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As an essential concept in attention, context defines the overall scope under consideration. In attention-based GNNs, context becomes the set of representation nodes of graph embedding. Current approaches choose immediate neighbors of the target or its subset as the context, which limits the ability of attention to capture long-distance dependency. To address this deficiency, we propose a novel attention-based GNN framework with extended contexts. Concretely, multi-hop nodes are first selected for context expansion according to information transferability and the number of hops. Then, to reduce the computational cost and fit the graph representation learning process, two heuristic context refinement policies are designed by focusing on local graph structure. One is for the graphs with high degrees, multi-hop neighbors with fewer connections to the target are removed to acquire accurate diffused information. The other is for the graphs with low degrees or uniform degree distribution, low-transferability neighbors are dislodged to ensure the graph locality is not obscured by the global information induced by the extended context. Finally, multi-head attention is employed in the refined context. Numerical comparisons with 23 baselines demonstrate the superiority of our method. Extensive model analysis shows that extending context with the informative multi-hop neighbors properly indeed promotes the performance of attention-based GNNs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this study, we explore how transformer models, which are known for their attention mechanisms, can improve pathogen prediction in pastured poultry farming. By combining farm management practices with microbiome data, our model outperforms traditional prediction methods in terms of the F1 score-an evaluation metric for model performance-thus fulfilling an essential need in predictive microbiology. Additionally, the emphasis is on making our model's predictions explainable. We introduce a novel approach for identifying feature importance using the model's attention matrix and the PageRank algorithm, offering insights that enhance our comprehension of established techniques such as DeepLIFT. Our results showcase the efficacy of transformer models in pathogen prediction for food safety and mark a noteworthy contribution to the progress of explainable AI within the biomedical sciences. This study sheds light on the impact of effective farm management practices and highlights the importance of technological advancements in ensuring food safety.

Image sentiment analysis technology can predict, measure and understand the emotional experience of human beings through images. Aiming at the problem of extracting emotional characteristics in art appreciation, this article puts forward an innovative method. Firstly, the PageRank algorithm is enhanced using tweet content similarity and time factors; secondly, the SE-ResNet network design is used to integrate Efficient Channel Attention (ECA) with the residual network structure, and ResNeXt50 is optimized to enhance the extraction of image sentiment features. Finally, the weight coefficients of overall emotions are dynamically adjusted to select a specific emotion incorporation strategy, resulting in effective bimodal fusion. The proposed model demonstrates exceptional performance in predicting sentiment labels, with maximum classification accuracy reaching 88.20%. The accuracy improvement of 21.34% compared to the traditional deep convolutional neural networks (DCNN) model attests to the effectiveness of this study. This research enriches images and texts' emotion feature extraction capabilities and improves the accuracy of emotion fusion classification., Competing Interests: The author has no conflict of interest., (© 2023 Yang and Chen.)

Climate risk is one of the key factors affecting the energy industry, and then affects the global energy trade. By adopting a network approach to the global energy trade and based on the data of global energy trade during 1996-2018, the evolution characteristics of the global energy trade network are hereby investigated, and the impact of climate risk on the global energy trade is explored. The results demonstrate that the global energy trade network has scale-free characteristics and significant regional characteristics and that its heterogeneity is weakening on the whole. Climate risk is negatively correlated with the energy trade relationship between countries. The simulation results show that climate risk has a greater impact on the import status of all countries than their export status and that only a few countries have large climate risk spillover effects. In addition, the climate risk spillover effects of countries are closely related to their import statuses. Overall, the present study provides policy suggestions for identifying important energy trading countries under climate risk shock and preventing the negative impact of climate risks on global energy trade., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Computational drug repositioning approaches are important, as they cost less compared to the traditional drug development processes. This study proposes a novel network-based drug repositioning approach, which computes similarities between disease-causing genes and drug-affected genes in a network topology to suggest candidate drugs with highest similarity scores. This new method aims to identify better treatment options by integrating systems biology approaches. It uses a protein-protein interaction network that is the main topology to compute a similarity score between candidate drugs and disease-causing genes. The disease-causing genes were mapped on this network structure. Transcriptome profiles of drug candidates were taken from the LINCS project and mapped individually on the network structure. The similarity of these two networks was calculated by different network neighborhood metrics, including Adamic-Adar, PageRank and neighborhood scoring. The proposed approach identifies the best candidates by choosing the drugs with significant similarity scores. The method was experimented on melanoma, colorectal, and prostate cancers. Several candidate drugs were predicted by applying AUC values of 0.6 or higher. Some of the predictions were approved by clinical phase trials or other in-vivo studies found in literature. The proposed drug repositioning approach would suggest better treatment options with integration of functional information between genes and transcriptome level effects of drug perturbations and diseases., Competing Interests: The authors declare there are no competing interests., (©2023 Cüvitoğlu and Isik.)

