Antimicrobial peptides (AMPs) have drawn the interest of the researchers since they offer an alternative to the traditional antibiotics in the fight against antibiotic resistance and they exhibit additional pharmaceutically significant properties. Recently, computational approaches attemp to reveal how antibacterial activity is determined from a machine learning perspective and they aim to search and find the biological cues or characteristics that control antimicrobial activity via incorporating motif match scores. This study is dedicated to the development of a machine learning framework aimed at devising novel antimicrobial peptide (AMP) sequences potentially effective against Gram-positive /Gram-negative bacteria. In order to design newly generated sequences classified as either AMP or non-AMP, various classification models were trained. These novel sequences underwent validation utilizing the "DBAASP:strain-specific antibacterial prediction based on machine learning approaches and data on AMP sequences" tool. The findings presented herein represent a significant stride in this computational research, streamlining the process of AMP creation or modification within wet lab environments.

Identifying disease-disease associations (DDAs) is critical in medicine and systems biology, providing valuable insights into the complex relationships among different diseases. Recent advances in systems biology and the increasing availability of diverse biological data have provided opportunities for such research. However, the heterogeneity of the data makes it difficult to identify disease associations. To develop effective methods for predicting DDAs, it is necessary to leverage data at the molecular level. In this study, utilizing the Grouping-Scoring-Modeling approach, we have developed a statistical technique to compute a semantic similarity metric between the disease under study and other diseases. We have also used Jaccard similarity to compute similarity among disease groups. We have considered GediNETPro, using machine learning techniques, to record, over the Monte Carlo cross-validation, all the ranks based on the scores assigned by the S component to each disease group. The K-means clustering algorithm is applied to these recorded ranks for each disease group to detect patterns of similar diseases by placing them into coherent clusters. A cluster score (named as cluster_score) is assigned for each cluster by averaging the ranks of its members. Notably, the lowest cluster score is the more significant one. The semantic approach is applied to the top-ranked clusters to detect a semantic relationship between the disease under investigation and other diseases (groups). In addition, we have applied diversity metrics based on the Jaccard measurement to each disease cluster to support the semantic findings. A high value of diversity indicates a greater likelihood of detecting distinct groups with semantic relationships. This study enhances our understanding of disease associations and increases our ability to improve treatment strategies. This is especially important in a context where disease associations go beyond the scope of genetic factors.

High throughput -omics technologies facilitate the investigation of regulatory mechanisms of complex diseases. Along this line, scientists develop promising tools and methods to extend our understanding at the molecular and functional levels. To this end, miRcorrNet tool performs integrative analysis of microRNA (miRNA) and gene expression profiles via machine learning (ML) approach to identify significant miRNA groups and their associated target genes. In this study, we propose miRcorrNetPro tool, which extends miRcorrNet by tracking group scoring, ranking and other information through the cross-validation iterations. Heatmap visualizations enable deep novel insights into the collective behavior of clusters of groups in cellular signaling and hence facilitate detection of potential biomarkers for the disease under investigation. Although miRcorrNetPro is designed as a generic tool, here we present our findings and potential miRNA biomarkers for Breast Cancer (BRCA). The miRcorrNetPro tool and all other supplementary files are available at https://github.com/Miray-Unlu/miRcorrNetPro.

BACKGROUND: Cell homeostasis relies on the concerted actions of genes, and dysregulated genes can lead to diseases. In living organisms, genes or their products do not act alone but within networks. Subsets of these networks can be viewed as modules that provide specific functionality to an organism. The Kyoto encyclopedia of genes and genomes (KEGG) systematically analyzes gene functions, proteins, and molecules and combines them into pathways. Measurements of gene expression (e.g., RNA-seq data) can be mapped to KEGG pathways to determine which modules are affected or dysregulated in the disease. However, genes acting in multiple pathways and other inherent issues complicate such analyses. Many current approaches may only employ gene expression data and need to pay more attention to some of the existing knowledge stored in KEGG pathways for detecting dysregulated pathways. New methods that consider more precompiled information are required for a more holistic association between gene expression and diseases. RESULTS: PriPath is a novel approach that transfers the generic process of grouping and scoring, followed by modeling to analyze gene expression with KEGG pathways. In PriPath, KEGG pathways are utilized as the grouping function as part of a machine learning algorithm for selecting the most significant KEGG pathways. A machine learning model is trained to differentiate between diseases and controls using those groups. We have tested PriPath on 13 gene expression datasets of various cancers and other diseases. Our proposed approach successfully assigned biologically and clinically relevant KEGG terms to the samples based on the differentially expressed genes. We have comparatively evaluated the performance of PriPath against other tools, which are similar in their merit. For each dataset, we manually confirmed the top results of PriPath in the literature and found that most predictions can be supported by previous experimental research. CONCLUSIONS: PriPath can thus aid in determining dysregulated pathways, which applies to medical diagnostics. In the future, we aim to advance this approach so that it can perform patient stratification based on gene expression and identify druggable targets. Thereby, we cover two aspects of precision medicine.

