Yeast Datasets Research Articles

Complex Prediction in Large PPI Networks Using Expansion and Stripe of Core Cliques.

The widespread availability and importance of large-scale protein-protein interaction (PPI) data demand a flurry of research efforts to understand the organisation of a cell and its functionality by analysing these data at the network level. In the bioinformatics and data mining fields, network clustering acquired a lot of attraction to examine a PPI network's topological and functional aspects. The clustering of PPI networks has been proven to be an excellent method for discovering functional modules, disclosing functions of unknown proteins, and other tasks in numerous research over the last decade. This research proposes a unique graph mining approach to detect protein complexes using dense neighbourhoods (highly connected regions) in an interaction graph. Our technique first finds size-3 cliques associated with each edge (protein interaction), and then these core cliques are expanded to form high-density subgraphs. Loosely connected proteins are stripped out from these subgraphs to produce a potential protein complex. Finally, the redundancy is removed based on the Jaccard coefficient. Computational results are presented on the yeast and human protein interaction dataset to highlight our proposed technique's efficiency. Predicted protein complexes of the proposed approach have a significantly higher score of similarity to those used as gold standards in the CYC-2008 and CORUM benchmark databases than other existing approaches.

MGEGFP: a multi-view graph embedding method for gene function prediction based on adaptive estimation with GCN.

In recent years, a number of computational approaches have been proposed to effectively integrate multiple heterogeneous biological networks, and have shown impressive performance for inferring gene function. However, the previous methods do not fully represent the critical neighborhood relationship between genes during the feature learning process. Furthermore, it is difficult to accurately estimate the contributions of different views for multi-view integration. In this paper, we propose MGEGFP, a multi-view graph embedding method based on adaptive estimation with Graph Convolutional Network (GCN), to learn high-quality gene representations among multiple interaction networks for function prediction. First, we design a dual-channel GCN encoder to disentangle the view-specific information and the consensus pattern across diverse networks. By the aid of disentangled representations, we develop a multi-gate module to adaptively estimate the contributions of different views during each reconstruction process and make full use of the multiplexity advantages, where a diversity preservation constraint is designed to prevent the over-fitting problem. To validate the effectiveness of our model, we conduct experiments on networks from the STRING database for both yeast and human datasets, and compare the performance with seven state-of-the-art methods in five evaluation metrics. Moreover, the ablation study manifests the important contribution of the designed dual-channel encoder, multi-gate module and the diversity preservation constraint in MGEGFP. The experimental results confirm the superiority of our proposed method and suggest that MGEGFP can be a useful tool for gene function prediction.

Predicting and explaining the impact of genetic disruptions and interactions on organismal viability.

MotivationExisting computational models can predict single- and double-mutant fitness but they do have limitations. First, they are often tested via evaluation metrics that are inappropriate for imbalanced datasets. Second, all of them only predict a binary outcome (viable or not, and negatively interacting or not). Third, most are uninterpretable black box machine learning models.ResultsBudding yeast datasets were used to develop high-performance Multinomial Regression (MN) models capable of predicting the impact of single, double and triple genetic disruptions on viability. These models are interpretable and give realistic non-binary predictions and can predict negative genetic interactions (GIs) in triple-gene knockouts. They are based on a limited set of gene features and their predictions are influenced by the probability of target gene participating in molecular complexes or pathways. Furthermore, the MN models have utility in other organisms such as fission yeast, fruit flies and humans, with the single gene fitness MN model being able to distinguish essential genes necessary for cell-autonomous viability from those required for multicellular survival. Finally, our models exceed the performance of previous models, without sacrificing interpretability.Availability and implementationAll code and processed datasets used to generate results and figures in this manuscript are available at our Github repository at https://github.com/KISRDevelopment/cell_viability_paper. The repository also contains a link to the GI prediction website that lets users search for GIs using the MN models.Supplementary information Supplementary data are available at Bioinformatics online.

SIPGCN: A Novel Deep Learning Model for Predicting Self-Interacting Proteins from Sequence Information Using Graph Convolutional Networks.