In this article, we propose a method for the automatic retrieval of a set of semantic primitive words from an explanatory dictionary and a novel evaluation procedure for the obtained set of primitives. The approach is based on the representation of the dictionary as a directed graph with a single-objective constrained optimization problem via a genetic algorithm with the PageRank scoring model. The problem is defined as a subset selection. The algorithm is fit to search for the sets of words that should fulfil several requirements: the cardinality of the set should not exceed empirically selected limits and the PageRank word importance score is minimized with cycle prevention thresholding. In the experiments, we used the WordNet dictionary for English. The proposed method is an improvement over the previous state-of-the-art solutions., Competing Interests: The authors declare there are no competing interests., (©2023 Kostiuk et al.)

Differential expression (DE) analysis has been routinely used to identify molecular features that are statistically significantly different between distinct biological groups. In recent years, differential network (DN) analysis has emerged as a powerful approach to uncover molecular network structure changes from one biological condition to the other where the molecular features with larger topological changes are selected as biomarkers. Although a large number of DE and a few DN-based methods are available, they have been usually implemented independently. DE analysis ignores the relationship among molecular features while DN analysis does not account for the expression changes at individual level. Therefore, an integrative analysis approach that accounts for both DE and DN is required to identify disease associated key features. Although, a handful of methods have been proposed, there is no method that optimizes the combination of DE and DN. We propose a novel integrative analysis method, DNrank, to identify disease-associated molecular features that leverages the strengths of both DE and DN by calculating a weight using resampling based cross validation scheme within the algorithm. First, differential expression analysis of individual molecular features is carried out. Second, a differential network structure is constructed using the differential partial correlation analysis. Third, the molecular features are ranked in the order of their significances by integrating their DE measures and DN structure using the modified Google's PageRank algorithm. In the algorithm, the optimum combination of DE and DN analyses is achieved by evaluating the prediction performance of top-ranked features utilizing support vector machine classifier with Monte Carlo cross validation. The proposed method is illustrated using both simulated data and three real data sets. The results show that the proposed method has a better performance in identifying important molecular features with respect to predictive discrimination. Also, as compared to existing feature selection methods, the top-ranked features selected by our method had a higher stability in selection. DNrank allows the researchers to identify the disease-associated features by utilizing both expression and network topology changes between two groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the United States. COPD represents one of many areas of research where identifying complex pathways and networks of interacting biomarkers is an important avenue toward studying disease progression and potentially discovering cures. Recently, sparse multiple canonical correlation network analysis (SmCCNet) was developed to identify complex relationships between omics associated with a disease phenotype, such as lung function. SmCCNet uses two sets of omics datasets and an associated output phenotypes to generate a multi-omics graph, which can then be used to explore relationships between omics in the context of a disease. Detecting significant subgraphs within this multi-omics network, i.e., subgraphs which exhibit high correlation to a disease phenotype and high inter-connectivity, can help clinicians identify complex biological relationships involved in disease progression. The current approach to identifying significant subgraphs relies on hierarchical clustering, which can be used to inform clinicians about important pathways involved in the disease or phenotype of interest. The reliance on a hierarchical clustering approach can hinder subgraph quality by biasing toward finding more compact subgraphs and removing larger significant subgraphs. This study aims to introduce new significant subgraph detection techniques. In particular, we introduce two subgraph detection methods, dubbed Correlated PageRank and Correlated Louvain, by extending the Personalized PageRank Clustering and Louvain algorithms, as well as a hybrid approach combining the two proposed methods, and compare them to the hierarchical method currently in use. The proposed methods show significant improvement in the quality of the subgraphs produced when compared to the current state of the art., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abdel-Hafiz, Najafi, Helmi, Pratte, Zhuang, Liu, Kechris, Bowler, Lange and Banaei-Kashani.)

Computing influential nodes gets a lot of attention from many researchers for information spreading in complex networks. It has vast applications, such as viral marketing, social leader creation, rumor control, and opinion monitoring. The information-spreading ability of influential nodes is greater compared with other nodes in the network. Several researchers proposed centrality measures to compute the influential nodes in a complex network, such as degree, betweenness, closeness, semi-local centralities, and PageRank. These centrality methods are defined based on the local and/or global information of nodes in the network. However, due to their high time complexity, centrality measures based on the global information of nodes have become unsuitable for large-scale networks. Very few centrality measures exist that are based on the attributes between nodes and the structure of the network. We propose the nearest neighborhood trust PageRank (NTPR) based on the structural attributes of neighbors and nearest neighbors of nodes. We define the measure based on the degree ratio, the similarity between nodes, the trust values of neighbors, and the nearest neighbors. We computed the influential nodes in various real-world networks using the proposed centrality method. We found the maximum influence by using influential nodes with SIR and independent cascade methods. We also compare the maximum influence of our centrality measure with the existing basic centrality measures.