MOTIVATION: Disease is often manifested via changes in transcript and protein abundance. MicroRNAs (miRNAs) are instrumental in regulating protein abundance and may measurably influence transcript levels. miRNAs often target more than one mRNA (for humans, the average is three), and mRNAs are often targeted by more than one miRNA (for the genes considered in this study, the average is also three). Therefore, it is difficult to determine the miRNAs that may cause the observed differential gene expression. We present a novel approach, maTE, which is based on machine learning, that integrates information about miRNA target genes with gene expression data. maTE depends on the availability of a sufficient amount of patient and control samples. The samples are used to train classifiers to accurately classify the samples on a per miRNA basis. Multiple high scoring miRNAs are used to build a final classifier to improve separation. RESULTS: The aim of the study is to find a set of miRNAs causing the regulation of their target genes that best explains the difference between groups (e.g. cancer versus control). maTE provides a list of significant groups of genes where each group is targeted by a specific miRNA. For the datasets used in this study, maTE generally achieves an accuracy well above 80%. Also, the results show that when the accuracy is much lower (e.g. ∼50%), the set of miRNAs provided is likely not causative of the difference in expression. This new approach of integrating miRNA regulation with expression data yields powerful results and is independent of external labels and training data. Thereby, this approach allows new avenues for exploring miRNA regulation and may enable the development of miRNA-based biomarkers and drugs. AVAILABILITY AND IMPLEMENTATION: The KNIME workflow, implementing maTE, is available at Bioinformatics online. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Identification of essential genes is not only useful for our understanding of the minimal gene set required for cellular life but also aids the identification of novel drug targets in pathogens. In this work, we present a simple and effective gene essentiality prediction method using information-theoretic features that are derived exclusively from the gene sequences. RESULTS: We developed a Random Forest classifier and performed an extensive model performance evaluation among and within 15 selected bacteria. In intra-organism predictions, where training and testing sets are taken from the same organism, AUC (Area Under the Curve) scores ranging from 0.73 to 0.90, 0.84 on average, were obtained. Cross-organism predictions using 5-fold cross-validation, pairwise, leave-one-species-out, leave-one-taxon-out, and cross-taxon yielded average AUC scores of 0.88, 0.75, 0.80, 0.82, and 0.78, respectively. To further show the applicability of our method in other domains of life, we predicted the essential genes of the yeast Schizosaccharomyces pombe and obtained a similar accuracy (AUC 0.84). CONCLUSIONS: The proposed method enables a simple and reliable identification of essential genes without searching in databases for orthologs and demanding further experimental data such as network topology and gene-expression.

BACKGROUND: Post-transcriptional gene dysregulation can be a hallmark of diseases like cancer and microRNAs (miRNAs) play a key role in the modulation of translation efficiency. Known pre-miRNAs are listed in miRBase, and they have been discovered in a variety of organisms ranging from viruses and microbes to eukaryotic organisms. The computational detection of pre-miRNAs is of great interest, and such approaches usually employ machine learning to discriminate between miRNAs and other sequences. Many features have been proposed describing pre-miRNAs, and we have previously introduced the use of sequence motifs and k-mers as useful ones. There have been reports of xeno-miRNAs detected via next generation sequencing. However, they may be contaminations and to aid that important decision-making process, we aimed to establish a means to differentiate pre-miRNAs from different species. RESULTS: To achieve distinction into species, we used one species' pre-miRNAs as the positive and another species' pre-miRNAs as the negative training and test data for the establishment of machine learned models based on sequence motifs and k-mers as features. This approach resulted in higher accuracy values between distantly related species while species with closer relation produced lower accuracy values. CONCLUSIONS: We were able to differentiate among species with increasing success when the evolutionary distance increases. This conclusion is supported by previous reports of fast evolutionary changes in miRNAs since even in relatively closely related species a fairly good discrimination was possible.

BACKGROUND: Classification using microarray datasets is usually based on a small number of samples for which tens of thousands of gene expression measurements have been obtained. The selection of the genes most significant to the classification problem is a challenging issue in high dimension data analysis and interpretation. A previous study with SVM-RCE (Recursive Cluster Elimination), suggested that classification based on groups of correlated genes sometimes exhibits better performance than classification using single genes. Large databases of gene interaction networks provide an important resource for the analysis of genetic phenomena and for classification studies using interacting genes.We now demonstrate that an algorithm which integrates network information with recursive feature elimination based on SVM exhibits good performance and improves the biological interpretability of the results. We refer to the method as SVM with Recursive Network Elimination (SVM-RNE) RESULTS: Initially, one thousand genes selected by t-test from a training set are filtered so that only genes that map to a gene network database remain. The Gene Expression Network Analysis Tool (GXNA) is applied to the remaining genes to form n clusters of genes that are highly connected in the network. Linear SVM is used to classify the samples using these clusters, and a weight is assigned to each cluster based on its importance to the classification. The least informative clusters are removed while retaining the remainder for the next classification step. This process is repeated until an optimal classification is obtained. CONCLUSION: More than 90% accuracy can be obtained in classification of selected microarray datasets by integrating the interaction network information with the gene expression information from the microarrays.The Matlab version of SVM-RNE can be downloaded from http://web.macam.ac.il/~myousef.