Protein is the basic organic substance that constitutes the cell and is the material condition for the life activity and the guarantee of the biological function activity. Elucidating the interactions and functions of proteins is a central task in exploring the mysteries of life. As an important protein interaction, self-interacting protein (SIP) has a critical role. The fast growth of high-throughput experimental techniques among biomolecules has led to a massive influx of available SIP data. How to conduct scientific research using the massive amount of SIP data has become a new challenge that is being faced in related research fields such as biology and medicine. In this work, we design an SIP prediction method SIPGCN using a deep learning graph convolutional network (GCN) based on protein sequences. First, protein sequences are characterized using a position-specific scoring matrix, which is able to describe the biological evolutionary message, then their hidden features are extracted by the deep learning method GCN, and, finally, the random forest is utilized to predict whether there are interrelationships between proteins. In the cross-validation experiment, SIPGCN achieved 93.65% accuracy and 99.64% specificity in the human data set. SIPGCN achieved 90.69% and 99.08% of these two indicators in the yeast data set, respectively. Compared with other feature models and previous methods, SIPGCN showed excellent results. These outcomes suggest that SIPGCN may be a suitable instrument for predicting SIP and may be a reliable candidate for future wet experiments.

A Novel Ensemble Learning-Based Computational Method to Predict Protein-Protein Interactions from Protein Primary Sequences.

Simple SummaryProtein–protein interactions (PPIs) play a central role in the evolution and progression of various biological processes. In this article, we constructed a novel ensemble-learning-based model to predict potential PPIs, which only utilized the protein sequence information. The presented method used Discrete Hilbert transform to extract amino acid sequence information from position-specific scoring matrices. Then these extracted features were fed into rotation forest for training and predicting. When applying our method to the three datasets (Yeast, Human, and Oryza sativa) for detecting PPIs, we obtained excellent prediction performance. Furthermore, the comparison results indicated that our computational model is effective and robust in predicting potential PPI pairs.Protein–protein interactions (PPIs) are crucial for understanding the cellular processes, including signal cascade, DNA transcription, metabolic cycles, and repair. In the past decade, a multitude of high-throughput methods have been introduced to detect PPIs. However, these techniques are time-consuming, laborious, and always suffer from high false negative rates. Therefore, there is a great need of new computational methods as a supplemental tool for PPIs prediction. In this article, we present a novel sequence-based model to predict PPIs that combines Discrete Hilbert transform (DHT) and Rotation Forest (RoF). This method contains three stages: firstly, the Position-Specific Scoring Matrices (PSSM) was adopted to transform the amino acid sequence into a PSSM matrix, which can contain rich information about protein evolution. Then, the 400-dimensional DHT descriptor was constructed for each protein pair. Finally, these feature descriptors were fed to the RoF classifier for identifying the potential PPI class. When exploring the proposed model on the Yeast, Human, and Oryza sativa PPIs datasets, it yielded excellent prediction accuracies of 91.93, 96.35, and 94.24%, respectively. In addition, we also conducted numerous experiments on cross-species PPIs datasets, and the predictive capacity of our method is also very excellent. To further access the prediction ability of the proposed approach, we present the comparison of RoF with four powerful classifiers, including Support Vector Machine (SVM), Random Forest (RF), K-nearest Neighbor (KNN), and AdaBoost. We also compared it with some existing superiority works. These comprehensive experimental results further confirm the excellent and feasibility of the proposed approach. In future work, we hope it can be a supplemental tool for the proteomics analysis.

DeepSimDEF: deep neural embeddings of gene products and gene ontology terms for functional analysis of genes.

MotivationThere is a plethora of measures to evaluate functional similarity (FS) of genes based on their co-expression, protein–protein interactions and sequence similarity. These measures are typically derived from hand-engineered and application-specific metrics to quantify the degree of shared information between two genes using their Gene Ontology (GO) annotations.ResultsWe introduce deepSimDEF, a deep learning method to automatically learn FS estimation of gene pairs given a set of genes and their GO annotations. deepSimDEF’s key novelty is its ability to learn low-dimensional embedding vector representations of GO terms and gene products and then calculate FS using these learned vectors. We show that deepSimDEF can predict the FS of new genes using their annotations: it outperformed all other FS measures by >5–10% on yeast and human reference datasets on protein–protein interactions, gene co-expression and sequence homology tasks. Thus, deepSimDEF offers a powerful and adaptable deep neural architecture that can benefit a wide range of problems in genomics and proteomics, and its architecture is flexible enough to support its extension to any organism.Availability and implementationSource code and data are available at https://github.com/ahmadpgh/deepSimDEFSupplementary information Supplementary data are available at Bioinformatics online.