Background: Cancer is a group of diseases that have received much attention in biological research because of its high mortality rate and the lack of accurate identification of its root causes. In such studies, researchers usually try to identify cancer driver genes (CDGs) that start cancer in a cell. The majority of the methods that have ever been proposed for the identification of CDGs are based on gene expression data and the concept of mutation in genomic data. Recently, using networking techniques and the concept of influence maximization, some models have been proposed to identify these genes., Objectives: We aimed to construct the cancer transcriptional regulatory network and identify cancer driver genes using a network science approach without the use of mutation and genomic data., Materials and Methods: In this study, we will employ the social influence network theory to identify CDGs in the human gene regulatory network (GRN) that is based on the concept of influence and power of webpages. First, we will create GRN Networks using gene expression data and Existing nodes and edges. Next, we will implement the modified algorithm on GRN networks being studied by weighting the regulatory interaction edges using the influence spread concept. Nodes with the highest ratings will be selected as the CDGs., Results: The results show our proposed method outperforms most of the other computational and network-based methods and show its superiority in identifying CDGs compared to many other methods. In addition, the proposed method can identify many CDGs that are overlooked by all previously published methods., Conclusions: Our study demonstrated that the Google's PageRank algorithm can be utilized and modified as a network-based method for identifying cancer driver gene in transcriptional regulatory network. Furthermore, the proposed method can be considered as a complementary method to the computational-based cancer driver gene identification tools., (Copyright: © 2021 The Author(s); Published by Iranian Journal of Biotechnology.)

We analyze how the COVID-19 pandemic affected the trade of products between countries. With this aim, using the United Nations Comtrade database, we perform a Google matrix analysis of the multiproduct World Trade Network (WTN) for the years 2018-2020, comprising the emergence of the COVID-19 as a global pandemic. The applied algorithms-PageRank, CheiRank and the reduced Google matrix-take into account the multiplicity of the WTN links, providing new insights into international trade compared to the usual import-export analysis. These complex networks analysis algorithms establish new rankings and trade balances of countries and products considering all countries on equal grounds, independent of their wealth, and every product on the basis of its relative exchanged volumes. In comparison with the pre-COVID-19 period, significant changes in these metrics occurred for the year 2020, highlighting a major rewiring of the international trade flows induced by the COVID-19 pandemic crisis. We define a new PageRank-CheiRank product trade balance, either export or import-oriented, which is significantly perturbed by the pandemic.

The ability to search for a part by its sequence is crucial for a large repository of parts. Prior to this work, however, this was not possible on SynBioHub. Sequence-based search is now integrated into SynBioHub, allowing users to find a part by a sequence provided in plain text or a supported file format. This sequence-based search feature is accessible to users via SynBioHub's web interface, or programmatically through its API. The core implementation of the tool uses VSEARCH, an open source, global alignment search tool, and it is integrated into SBOLExplorer, an open source distributed search engine used by SynBioHub. We present a new approach to scoring part similarity using SBOLExplorer, which takes into account both the popularity and percentage match of parts.

Ticks are blood-sucking parasites with different strategies of feeding depending on the tick family. The major families are Ixodidae or Argasidae, being slow or fast feeders, respectively. In the recent years, the advances in molecular sequencing techniques have enabled to gain knowledge about the proteome of the tick's salivary glands. But an holistic view of the biological processes underlying the expression of the sialome has been neglected. In this study we propose the use of standard biological processes as a tool to draw the physiology of the tick's salivary glands. We used published data on the sialome of Rhipicephalus sanguineus s.l. (Ixodidae) and Ornithodoros rostratus (Argasidae). A partial set of proteins obtained by these studies were used to define the biological process(es) in which proteins are involved. We used a directed network construction in which the nodes are proteins (source) and biological processes (target), separately for the low-level processes ("children") and the top-level ones ("parents"). We applied the method to feeding R. sanguineus at different time slices, and to different organs of O. rostratus . The network connects the proteins and the processes with a strength directly proportional to the transcript per millions of each protein. We used PageRank as a measure of the importance of each biological process. As suggested in previous studies, the sialome of unfed R. sanguineus express about 30% less biological processes than feeding ticks. Another decrease (25%) is noticed at the middle of the feeding and before detachment. However, top-level processes are deeply affected only at the onset of feeding, demonstrating a redundancy in the feeding. When ixodid-argasid are compared, large differences were observed: they do not share 91% of proteins, but share 90% of the biological processes. However, caution must be observed when examining these results. The hypothesis of different proteins linked to similar biological process(es) in both ticks is an extreme not confirmed in this study. Considering the limitations of this study, carried out with a selected set of proteins, we propose the networks of proteins of sialome linked to their biological processes as a tool aimed to explain the biological processes behind families of proteins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer LS declared a past co-authorship with one of the authors AE-P to the handling editor., (Copyright © 2022 Fernández-Ruiz and Estrada-Peña.)

In the era of big data, it is challenging to efficiently retrieve the required images from the vast amount of data. Therefore, a content-based image retrieval system is an important research direction to address this problem. Furthermore, a multi-feature-based image retrieval system can compensate for the shortage of a single feature to a certain extent, which is essential for improving retrieval system performance. Feature selection and feature fusion strategies are critical in the study of multi-feature fusion image retrieval. This paper proposes a multi-feature fusion image retrieval strategy with adaptive features based on information entropy theory. Firstly, we extract the image features, construct the distance function to calculate the similarity using the information entropy proposed in this paper, and obtain the initial retrieval results. Then, we obtain the precision of single feature retrieval based on the correlation feedback as the retrieval trust and use the retrieval trust to select the effective features automatically. After that, we initialize the weights of selected features using the average weights, construct the probability transfer matrix, and use the PageRank algorithm to update the initialized feature weights to obtain the final weights. Finally, we calculate the comprehensive similarity based on the final weights and output the detection results. This has two advantages: (1) the proposed strategy uses multiple features for image retrieval, which has better performance and more substantial generalization than the retrieval strategy based on a single feature; (2) compared with the fixed-feature retrieval strategy, our method selects the best features for fusion in each query, which takes full advantages of each feature. The experimental results show that our proposed method outperforms other methods. In the datasets of Corel1k, UC Merced Land-Use, and RSSCN7, the top10 retrieval precision is 99.55%, 88.02%, and 88.28%, respectively. In the Holidays dataset, the mean average precision (mAP) was 92.46%.