SUMMARY: VISDA (Visual Statistical Data Analyzer) is a caBIG analytical tool for cluster modeling, visualization and discovery that has met silver-level compatibility under the caBIG initiative. Being statistically principled and visually interfaced, VISDA exploits both hierarchical statistics modeling and human gift for pattern recognition to allow a progressive yet interactive discovery of hidden clusters within high dimensional and complex biomedical datasets. The distinctive features of VISDA are particularly useful for users across the cancer research and broader research communities to analyze complex biological data. AVAILABILITY: http://gforge.nci.nih.gov/projects/visda/

MOTIVATION: Most computational methodologies for miRNA:mRNA target gene prediction use the seed segment of the miRNA and require cross-species sequence conservation in this region of the mRNA target. Methods that do not rely on conservation generate numbers of predictions, which are too large to validate. We describe a target prediction method (NBmiRTar) that does not require sequence conservation, using instead, machine learning by a naïve Bayes classifier. It generates a model from sequence and miRNA:mRNA duplex information from validated targets and artificially generated negative examples. Both the 'seed' and 'out-seed' segments of the miRNA:mRNA duplex are used for target identification. RESULTS: The application of machine-learning techniques to the features we have used is a useful and general approach for microRNA target gene prediction. Our technique produces fewer false positive predictions and fewer target candidates to be tested. It exhibits higher sensitivity and specificity than algorithms that rely on conserved genomic regions to decrease false positive predictions.

BACKGROUND: Classification studies using gene expression datasets are usually based on small numbers of samples and tens of thousands of genes. The selection of those genes that are important for distinguishing the different sample classes being compared, poses a challenging problem in high dimensional data analysis. We describe a new procedure for selecting significant genes as recursive cluster elimination (RCE) rather than recursive feature elimination (RFE). We have tested this algorithm on six datasets and compared its performance with that of two related classification procedures with RFE. RESULTS: We have developed a novel method for selecting significant genes in comparative gene expression studies. This method, which we refer to as SVM-RCE, combines K-means, a clustering method, to identify correlated gene clusters, and Support Vector Machines (SVMs), a supervised machine learning classification method, to identify and score (rank) those gene clusters for the purpose of classification. K-means is used initially to group genes into clusters. Recursive cluster elimination (RCE) is then applied to iteratively remove those clusters of genes that contribute the least to the classification performance. SVM-RCE identifies the clusters of correlated genes that are most significantly differentially expressed between the sample classes. Utilization of gene clusters, rather than individual genes, enhances the supervised classification accuracy of the same data as compared to the accuracy when either SVM or Penalized Discriminant Analysis (PDA) with recursive feature elimination (SVM-RFE and PDA-RFE) are used to remove genes based on their individual discriminant weights. CONCLUSION: SVM-RCE provides improved classification accuracy with complex microarray data sets when it is compared to the classification accuracy of the same datasets using either SVM-RFE or PDA-RFE. SVM-RCE identifies clusters of correlated genes that when considered together provide greater insight into the structure of the microarray data. Clustering genes for classification appears to result in some concomitant clustering of samples into subgroups. Our present implementation of SVM-RCE groups genes using the correlation metric. The success of the SVM-RCE method in classification suggests that gene interaction networks or other biologically relevant metrics that group genes based on functional parameters might also be useful.

MOTIVATION: Most computational methodologies for microRNA gene prediction utilize techniques based on sequence conservation and/or structural similarity. In this study we describe a new technique, which is applicable across several species, for predicting miRNA genes. This technique is based on machine learning, using the Naive Bayes classifier. It automatically generates a model from the training data, which consists of sequence and structure information of known miRNAs from a variety of species. RESULTS: Our study shows that the application of machine learning techniques, along with the integration of data from multiple species is a useful and general approach for miRNA gene prediction. Based on our experiments, we believe that this new technique is applicable to an extensive range of eukaryotes' genomes. Specific structure and sequence features are first used to identify miRNAs followed by a comparative analysis to decrease the number of false positives (FPs). The resulting algorithm exhibits higher specificity and similar sensitivity compared to currently used algorithms that rely on conserved genomic regions to decrease the rate of FPs.

In this paper, we show how a simple feed-forward neural network can be trained to filter documents when only positive information is available, and that this method seems to be superior to more standard methods, such as tf-idf retrieval based on an “average vector”. A novel experimental finding that retrieval is enhanced substantially in this context by carrying out a certain kind of uniform transformation (“Hadamard”) of the information prior to the training of the network.