Predicting Protein-Protein Interactions via Random Ferns with Evolutionary Matrix Representation

Protein-protein interactions (PPIs) play a crucial role in understanding disease pathogenesis, genetic mechanisms, guiding drug design, and other biochemical processes, thus, the identification of PPIs is of great importance. With the rapid development of high-throughput sequencing technology, a large amount of PPIs sequence data has been accumulated. Researchers have designed many experimental methods to detect PPIs by using these sequence data, hence, the prediction of PPIs has become a research hotspot in proteomics. However, since traditional experimental methods are both time-consuming and costly, it is difficult to analyze and predict the massive amount of PPI data quickly and accurately. To address these issues, many computational systems employing machine learning knowledge were widely applied to PPIs prediction, thereby improving the overall recognition rate. In this paper, a novel and efficient computational technology is presented to implement a protein interaction prediction system using only protein sequence information. First, the Position-Specific Iterated Basic Local Alignment Search Tool (PSI-BLAST) was employed to generate a position-specific scoring matrix (PSSM) containing protein evolutionary information from the initial protein sequence. Second, we used a novel data processing feature representation scheme, MatFLDA, to extract the essential information of PSSM for protein sequences and obtained five training and five testing datasets by adopting a five-fold cross-validation method. Finally, the random fern (RFs) classifier was employed to infer the interactions among proteins, and a model called MatFLDA_RFs was developed. The proposed MatFLDA_RFs model achieved good prediction performance with 95.03% average accuracy on Yeast dataset and 85.35% average accuracy on H. pylori dataset, which effectively outperformed other existing computational methods. The experimental results indicate that the proposed method is capable of yielding better prediction results of PPIs, which provides an effective tool for the detection of new PPIs and the in-depth study of proteomics. Finally, we also developed a web server for the proposed model to predict protein-protein interactions, which is freely accessible online at http://120.77.11.78:5001/webserver/MatFLDA_RFs.

Comparative Analysis of Unsupervised Protein Similarity Prediction Based on Graph Embedding.

The study of protein–protein interaction and the determination of protein functions are important parts of proteomics. Computational methods are used to study the similarity between proteins based on Gene Ontology (GO) to explore their functions and possible interactions. GO is a series of standardized terms that describe gene products from molecular functions, biological processes, and cell components. Previous studies on assessing the similarity of GO terms were primarily based on Information Content (IC) between GO terms to measure the similarity of proteins. However, these methods tend to ignore the structural information between GO terms. Therefore, considering the structural information of GO terms, we systematically analyze the performance of the GO graph and GO Annotation (GOA) graph in calculating the similarity of proteins using different graph embedding methods. When applied to the actual Human and Yeast datasets, the feature vectors of GO terms and proteins are learned based on different graph embedding methods. To measure the similarity of the proteins annotated by different GO numbers, we used Dynamic Time Warping (DTW) and cosine to calculate protein similarity in GO graph and GOA graph, respectively. Link prediction experiments were then performed to evaluate the reliability of protein similarity networks constructed by different methods. It is shown that graph embedding methods have obvious advantages over the traditional IC-based methods. We found that random walk graph embedding methods, in particular, showed excellent performance in calculating the similarity of proteins. By comparing link prediction experiment results from GO(DTW) and GOA(cosine) methods, it is shown that GO(DTW) features provide highly effective information for analyzing the similarity among proteins.

Prediction of Protein-Protein Interactions in Arabidopsis, Maize, and Rice by Combining Deep Neural Network With Discrete Hilbert Transform.

