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1.
Brief Bioinform ; 25(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38426326

RESUMEN

Herbs applicability in disease treatment has been verified through experiences over thousands of years. The understanding of herb-disease associations (HDAs) is yet far from complete due to the complicated mechanism inherent in multi-target and multi-component (MTMC) botanical therapeutics. Most of the existing prediction models fail to incorporate the MTMC mechanism. To overcome this problem, we propose a novel dual-channel hypergraph convolutional network, namely HGHDA, for HDA prediction. Technically, HGHDA first adopts an autoencoder to project components and target protein onto a low-dimensional latent space so as to obtain their embeddings by preserving similarity characteristics in their original feature spaces. To model the high-order relations between herbs and their components, we design a channel in HGHDA to encode a hypergraph that describes the high-order patterns of herb-component relations via hypergraph convolution. The other channel in HGHDA is also established in the same way to model the high-order relations between diseases and target proteins. The embeddings of drugs and diseases are then aggregated through our dual-channel network to obtain the prediction results with a scoring function. To evaluate the performance of HGHDA, a series of extensive experiments have been conducted on two benchmark datasets, and the results demonstrate the superiority of HGHDA over the state-of-the-art algorithms proposed for HDA prediction. Besides, our case study on Chuan Xiong and Astragalus membranaceus is a strong indicator to verify the effectiveness of HGHDA, as seven and eight out of the top 10 diseases predicted by HGHDA for Chuan-Xiong and Astragalus-membranaceus, respectively, have been reported in literature.


Asunto(s)
Algoritmos , Astragalus propinquus , Benchmarking , Carbamatos
2.
Brief Bioinform ; 24(1)2023 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-36562706

RESUMEN

As microRNAs (miRNAs) are involved in many essential biological processes, their abnormal expressions can serve as biomarkers and prognostic indicators to prevent the development of complex diseases, thus providing accurate early detection and prognostic evaluation. Although a number of computational methods have been proposed to predict miRNA-disease associations (MDAs) for further experimental verification, their performance is limited primarily by the inadequacy of exploiting lower order patterns characterizing known MDAs to identify missing ones from MDA networks. Hence, in this work, we present a novel prediction model, namely HiSCMDA, by incorporating higher order network structures for improved performance of MDA prediction. To this end, HiSCMDA first integrates miRNA similarity network, disease similarity network and MDA network to preserve the advantages of all these networks. After that, it identifies overlapping functional modules from the integrated network by predefining several higher order connectivity patterns of interest. Last, a path-based scoring function is designed to infer potential MDAs based on network paths across related functional modules. HiSCMDA yields the best performance across all datasets and evaluation metrics in the cross-validation and independent validation experiments. Furthermore, in the case studies, 49 and 50 out of the top 50 miRNAs, respectively, predicted for colon neoplasms and lung neoplasms have been validated by well-established databases. Experimental results show that rich higher order organizational structures exposed in the MDA network gain new insight into the MDA prediction based on higher order connectivity patterns.


Asunto(s)
Neoplasias del Colon , Neoplasias Pulmonares , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Biología Computacional/métodos , Neoplasias Pulmonares/genética , Bases de Datos Factuales , Algoritmos , Predisposición Genética a la Enfermedad
3.
Brief Bioinform ; 23(3)2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35453147

RESUMEN

Drug-drug interactions (DDIs) are known as the main cause of life-threatening adverse events, and their identification is a key task in drug development. Existing computational algorithms mainly solve this problem by using advanced representation learning techniques. Though effective, few of them are capable of performing their tasks on biomedical knowledge graphs (KGs) that provide more detailed information about drug attributes and drug-related triple facts. In this work, an attention-based KG representation learning framework, namely DDKG, is proposed to fully utilize the information of KGs for improved performance of DDI prediction. In particular, DDKG first initializes the representations of drugs with their embeddings derived from drug attributes with an encoder-decoder layer, and then learns the representations of drugs by recursively propagating and aggregating first-order neighboring information along top-ranked network paths determined by neighboring node embeddings and triple facts. Last, DDKG estimates the probability of being interacting for pairwise drugs with their representations in an end-to-end manner. To evaluate the effectiveness of DDKG, extensive experiments have been conducted on two practical datasets with different sizes, and the results demonstrate that DDKG is superior to state-of-the-art algorithms on the DDI prediction task in terms of different evaluation metrics across all datasets.