Identification of essential proteins is very important for understanding the basic requirements to sustain a living organism. In recent years, there has been an increasing interest in using computational methods to predict essential proteins based on protein-protein interaction (PPI) networks or fusing multiple biological information. However, it has been observed that existing PPI data have false-negative and false-positive data. The fusion of multiple biological information can reduce the influence of false data in PPI, but inevitably more noise data will be produced at the same time. In this article, we proposed a novel non-negative matrix tri-factorization (NMTF)-based model (NTMEP) to predict essential proteins. Firstly, a weighted PPI network is established only using the topology features of the network, so as to avoid more noise. To reduce the influence of false data (existing in PPI network) on performance of identify essential proteins, the NMTF technique, as a widely used recommendation algorithm, is performed to reconstruct a most optimized PPI network with more potential protein-protein interactions. Then, we use the PageRank algorithm to compute the final ranking score of each protein, in which subcellular localization and homologous information of proteins were used to calculate the initial scores. In addition, extensive experiments are performed on the publicly available datasets and the results indicate that our NTMEP model has better performance in predicting essential proteins against the start-of-the-art method. In this investigation, we demonstrated that the introduction of non-negative matrix tri-factorization technology can effectively improve the condition of the protein-protein interaction network, so as to reduce the negative impact of noise on the prediction. At the same time, this finding provides a more novel angle of view for other applications based on protein-protein interaction networks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Jiang, Wu, Zhang, Yan and Qu.)

Bovine viral diarrhea (BVD) caused by BVD virus (BVDV) leads to economic loss worldwide. Cattle that are persistently infected (PI) with BVDV are known to play an important role in viral transmission in association with the animal movement, as they shed the virus during their lifetime. In this research, the "hot spot" for BVD transmission was estimated by combining phylogenetic and epidemiological analyses for PI cattle and cattle that lived together on BVDV affected farms in Tokachi district, Hokkaido prefecture, Japan. Viral isolates were genetically categorized into BVDV-1a, 1b, and 2a, based on the nucleotide sequence of the entire E2 region. In BVDV genotype 1, subgenotype b (BVDV-1b), cluster I was identified as the majority in Tokachi district. Network analysis indicated that 12 of the 15 affected farms had cattle movements from other facilities (PI-network) and farms affected with BVDV-1b cluster I consisted of a large network. It was implied that the number of cattle movements themselves would be a risk of BVD transmission, using the PageRank algorithm. Therefore, these results demonstrate that cattle movements would contribute to disease spread and the combination of virological and epidemiological analysis methods would be beneficial in determining possible virus transmission routes.

As one of the most important tasks in protein structure prediction, protein fold recognition has attracted more and more attention. In this regard, some computational predictors have been proposed with the development of machine learning and artificial intelligence techniques. However, these existing computational methods are still suffering from some disadvantages. In this regard, we propose a new network-based predictor called ProtFold-DFG for protein fold recognition. We propose the Directed Fusion Graph (DFG) to fuse the ranking lists generated by different methods, which employs the transitive closure to incorporate more relationships among proteins and uses the KL divergence to calculate the relationship between two proteins so as to improve its generalization ability. Finally, the PageRank algorithm is performed on the DFG to accurately recognize the protein folds by considering the global interactions among proteins in the DFG. Tested on a widely used and rigorous benchmark data set, LINDAHL dataset, experimental results show that the ProtFold-DFG outperforms the other 35 competing methods, indicating that ProtFold-DFG will be a useful method for protein fold recognition. The source code and data of ProtFold-DFG can be downloaded from http://bliulab.net/ProtFold-DFG/download., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Online social media (OSM) has emerged as a prominent platform for debate on a wide range of issues. Even celebrities and public figures often share their opinions on a variety of topics through OSM platforms. One such subject that has gained a lot of coverage on Twitter is the Novel Coronavirus, officially known as COVID-19, which has become a pandemic and has sparked a crisis in human history. In this study, we examine 29 million tweets over three months to study highly influential users, whom we refer to as leaders. We recognize these leaders through social network techniques and analyse their tweets using text analysis. Using a community detection algorithm, we categorize these leaders into four clusters: research , news , health , and politics , with each cluster containing Twitter handles (accounts) of individual users or organizations. e.g., the health cluster includes the World Health Organization (@WHO), the Director-General of WHO (@DrTedros), and so on. The emotion analysis reveals that (i) all clusters show an equal amount of fear in their tweets, (ii) research and news clusters display more sadness than others, and (iii) health and politics clusters are attempting to win public trust . According to the text analysis, the (i) research cluster is more concerned with recognizing symptoms and the development of vaccination ; (ii) news and politics clusters are mostly concerned with travel . We then show that we can use our findings to classify tweets into clusters with a score of 96% AUC ROC., Competing Interests: Conflict interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature 2021.)