Protein–protein interactions (PPIs) in plants play an essential role in the regulation of biological processes. However, traditional experimental methods are expensive, time-consuming, and need sophisticated technical equipment. These drawbacks motivated the development of novel computational approaches to predict PPIs in plants. In this article, a new deep learning framework, which combined the discrete Hilbert transform (DHT) with deep neural networks (DNN), was presented to predict PPIs in plants. To be more specific, plant protein sequences were first transformed as a position-specific scoring matrix (PSSM). Then, DHT was employed to capture features from the PSSM. To improve the prediction accuracy, we used the singular value decomposition algorithm to decrease noise and reduce the dimensions of the feature descriptors. Finally, these feature vectors were fed into DNN for training and predicting. When performing our method on three plant PPI datasets Arabidopsis thaliana, maize, and rice, we achieved good predictive performance with average area under receiver operating characteristic curve values of 0.8369, 0.9466, and 0.9440, respectively. To fully verify the predictive ability of our method, we compared it with different feature descriptors and machine learning classifiers. Moreover, to further demonstrate the generality of our approach, we also test it on the yeast and human PPI dataset. Experimental results anticipated that our method is an efficient and promising computational model for predicting potential plant–protein interacted pairs.

Robust and accurate prediction of protein\u2013protein interactions by exploiting evolutionary information

Various biochemical functions of organisms are performed by protein–protein interactions (PPIs). Therefore, recognition of protein–protein interactions is very important for understanding most life activities, such as DNA replication and transcription, protein synthesis and secretion, signal transduction and metabolism. Although high-throughput technology makes it possible to generate large-scale PPIs data, it requires expensive cost of both time and labor, and leave a risk of high false positive rate. In order to formulate a more ingenious solution, biology community is looking for computational methods to quickly and efficiently discover massive protein interaction data. In this paper, we propose a computational method for predicting PPIs based on a fresh idea of combining orthogonal locality preserving projections (OLPP) and rotation forest (RoF) models, using protein sequence information. Specifically, the protein sequence is first converted into position-specific scoring matrices (PSSMs) containing protein evolutionary information by using the Position-Specific Iterated Basic Local Alignment Search Tool (PSI-BLAST). Then we characterize a protein as a fixed length feature vector by applying OLPP to PSSMs. Finally, we train an RoF classifier for the purpose of identifying non-interacting and interacting protein pairs. The proposed method yielded a significantly better results than existing methods, with 90.07% and 96.09% prediction accuracy on Yeast and Human datasets. Our experiment show the proposed method can serve as a useful tool to accelerate the process of solving key problems in proteomics.

APAL: Adjacency Propagation Algorithm for overlapping community detection in biological networks

We propose a novel method called Adjacency Propagation Algorithm (APAL) which considers the notion that the adjacent vertices are the best candidates for detecting overlapping communities in an undirected, unweighted, nontrivial graph. This is a compact algorithm with a single threshold parameter used to filter the detected communities according to their intraconnectivity property. In this study, APAL was tested rigorously using synthetic generators, such as the widely accepted LFR benchmark, as well as real data sets of yeast and human protein interactions networks. It was compared against the foremost algorithms in the field; the Clique Percolation Method (CPM), Community Overlap Propagation Algorithm (COPRA) and Neighbourhood-Inflated Seed Expansion (NISE). The results show that APAL outperforms its competitors for networks with increases in the number of memberships of the overlapping vertices. Such conditions are often found in biological networks, where a particular protein subunit may form part of several complexes. We believe that this shows the value of the implementation of APAL for protein interaction and other biological networks.

Integrating Elman recurrent neural network with particle swarm optimization algorithms for an improved hybrid training of multidisciplinary datasets