Asunto(s)
Redes Neurales de la Computación , Reconocimiento de Normas Patrones Automatizadas , Algoritmos , Interacciones Farmacológicas , Bases del Conocimiento
4.
Brief Bioinform ; 23(1)2022 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-34965582

RESUMEN

The outbreak of COVID-19 caused by SARS-coronavirus (CoV)-2 has made millions of deaths since 2019. Although a variety of computational methods have been proposed to repurpose drugs for treating SARS-CoV-2 infections, it is still a challenging task for new viruses, as there are no verified virus-drug associations (VDAs) between them and existing drugs. To efficiently solve the cold-start problem posed by new viruses, a novel constrained multi-view nonnegative matrix factorization (CMNMF) model is designed by jointly utilizing multiple sources of biological information. With the CMNMF model, the similarities of drugs and viruses can be preserved from their own perspectives when they are projected onto a unified latent feature space. Based on the CMNMF model, we propose a deep learning method, namely VDA-DLCMNMF, for repurposing drugs against new viruses. VDA-DLCMNMF first initializes the node representations of drugs and viruses with their corresponding latent feature vectors to avoid a random initialization and then applies graph convolutional network to optimize their representations. Given an arbitrary drug, its probability of being associated with a new virus is computed according to their representations. To evaluate the performance of VDA-DLCMNMF, we have conducted a series of experiments on three VDA datasets created for SARS-CoV-2. Experimental results demonstrate that the promising prediction accuracy of VDA-DLCMNMF. Moreover, incorporating the CMNMF model into deep learning gains new insight into the drug repurposing for SARS-CoV-2, as the results of molecular docking experiments reveal that four antiviral drugs identified by VDA-DLCMNMF have the potential ability to treat SARS-CoV-2 infections.


Asunto(s)
Antivirales , Tratamiento Farmacológico de COVID-19 , COVID-19 , Aprendizaje Profundo , Reposicionamiento de Medicamentos , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Antivirales/química , Antivirales/farmacocinética , COVID-19/metabolismo , Humanos , SARS-CoV-2/química , SARS-CoV-2/metabolismo
5.
Brief Bioinform ; 23(1)2022 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-34891172

RESUMEN

Identifying new indications for drugs plays an essential role at many phases of drug research and development. Computational methods are regarded as an effective way to associate drugs with new indications. However, most of them complete their tasks by constructing a variety of heterogeneous networks without considering the biological knowledge of drugs and diseases, which are believed to be useful for improving the accuracy of drug repositioning. To this end, a novel heterogeneous information network (HIN) based model, namely HINGRL, is proposed to precisely identify new indications for drugs based on graph representation learning techniques. More specifically, HINGRL first constructs a HIN by integrating drug-disease, drug-protein and protein-disease biological networks with the biological knowledge of drugs and diseases. Then, different representation strategies are applied to learn the features of nodes in the HIN from the topological and biological perspectives. Finally, HINGRL adopts a Random Forest classifier to predict unknown drug-disease associations based on the integrated features of drugs and diseases obtained in the previous step. Experimental results demonstrate that HINGRL achieves the best performance on two real datasets when compared with state-of-the-art models. Besides, our case studies indicate that the simultaneous consideration of network topology and biological knowledge of drugs and diseases allows HINGRL to precisely predict drug-disease associations from a more comprehensive perspective. The promising performance of HINGRL also reveals that the utilization of rich heterogeneous information provides an alternative view for HINGRL to identify novel drug-disease associations especially for new diseases.


Asunto(s)
Servicios de Información , Aprendizaje Automático , Preparaciones Farmacéuticas , Algoritmos , Biología Computacional/métodos , Enfermedad , Reposicionamiento de Medicamentos/métodos , Humanos , Modelos Teóricos , Redes Neurales de la Computación
6.
Brief Bioinform ; 23(6)2022 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-36125202

RESUMEN

Drug repositioning (DR) is a promising strategy to discover new indicators of approved drugs with artificial intelligence techniques, thus improving traditional drug discovery and development. However, most of DR computational methods fall short of taking into account the non-Euclidean nature of biomedical network data. To overcome this problem, a deep learning framework, namely DDAGDL, is proposed to predict drug-drug associations (DDAs) by using geometric deep learning (GDL) over heterogeneous information network (HIN). Incorporating complex biological information into the topological structure of HIN, DDAGDL effectively learns the smoothed representations of drugs and diseases with an attention mechanism. Experiment results demonstrate the superior performance of DDAGDL on three real-world datasets under 10-fold cross-validation when compared with state-of-the-art DR methods in terms of several evaluation metrics. Our case studies and molecular docking experiments indicate that DDAGDL is a promising DR tool that gains new insights into exploiting the geometric prior knowledge for improved efficacy.