We apply the recently developed reduced Google matrix algorithm for the analysis of the OECD-WTO World Network of Economic Activities. This approach allows to determine interdependencies and interactions of economy sectors of several countries, including China, Russia and the USA, properly taking into account the influence of all the other world countries and their economic activities. Within this analysis, we also obtain the sensitivity of EU countries' economies to the petroleum activity sector. We show that this approach takes into account the multiplicity of economical interactions between countries and activity sectors, thus providing a richer analysis compared to the usual export-import analysis.

The Human Proteome Project (HPP) is leading the international effort to characterize the human proteome. Although the main goal of this project was first focused on the detection of missing proteins, a new challenge arose from the need to assign biological functions to the uncharacterized human proteins and describe their implications in human diseases. Not only the proteins with experimental evidence (uPE1 proteins) but also the uncharacterized missing proteins (uMPs) were the objects of study in this challenge, neXt-CP50. In this work, we developed a new bioinformatic approach to infer biological annotations for the uPE1 proteins and uMPs based on a "guilt-by-association" analysis using public RNA-Seq data sets. We used the correlation of these proteins with the well-characterized PE1 proteins to construct a network. In this way, we applied the PageRank algorithm to this network to identify the most relevant nodes, which were the biological annotations of the uncharacterized proteins. All of the generated information was stored in a database. In addition, we implemented the web application UPEFinder (https://upefinder.proteored.org) to facilitate the access to this new resource. This information is especially relevant for the researchers of the HPP who are interested in the generation and validation of new hypotheses about the functions of these proteins. Both the database and the web application are publicly available (https://github.com/ubioinformat/UPEfinder).

Background: Named Entity Linking systems are a powerful aid to the manual curation of digital libraries, which is getting increasingly costly and inefficient due to the information overload. Models based on the Personalized PageRank (PPR) algorithm are one of the state-of-the-art approaches, but these have low performance when the disambiguation graphs are sparse., Findings: This work proposes a Named Entity Linking framework designated by Relation Extraction for Entity Linking (REEL) that uses automatically extracted relations to overcome this limitation. Our method builds a disambiguation graph, where the nodes are the ontology candidates for the entities and the edges are added according to the relations established in the text, which the method extracts automatically. The PPR algorithm and the information content of each ontology are then applied to choose the candidate for each entity that maximises the coherence of the disambiguation graph. We evaluated the method on three gold standards: the subset of the CRAFT corpus with ChEBI annotations (CRAFT-ChEBI), the subset of the BC5CDR corpus with disease annotations from the MEDIC vocabulary (BC5CDR-Diseases) and the subset with chemical annotations from the CTD-Chemical vocabulary (BC5CDR-Chemicals). The F1-Score achieved by REEL was 85.8%, 80.9% and 90.3% in these gold standards, respectively, outperforming baseline approaches., Conclusions: We demonstrated that RE tools can improve Named Entity Linking by capturing semantic information expressed in text missing in Knowledge Bases and use it to improve the disambiguation graph of Named Entity Linking models. REEL can be adapted to any text mining pipeline and potentially to any domain, as long as there is an ontology or other knowledge Base available.

Type 2 diabetes has become one of the most serious diseases impairing people's life. Circulating miRNAs, involved in the development and progression of type 2 diabetes via different mechanisms, are considered a molecular marker for patients with type 2 diabetes. Based on the expression data of miRNAs in type 2 diabetes from the GEO database, our study screen out 5 differentially expressed candidate miRNAs through the interaction network between miRNAs and target genes and the protein interaction network (PPI) with random walk algorithm. Clinical newly diagnosed diabetic blood was recruited for further PCR experiments. Finally, miR-543 was significantly different, and its expression was up-regulated. miR-543 may become a new marker to bring forth innovation in individualized treatment of diabetes., Competing Interests: Declaration of competing interest This project has been approved by the Ethics Committee of the working institution and in accordance with the Helsinki Declaration (revised in Fortaleza, Brazil, October 2013). There is no conflict of interest in our study., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cisplatin is an antineoplastic drug administered at suboptimal and intermittent doses to avoid life-threatening effects. Although this regimen shortly improves symptoms in the short term, it also leads to more malignant disease in the long term. We describe a multilayered analysis ranging from chromatin to translation-integrating chromatin immunoprecipitation sequencing (ChIP-seq), global run-on sequencing (GRO-seq), RNA sequencing (RNA-seq), and ribosome profiling-to understand how cisplatin confers (pre)malignant features by using a well-established ovarian cancer model of cisplatin exposure. This approach allows us to segregate the human transcriptome into gene modules representing distinct regulatory principles and to characterize that the most cisplatin-disrupted modules are associated with underlying events of super-enhancer plasticity. These events arise when cancer cells initiate without ultimately ending the program of drug-stimulated death. Using a PageRank-based algorithm, we predict super-enhancer regulator ISL1 as a driver of this plasticity and validate this prediction by using CRISPR/dCas9-KRAB inhibition (CRISPRi) and CRISPR/dCas9-VP64 activation (CRISPRa) tools. Together, we propose that cisplatin reprograms cancer cells when inducing them to undergo near-to-death experiences., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

