecodis.dacya.ucm.es

An efficient strategy for extensive integration of diverse biological data for protein function prediction

With the increasing availability of diverse biological information, protein function prediction approaches have converged towards integration of heterogeneous data. Many adapted existing techniques, such as machine-learning and probabilistic methods, which have proven successful on specific data types. However, the impact of these approaches is hindered by a couple of factors. First, there is little comparison between existing approaches. This is in part due to a divergence in the focus adopted by different works, which makes comparison difficult or even fuzzy. Second, there seems to be over-emphasis on the use of computationally demanding machine-learning methods, which runs counter to the surge in biological data. Analogous to the success of BLAST for sequence homology search, we believe that the ability to tap escalating quantity, quality and diversity of biological data is crucial to the success of automated function prediction as a useful instrument for the advancement of proteomic research. We address these problems by: (1) providing useful comparison between some prominent methods; (2) proposing Integrated Weighted Averaging (IWA)--a scalable, efficient and flexible function prediction framework that integrates diverse information using simple weighting strategies and a local prediction method. The simplicity of the approach makes it possible to make predictions based on on-the-fly information fusion. In addition to its greater efficiency, IWA performs exceptionally well against existing approaches. In the presence of cross-genome information, which is overwhelming for existing approaches, IWA makes even better predictions. We also demonstrate the significance of appropriate weighting strategies in data integration.

A fuzzy guided genetic algorithm for operon prediction

The operon structure of the prokaryotic genome is a critical input for the reconstruction of regulatory networks at the whole genome level. As experimental methods for the detection of operons are difficult and time-consuming, efforts are being put into developing computational methods that can use available biological information to predict operons. A genetic algorithm is developed to evolve a starting population of putative operon maps of the genome into progressively better predictions. Fuzzy scoring functions based on multiple criteria are used for assessing the 'fitness' of the newly evolved operon maps and guiding their evolution. The algorithm organizes the whole genome into operons. The fuzzy guided genetic algorithm-based approach makes it possible to use diverse biological information like genome sequence data, functional annotations and conservation across multiple genomes, to guide the organization process. This approach does not require any prior training with experimental operons. The predictions from this algorithm for Escherchia coli K12 and Bacillus subtilis are evaluated against experimentally discovered operons for these organisms. The accuracy of the method is evaluated using an ROC (receiver operating characteristic) analysis. The area under the ROC curve is around 0.9, which indicates excellent accuracy. roschen_csir@rediffmail.com.