There are several types of neural networks (NNs) that are widely used for data classification tasks. The supervised learning NN is an advanced network with a training algorithm for setting the weights and biases of the network in its training phase. However, traditional training algorithms such as backpropagation have some drawbacks, such as slow convergence speed and falling into local minima, which reduces the performance of the classifier. Therefore, different nature-inspired metaheuristic algorithms are integrated with the NN training algorithms to provide derivative-free solutions for complex classification problems. Consequently, this paper proposes the integration of a particle swarm optimization (PSO) algorithm with an improved Elman recurrent neural network (ERNN) to form a PSO-ERNN metaheuristic model. The key contribution of this study is the development of a new dimensional equation for ERNN architecture and the integration of PSO in ERNN learning to produce the PSO-ERNN model. The PSO is constructed to train the NN and ERNN models to achieve a fast convergence rate and avoid local minima problems. The PSO-ERNN model is validated by comparing it against the standard PSO-NN metaheuristic model and similar models from the literature. The PSO-NN and PSO-ERNN models are tested and evaluated using ten benchmark classification problems of breast cancer, heart, hepatitis, liver, wine, iris, lung cancer, yeast, Pima Indians diabetes, and ionosphere datasets. In the training phase, the results show that the PSO-ERNN model performs better than the PSO-NN model when the training set has a bigger size of samples. In the testing phase, the PSO-ERNN model outperforms the PSO-NN model for all the tested datasets except the lung cancer and yeast datasets, in which the accuracy percentage slightly decreases. In the validation phase, the PSO-ERNN model shows better performance quality in terms of accuracy percentage in six of the tested datasets. The average percentage of the training, testing, and validation accumulation show that the PSO-NN performs better than the PSO-ERNN in the lung cancer (87.27, 83.32), and heart (73.56, 70.64) datasets. On the other hand, the PSO-ERNN performs better than the PSO-NN in the iris (88.18, 86.74), hepatitis (88.60, 87.93), wine (89.16, 86.08), liver (73.56, 70.64), ionosphere (83.98, 78.94), and breast cancer (94.84, 91.17). PSO-NN and PSO-ERNN produce the same average results in the Pima Indians diabetes (84.00, 84.00) and yeast (91.31, 91.30) dataset. These results show clearly that the PSO-ERNN generally outperforms the PSO-NN when considering the overall results of the ten datasets. Nevertheless, the combinations of the PSO-NN and PSO-ERNN are proven to represent consistent and robust classification methods. The computational efficiencies of the training processes in both the PSO-NN and PSO-ERNN models are highly improved when coupled with the PSO.

A New Sequential Forward Feature Selection (SFFS) Algorithm for Mining Best Topological and Biological Features to Predict Protein Complexes from Protein–Protein Interaction Networks (PPINs)

Protein-protein interaction plays an important role in the understanding of biological processes in the body. A network of dynamic protein complexes within a cell that regulates most biological processes is known as a protein-protein interaction network (PPIN). Complex prediction from PPINs is a challenging task. Most of the previous computation approaches mine cliques, stars, linear and hybrid structures as complexes from PPINs by considering topological features and fewer of them focus on important biological information contained within protein amino acid sequence. In this study, we have computed a wide variety of topological features and integrate them with biological features computed from protein amino acid sequence such as bag of words, physicochemical and spectral domain features. We propose a new Sequential Forward Feature Selection (SFFS) algorithm, i.e., random forest-based Boruta feature selection for selecting the best features from computed large feature set. Decision tree, linear discriminant analysis and gradient boosting classifiers are used as learners. We have conducted experiments by considering two reference protein complex datasets of yeast, i.e., CYC2008 and MIPS. Human and mouse complex information is taken from CORUM 3.0 dataset. Protein interaction information is extracted from the database of interacting proteins (DIP). Our proposed SFFS, i.e., random forest-based Brouta feature selection in combination with decision trees, linear discriminant analysis and Gradient Boosting Classifiers outperforms other state of art algorithms by achieving precision, recall and F-measure rates, i.e. 94.58%, 94.92% and 94.45% for MIPS, 96.31%, 93.55% and 96.02% for CYC2008, 98.84%, 98.00%, 98.87 % for CORUM humans and 96.60%, 96.70%, 96.32% for CORUM mouse dataset complexes, respectively.

Asexual Experimental Evolution of Yeast Does Not Curtail Transposable Elements.