As one of the most important fundamental problems in protein sequence analysis, protein remote homology detection is critical for both theoretical research (protein structure and function studies) and real world applications (drug design). Although several computational predictors have been proposed, their detection performance is still limited. In this study, we treat protein remote homology detection as a document retrieval task, where the proteins are considered as documents and its aim is to find the highly related documents with the query documents in a database. A protein similarity network was constructed based on the true labels of proteins in the database, and the query proteins were then connected into the network based on the similarity scores calculated by three ranking methods, including PSI-BLAST, Hmmer and HHblits. The PageRank algorithm and Hyperlink-Induced Topic Search (HITS) algorithm were respectively performed on this network to move the homologous proteins of query proteins to the neighbors of the query proteins in the network. Finally, PageRank and HITS algorithms were combined, and a predictor called HITS-PR-HHblits was proposed to further improve the predictive performance. Tested on the SCOP and SCOPe benchmark datasets, the experimental results showed that the proposed protocols outperformed other state-of-the-art methods. For the convenience of the most experimental scientists, a web server for HITS-PR-HHblits was established at http://bioinformatics.hitsz.edu.cn/HITS-PR-HHblits, by which the users can easily get the results without the need to go through the mathematical details. The HITS-PR-HHblits predictor is a protocol for protein remote homology detection using different sets of programs, which will become a very useful computational tool for proteome analysis., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Minimizing post-operational neurological deficits as a result of brain surgery has been one of the most pertinent endeavours of neurosurgical research. Studies have utilised fMRIs, EEGs and MEGs in order to delineate and establish eloquent areas, however, these methods have not been utilized by the wider neurosurgical community due to a lack of clinical endpoints. We sought to ascertain if there is a correlation between graph theory metrics and the neurosurgical notion of eloquent brain regions. We also wanted to establish which graph theory based nodal centrality measure performs the best in predicting eloquent areas., Methods: We obtained diffusion neuroimaging data from the Human Connectome Project (HCP) and applied a parcellation scheme to it. This enabled us to construct a weighted adjacency matrix which we then analysed. Our analysis looked at the correlation between PageRank centrality and eloquent areas. We then compared PageRank centrality to eigenvector centrality and degree centrality to see what the best measure of empirical neurosurgical eloquence was., Results: Areas that are considered neurosurgically eloquent tended to be predicted by high PageRank centrality. By using summary scores for the three nodal centrality measures we found that PageRank centrality best correlated to empirical neurosurgical eloquence., Conclusion: The notion of eloquent areas is important to neurosurgery and graph theory provides a mathematical framework to predict these areas. PageRank centrality is able to consistently find areas that we consider eloquent. It is able to do so better than eigenvector and degree central measures.

This paper describes SBOLExplorer, a system that is used to provide intuitive searching within the SynBioHub genetic design repository. SynBioHub stores genetic constructs encoded in the SBOL data format. These constructs can represent genetic parts, circuits, and sequences. These constructs are often numerous, exist in various states of completeness and documentation, and do not lend themselves to simple searching and discovery. In particular, this paper focuses on improving the search capabilities of SynBioHub. Inspiration is drawn from the techniques used to organize and search over the World Wide Web, a linked data set with many of the same properties of the SBOL data in SynBioHub. SBOLExplorer integrates these methods into SynBioHub's data representation and search, providing significant improvement over the previous search implementation based on pattern-matching.

Accurate identification of prognostic biomarkers is an important yet challenging goal in bioinformatics. Many bioinformatics approaches have been proposed for this purpose, but there is still room for improvement. In this paper, we propose a novel machine learning-based method for more accurate identification of prognostic biomarker genes and use them for prediction of cancer prognosis. The proposed method specifies the candidate prognostic gene module by graph learning using the generative adversarial networks (GANs) model, and scores genes using a PageRank algorithm. We applied the proposed method to multiple-omics data that included copy number, gene expression, DNA methylation, and somatic mutation data for five cancer types. The proposed method showed better prediction accuracy than did existing methods. We identified many prognostic genes and their roles in their biological pathways. We also showed that the genes identified from different omics data were complementary, which led to improved accuracy in prediction using multi-omics data.