Asunto(s)
Aprendizaje Profundo , Reposicionamiento de Medicamentos , Reposicionamiento de Medicamentos/métodos , Inteligencia Artificial , Simulación del Acoplamiento Molecular , Servicios de Información , Algoritmos , Biología Computacional/métodos
7.
Brief Bioinform ; 23(3)2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35511108

RESUMEN

MOTIVATION: Interaction between transcription factor (TF) and its target genes establishes the knowledge foundation for biological researches in transcriptional regulation, the number of which is, however, still limited by biological techniques. Existing computational methods relevant to the prediction of TF-target interactions are mostly proposed for predicting binding sites, rather than directly predicting the interactions. To this end, we propose here a graph attention-based autoencoder model to predict TF-target gene interactions using the information of the known TF-target gene interaction network combined with two sequential and chemical gene characters, considering that the unobserved interactions between transcription factors and target genes can be predicted by learning the pattern of the known ones. To the best of our knowledge, the proposed model is the first attempt to solve this problem by learning patterns from the known TF-target gene interaction network. RESULTS: In this paper, we formulate the prediction task of TF-target gene interactions as a link prediction problem on a complex knowledge graph and propose a deep learning model called GraphTGI, which is composed of a graph attention-based encoder and a bilinear decoder. We evaluated the prediction performance of the proposed method on a real dataset, and the experimental results show that the proposed model yields outstanding performance with an average AUC value of 0.8864 +/- 0.0057 in the 5-fold cross-validation. It is anticipated that the GraphTGI model can effectively and efficiently predict TF-target gene interactions on a large scale. AVAILABILITY: Python code and the datasets used in our studies are made available at https://github.com/YanghanWu/GraphTGI.


Asunto(s)
Redes Neurales de la Computación
8.
Brief Bioinform ; 23(3)2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35323894

RESUMEN

While the technologies of ribonucleic acid-sequence (RNA-seq) and transcript assembly analysis have continued to improve, a novel topology of RNA transcript was uncovered in the last decade and is called circular RNA (circRNA). Recently, researchers have revealed that they compete with messenger RNA (mRNA) and long noncoding for combining with microRNA in gene regulation. Therefore, circRNA was assumed to be associated with complex disease and discovering the relationship between them would contribute to medical research. However, the work of identifying the association between circRNA and disease in vitro takes a long time and usually without direction. During these years, more and more associations were verified by experiments. Hence, we proposed a computational method named identifying circRNA-disease association based on graph representation learning (iGRLCDA) for the prediction of the potential association of circRNA and disease, which utilized a deep learning model of graph convolution network (GCN) and graph factorization (GF). In detail, iGRLCDA first derived the hidden feature of known associations between circRNA and disease using the Gaussian interaction profile (GIP) kernel combined with disease semantic information to form a numeric descriptor. After that, it further used the deep learning model of GCN and GF to extract hidden features from the descriptor. Finally, the random forest classifier is introduced to identify the potential circRNA-disease association. The five-fold cross-validation of iGRLCDA shows strong competitiveness in comparison with other excellent prediction models at the gold standard data and achieved an average area under the receiver operating characteristic curve of 0.9289 and an area under the precision-recall curve of 0.9377. On reviewing the prediction results from the relevant literature, 22 of the top 30 predicted circRNA-disease associations were noted in recent published papers. These exceptional results make us believe that iGRLCDA can provide reliable circRNA-disease associations for medical research and reduce the blindness of wet-lab experiments.


Asunto(s)
MicroARNs , ARN Circular , Algoritmos , Biología Computacional/métodos , MicroARNs/genética , Curva ROC
9.
Bioinformatics ; 39(8)2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37505483

RESUMEN

MOTIVATION: The task of predicting drug-target interactions (DTIs) plays a significant role in facilitating the development of novel drug discovery. Compared with laboratory-based approaches, computational methods proposed for DTI prediction are preferred due to their high-efficiency and low-cost advantages. Recently, much attention has been attracted to apply different graph neural network (GNN) models to discover underlying DTIs from heterogeneous biological information network (HBIN). Although GNN-based prediction methods achieve better performance, they are prone to encounter the over-smoothing simulation when learning the latent representations of drugs and targets with their rich neighborhood information in HBIN, and thereby reduce the discriminative ability in DTI prediction. RESULTS: In this work, an improved graph representation learning method, namely iGRLDTI, is proposed to address the above issue by better capturing more discriminative representations of drugs and targets in a latent feature space. Specifically, iGRLDTI first constructs an HBIN by integrating the biological knowledge of drugs and targets with their interactions. After that, it adopts a node-dependent local smoothing strategy to adaptively decide the propagation depth of each biomolecule in HBIN, thus significantly alleviating over-smoothing by enhancing the discriminative ability of feature representations of drugs and targets. Finally, a Gradient Boosting Decision Tree classifier is used by iGRLDTI to predict novel DTIs. Experimental results demonstrate that iGRLDTI yields better performance that several state-of-the-art computational methods on the benchmark dataset. Besides, our case study indicates that iGRLDTI can successfully identify novel DTIs with more distinguishable features of drugs and targets. AVAILABILITY AND IMPLEMENTATION: Python codes and dataset are available at https://github.com/stevejobws/iGRLDTI/.