Compared with asexual reproduction, sex facilitates the transmission of transposable elements (TEs) from one genome to another, but boosts the efficacy of selection against deleterious TEs. Thus, theoretically, it is unclear whether sex has a positive net effect on TE’s proliferation. An empirical study concluded that sex is at the root of TE’s evolutionary success because the yeast TE load was found to decrease rapidly in approximately 1,000 generations of asexual but not sexual experimental evolution. However, this finding contradicts the maintenance of TEs in natural yeast populations where sexual reproduction occurs extremely infrequently. Here, we show that the purported TE load reduction during asexual experimental evolution is likely an artifact of low genomic sequencing coverages. We observe stable TE loads in both sexual and asexual experimental evolution from multiple yeast data sets with sufficient coverages. To understand the evolutionary dynamics of yeast TEs, we turn to asexual mutation accumulation lines that have been under virtually no selection. We find that both TE transposition and excision rates per generation, but not their difference, tend to be higher in environments where yeast grows more slowly. However, the transposition rate is not significantly higher than the excision rate and the variance of the TE number among natural strains is close to its neutral expectation, suggesting that selection against TEs is at best weak in yeast. We conclude that the yeast TE load is maintained largely by a transposition–excision balance and that the influence of sex remains unclear.

Fuzzy Clustering Method Based on Improved Weighted Distance

As an essential data processing technology, cluster analysis has been widely used in various fields. In clustering, it is necessary to select appropriate measures to evaluate the similarity in the data. In this paper, firstly, a cluster center selection method based on the grey relational degree is proposed to solve the problem of sensitivity in initial cluster center selection. Secondly, combining the advantages of Euclidean distance, DTW distance, and SPDTW distance, a weighted distance measurement based on three kinds of reach is proposed. Then, it is applied to Fuzzy C-MeDOIDS and Fuzzy C-means hybrid clustering technology. Numerical experiments are carried out with the UCI datasets. The experimental results show that the accuracy of the clustering results is significantly improved by using the clustering method proposed in this paper. Besides, the method proposed in this paper is applied to the MUSIC INTO EMOTIONS and YEAST datasets. The clustering results show that the algorithm proposed in this paper can also achieve a better clustering effect when dealing with practical problems.

Self-Interacting Proteins Prediction from PSSM Based on Evolutionary Information

Self-interacting proteins (SIPs) play an influential role in regulating cell structure and function. Thus, it is critically important to identify whether proteins themselves interact with each other. Although there are some existing experimental methods for self-interaction recognition, the limitations of these methods are both expensive and time-consuming. Therefore, it is very necessary to develop an efficient and stable computational method for predicting SIPs. In this study, we develop an effective computational method for predicting SIPs based on rotation forest (RF) classifier, combined with histogram of oriented gradients (HOG) and synthetic minority oversampling technique (SMOTE). When performing SIPs prediction on yeast and human datasets, the proposed method achieves superior accuracies of 97.28% and 89.41%, respectively. In addition, the proposed approach was compared with the state-of-the-art support vector machine (SVM) classifiers and other different methods on the same datasets. The experimental results demonstrate that our method has good robustness and effectiveness and can be regarded as a useful tool for SIPs prediction.

Protein-Protein Interaction Prediction Based on Spectral Radius and General Regression Neural Network.

Protein-protein interaction (PPI) not only plays a critical role in cell life activities, but also plays an important role in discovering the mechanism of biological activity, protein function, and disease states. Developing computational methods is of great significance for PPIs prediction since experimental methods are time-consuming and laborious. In this paper, we proposed a PPI prediction algorithm called GRNN-PPI only using the amino acid sequence information based on general regression neural network and two feature extraction methods. Specifically, we designed a new feature extraction method named Mutation Spectral Radius (MSR) to extract evolutionary information by the BLOSUM62 matrix. Meanwhile, we integrated another feature extraction method, autocorrelation description, which can completely extract information on physicochemical properties and protein sequences. The principal component analysis was applied to eliminate noise, and the general regression neural network was adopted as a classifier. The prediction accuracy of the yeast, human, and Helicobacter pylori1 (H.pylori1) data sets were 97.47%, 99.63%, and 99.97%, respectively. In addition, we also conducted experiments on two important PPI networks and six independent data sets. All results were significantly higher than some state-of-the-art methods used for comparison, showing that our method is feasible and robust.

DPCMNE: Detecting Protein Complexes From Protein-Protein Interaction Networks Via Multi-Level Network Embedding.