MicroRNAs (miRNAs) are small, non-coding RNAs involved in the regulation of gene expression at a post-transcriptional level. Recent studies have shown miRNAs as key regulators of a variety of biological processes, such as proliferation, differentiation, apoptosis, metabolism, etc. Aberrantly expressed miRNAs influence individual gene expression level, but rewired miRNA-mRNA connections can influence the activity of biological pathways. Here, we define rewired miRNA-mRNA connections as the differential (rewiring) effects on the activity of biological pathways between hepatocellular carcinoma (HCC) and normal phenotypes. Our work presented here uses a PageRank-based approach to measure the degree of miRNA-mediated dysregulation of biological pathways between HCC and normal samples based on rewired miRNA-mRNA connections. In our study, we regard the degree of miRNA-mediated dysregulation of biological pathways as disease risk of biological pathways. Therefore, we propose a new method, miR2Pathway, to measure and rank the degree of miRNA-mediated dysregulation of biological pathways by measuring the total differential influence of miRNAs on the activity of pathways between HCC and normal states. miR2Pathway proposed here systematically shows the first evidence for a mechanism of biological pathways being dysregulated by rewired miRNA-mRNA connections, and provides new insight into exploring mechanisms behind HCC. Thus, miR2Pathway is a novel method to identify and rank miRNA-dysregulated pathways in HCC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Complex diseases such as cancer are usually the result of a combination of environmental factors and one or several biological pathways consisting of sets of genes. Each biological pathway exerts its function by delivering signaling through the gene network. Theoretically, a pathway is supposed to have a robust topological structure under normal physiological conditions. However, the pathway's topological structure could be altered under some pathological condition. It is well known that a normal biological network includes a small number of well-connected hub nodes and a large number of nodes that are non-hubs. In addition, it is reported that the loss of connectivity is a common topological trait of cancer networks, which is an assumption of our method. Hence, from normal to cancer, the process of the network losing connectivity might be the process of disrupting the structure of the network, namely, the number of hub genes might be altered in cancer compared to that in normal or the distribution of topological ranks of genes might be altered. Based on this, we propose a new PageRank-based method called Pathways of Topological Rank Analysis (PoTRA) to detect pathways involved in cancer. We use PageRank to measure the relative topological ranks of genes in each biological pathway, then select hub genes for each pathway, and use Fisher's exact test to test if the number of hub genes in each pathway is altered from normal to cancer. Alternatively, if the distribution of topological ranks of gene in a pathway is altered between normal and cancer, this pathway might also be involved in cancer. Hence, we use the Kolmogorov-Smirnov test to detect pathways that have an altered distribution of topological ranks of genes between two phenotypes. We apply PoTRA to study hepatocellular carcinoma (HCC) and several subtypes of HCC. Very interestingly, we discover that all significant pathways in HCC are cancer-associated generally, while several significant pathways in subtypes of HCC are HCC subtype-associated specifically. In conclusion, PoTRA is a new approach to explore and discover pathways involved in cancer. PoTRA can be used as a complement to other existing methods to broaden our understanding of the biological mechanisms behind cancer at the system-level., Competing Interests: The authors declare there are no competing interests.

It is clear that the topological structure of a neural network somehow determines the activity of the neurons within it. In the present work, we ask to what extent it is possible to examine the structural features of a network and learn something about its activity? Specifically, we consider how the centrality (the importance of a node in a network) of a neuron correlates with its firing rate. To investigate, we apply an array of centrality measures, including In-Degree, Closeness, Betweenness, Eigenvector, Katz, PageRank, Hyperlink-Induced Topic Search (HITS) and NeuronRank to Leaky-Integrate and Fire neural networks with different connectivity schemes. We find that Katz centrality is the best predictor of firing rate given the network structure, with almost perfect correlation in all cases studied, which include purely excitatory and excitatory-inhibitory networks, with either homogeneous connections or a small-world structure. We identify the properties of a network which will cause this correlation to hold. We argue that the reason Katz centrality correlates so highly with neuronal activity compared to other centrality measures is because it nicely captures disinhibition in neural networks. In addition, we argue that these theoretical findings are applicable to neuroscientists who apply centrality measures to functional brain networks, as well as offer a neurophysiological justification to high level cognitive models which use certain centrality measures.

Methods for ranking the importance of nodes in a network have a rich history in machine learning and across domains that analyze structured data. Recent work has evaluated these methods through the "seed set expansion problem": given a subset [Formula: see text] of nodes from a community of interest in an underlying graph, can we reliably identify the rest of the community? We start from the observation that the most widely used techniques for this problem, personalized PageRank and heat kernel methods, operate in the space of "landing probabilities" of a random walk rooted at the seed set, ranking nodes according to weighted sums of landing probabilities of different length walks. Both schemes, however, lack an a priori relationship to the seed set objective. In this work, we develop a principled framework for evaluating ranking methods by studying seed set expansion applied to the stochastic block model. We derive the optimal gradient for separating the landing probabilities of two classes in a stochastic block model and find, surprisingly, that under reasonable assumptions the gradient is asymptotically equivalent to personalized PageRank for a specific choice of the PageRank parameter [Formula: see text] that depends on the block model parameters. This connection provides a formal motivation for the success of personalized PageRank in seed set expansion and node ranking generally. We use this connection to propose more advanced techniques incorporating higher moments of landing probabilities; our advanced methods exhibit greatly improved performance, despite being simple linear classification rules, and are even competitive with belief propagation., Competing Interests: The authors declare no conflict of interest.

This paper presents a novel model of science funding that exploits the wisdom of the scientific crowd. Each researcher receives an equal, unconditional part of all available science funding on a yearly basis, but is required to individually donate to other scientists a given fraction of all they receive. Science funding thus moves from one scientist to the next in such a way that scientists who receive many donations must also redistribute the most. As the funding circulates through the scientific community it is mathematically expected to converge on a funding distribution favored by the entire scientific community. This is achieved without any proposal submissions or reviews. The model furthermore funds scientists instead of projects, reducing much of the overhead and bias of the present grant peer review system. Model validation using large-scale citation data and funding records over the past 20 years show that the proposed model could yield funding distributions that are similar to those of the NSF and NIH, and the model could potentially be more fair and more equitable. We discuss possible extensions of this approach as well as science policy implications., Competing Interests: Competing interest The authors declare that they have no competing financial interest.