Biological functions of a cell are typically carried out through protein complexes. The detection of protein complexes is therefore of great significance for understanding the cellular organizations and protein functions. In the past decades, many computational methods have been proposed to detect protein complexes. However, most of the existing methods just search the local topological information to mine dense subgraphs as protein complexes, ignoring the global topological information. To tackle this issue, we propose the DPCMNE method to detect protein complexes via multi-level network embedding. It can preserve both the local and global topological information of biological networks. First, DPCMNE employs a hierarchical compressing strategy to recursively compress the input protein-protein interaction (PPI) network into multi-level smaller PPI networks. Then, a network embedding method is applied on these smaller PPI networks to learn protein embeddings of different levels of granularity. The embeddings learned from all the compressed PPI networks are concatenated to represent the final protein embeddings of the original input PPI network. Finally, a core-attachment based strategy is adopted to detect protein complexes in the weighted PPI network constructed by the pairwise similarity of protein embeddings. To assess the efficiency of our proposed method, DPCMNE is compared with other eight clustering algorithms on two yeast datasets. The experimental results show that the performance of DPCMNE outperforms those state-of-the-art complex detection methods in terms of F1 and F1+Acc. Furthermore, the results of functional enrichment analysis indicate that protein complexes detected by DPCMNE are more biologically significant in terms of P-score.

Fully automated web-based tool for identifying regulatory hotspots

BackgroundRegulatory hotspots are genetic variations that may regulate the expression levels of many genes. It has been of great interest to find those hotspots utilizing expression quantitative trait locus (eQTL) analysis. However, it has been reported that many of the findings are spurious hotspots induced by various unknown confounding factors. Recently, methods utilizing complicated statistical models have been developed that successfully identify genuine hotspots. Next-generation Intersample Correlation Emended (NICE) is one of the methods that show high sensitivity and low false-discovery rate in finding regulatory hotspots. Even though the methods successfully find genuine hotspots, they have not been widely used due to their non-user-friendly interfaces and complex running processes. Furthermore, most of the methods are impractical due to their prohibitively high computational complexity.ResultsTo overcome the limitations of existing methods, we developed a fully automated web-based tool, referred to as NICER (NICE Renew), which is based on NICE program. First, we dramatically reduced running and installing burden of NICE. Second, we significantly reduced running time by incorporating multi-processing. Third, besides our web-based NICER, users can use NICER on Google Compute Engine and can readily install and run the NICER web service on their local computers. Finally, we provide different input formats and visualizations tools to show results. Utilizing a yeast dataset, we show that NICER can be successfully used in an eQTL analysis to identify many genuine regulatory hotspots, for which more than half of the hotspots were previously reported elsewhere.ConclusionsEven though many hotspot analysis tools have been proposed, they have not been widely used for many practical reasons. NICER is a fully-automated web-based solution for eQTL mapping and regulatory hotspots analysis. NICER provides a user-friendly interface and has made hotspot analysis more viable by reducing the running time significantly. We believe that NICER will become the method of choice for increasing power of eQTL hotspot analysis.

Inference of gene regulatory networks based on nonlinear ordinary differential equations.

Gene regulatory networks (GRNs) capture the regulatory interactions between genes, resulting from the fundamental biological process of transcription and translation. In some cases, the topology of GRNs is not known, and has to be inferred from gene expression data. Most of the existing GRNs reconstruction algorithms are either applied to time-series data or steady-state data. Although time-series data include more information about the system dynamics, steady-state data imply stability of the underlying regulatory networks. In this article, we propose a method for inferring GRNs from time-series and steady-state data jointly. We make use of a non-linear ordinary differential equations framework to model dynamic gene regulation and an importance measurement strategy to infer all putative regulatory links efficiently. The proposed method is evaluated extensively on the artificial DREAM4 dataset and two real gene expression datasets of yeast and Escherichia coli. Based on public benchmark datasets, the proposed method outperforms other popular inference algorithms in terms of overall score. By comparing the performance on the datasets with different scales, the results show that our method still keeps good robustness and accuracy at a low computational complexity. The proposed method is written in the Python language, and is available at: https://github.com/lab319/GRNs_nonlinear_ODEs. Supplementary data are available at Bioinformatics online.