The simultaneous measurement of thousands of genes gives the opportunity to personalize and improve cancer therapy. In addition, the integration of meta-data such as protein-protein interaction (PPI) information into the analyses helps in the identification and prioritization of genes from these screens. Here, we describe a computational approach that identifies genes prognostic for outcome by combining gene profiling data from any source with a network of known relationships between genes.

Background: Personalized cancer treatments depend on the determination of a patient's genetic status according to known genetic profiles for which targeted treatments exist. Such genetic profiles must be scientifically validated before they is applied to general patient population. Reproducibility of findings that support such genetic profiles is a fundamental challenge in validation studies. The percentage of overlapping genes (POG) criterion and derivative methods produce unstable and misleading results. Furthermore, in a complex disease, comparisons between different tumor subtypes can produce high POG scores that do not capture the consistencies in the functions., Results: We focused on the quality rather than the quantity of the overlapping genes. We defined the rank value of each gene according to importance or quality by PageRank on basis of a particular topological structure. Then, we used the p-value of the rank-sum of the overlapping genes (PRSOG) to evaluate the quality of reproducibility. Though the POG scores were low in different studies of the same disease, the PRSOG was statistically significant, which suggests that sets of differentially expressed genes might be highly reproducible., Conclusions: Evaluations of eight datasets from breast cancer, lung cancer and four other disorders indicate that quality-based PRSOG method performs better than a quantity-based method. Our analysis of the components of the sets of overlapping genes supports the utility of the PRSOG method.

Background: Optimal ranking of literature importance is vital in overcoming article overload. Existing ranking methods are typically based on raw citation counts, giving a sum of 'inbound' links with no consideration of citation importance. PageRank, an algorithm originally developed for ranking webpages at the search engine, Google, could potentially be adapted to bibliometrics to quantify the relative importance weightings of a citation network. This article seeks to validate such an approach on the freely available, PubMed Central open access subset (PMC-OAS) of biomedical literature., Results: On-demand cloud computing infrastructure was used to extract a citation network from over 600,000 full-text PMC-OAS articles. PageRanks and citation counts were calculated for each node in this network. PageRank is highly correlated with citation count (R = 0.905, P < 0.01) and we thus validate the former as a surrogate of literature importance. Furthermore, the algorithm can be run in trivial time on cheap, commodity cluster hardware, lowering the barrier of entry for resource-limited open access organisations., Conclusions: PageRank can be trivially computed on commodity cluster hardware and is linearly correlated with citation count. Given its putative benefits in quantifying relative importance, we suggest it may enrich the citation network, thereby overcoming the existing inadequacy of citation counts alone. We thus suggest PageRank as a feasible supplement to, or replacement of, existing bibliometric ranking methods.

Diabetes is a growing concern for the developed nations worldwide. New genomic, metagenomic and gene-technologic approaches may yield considerable results in the next several years in its early diagnosis, or in advances in therapy and management. In this work, we highlight some human proteins that may serve as new targets in the early diagnosis and therapy. With the help of a very successful mathematical tool for network analysis that formed the basis of the early successes of Google(TM), Inc., we analyse the human protein-protein interaction network gained from the IntAct database with a mathematical algorithm. The novelty of our approach is that the new protein targets suggested do not have many interacting partners (so, they are not hubs or super-hubs), so their inhibition or promotion probably will not have serious side effects. We have identified numerous possible protein targets for diabetes therapy and/or management; some of these have been well known for a long time (these validate our method), some of them appeared in the literature in the last 12 months (these show the cutting edge of the algorithm), and the remainder are still unknown to be connected with diabetes, witnessing completely new hits of the method.

Disease progression in cancer can vary substantially between patients. Yet, patients often receive the same treatment. Recently, there has been much work on predicting disease progression and patient outcome variables from gene expression in order to personalize treatment options. Despite first diagnostic kits in the market, there are open problems such as the choice of random gene signatures or noisy expression data. One approach to deal with these two problems employs protein-protein interaction networks and ranks genes using the random surfer model of Google's PageRank algorithm. In this work, we created a benchmark dataset collection comprising 25 cancer outcome prediction datasets from literature and systematically evaluated the use of networks and a PageRank derivative, NetRank, for signature identification. We show that the NetRank performs significantly better than classical methods such as fold change or t-test. Despite an order of magnitude difference in network size, a regulatory and protein-protein interaction network perform equally well. Experimental evaluation on cancer outcome prediction in all of the 25 underlying datasets suggests that the network-based methodology identifies highly overlapping signatures over all cancer types, in contrast to classical methods that fail to identify highly common gene sets across the same cancer types. Integration of network information into gene expression analysis allows the identification of more reliable and accurate biomarkers and provides a deeper understanding of processes occurring in cancer development and progression., (© The Author 2012. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)