Asunto(s)
Descubrimiento de Drogas , Redes Neurales de la Computación , Simulación por Computador , Descubrimiento de Drogas/métodos , Interacciones Farmacológicas
10.
PLoS Comput Biol ; 19(6): e1011207, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37339154

RESUMEN

Interactions between transcription factor and target gene form the main part of gene regulation network in human, which are still complicating factors in biological research. Specifically, for nearly half of those interactions recorded in established database, their interaction types are yet to be confirmed. Although several computational methods exist to predict gene interactions and their type, there is still no method available to predict them solely based on topology information. To this end, we proposed here a graph-based prediction model called KGE-TGI and trained in a multi-task learning manner on a knowledge graph that we specially constructed for this problem. The KGE-TGI model relies on topology information rather than being driven by gene expression data. In this paper, we formulate the task of predicting interaction types of transcript factor and target genes as a multi-label classification problem for link types on a heterogeneous graph, coupled with solving another link prediction problem that is inherently related. We constructed a ground truth dataset as benchmark and evaluated the proposed method on it. As a result of the 5-fold cross experiments, the proposed method achieved average AUC values of 0.9654 and 0.9339 in the tasks of link prediction and link type classification, respectively. In addition, the results of a series of comparison experiments also prove that the introduction of knowledge information significantly benefits to the prediction and that our methodology achieve state-of-the-art performance in this problem.


Asunto(s)
Reconocimiento de Normas Patrones Automatizadas , Factores de Transcripción , Humanos , Bases de Datos Factuales , Factores de Transcripción/genética , Redes Reguladoras de Genes , Proteoma , Algoritmos , Biología de Sistemas , Ontología de Genes
11.
Methods ; 220: 106-114, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37972913

RESUMEN

Discovering new indications for existing drugs is a promising development strategy at various stages of drug research and development. However, most of them complete their tasks by constructing a variety of heterogeneous networks without considering available higher-order connectivity patterns in heterogeneous biological information networks, which are believed to be useful for improving the accuracy of new drug discovering. To this end, we propose a computational-based model, called SFRLDDA, for drug-disease association prediction by using semantic graph and function similarity representation learning. Specifically, SFRLDDA first integrates a heterogeneous information network (HIN) by drug-disease, drug-protein, protein-disease associations, and their biological knowledge. Second, different representation learning strategies are applied to obtain the feature representations of drugs and diseases from different perspectives over semantic graph and function similarity graphs constructed, respectively. At last, a Random Forest classifier is incorporated by SFRLDDA to discover potential drug-disease associations (DDAs). Experimental results demonstrate that SFRLDDA yields a best performance when compared with other state-of-the-art models on three benchmark datasets. Moreover, case studies also indicate that the simultaneous consideration of semantic graph and function similarity of drugs and diseases in the HIN allows SFRLDDA to precisely predict DDAs in a more comprehensive manner.


Asunto(s)
Algoritmos , Semántica , Servicios de Información
12.
BMC Bioinformatics ; 24(1): 451, 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38030973

RESUMEN

BACKGROUND: As an important task in bioinformatics, clustering analysis plays a critical role in understanding the functional mechanisms of many complex biological systems, which can be modeled as biological networks. The purpose of clustering analysis in biological networks is to identify functional modules of interest, but there is a lack of online clustering tools that visualize biological networks and provide in-depth biological analysis for discovered clusters. RESULTS: Here we present BioCAIV, a novel webserver dedicated to maximize its accessibility and applicability on the clustering analysis of biological networks. This, together with its user-friendly interface, assists biological researchers to perform an accurate clustering analysis for biological networks and identify functionally significant modules for further assessment. CONCLUSIONS: BioCAIV is an efficient clustering analysis webserver designed for a variety of biological networks. BioCAIV is freely available without registration requirements at http://bioinformatics.tianshanzw.cn:8888/BioCAIV/ .


Asunto(s)
Biología Computacional , Programas Informáticos , Análisis por Conglomerados
13.
Brief Bioinform ; 22(5)2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-33693513

RESUMEN

Proteins interact with each other to play critical roles in many biological processes in cells. Although promising, laboratory experiments usually suffer from the disadvantages of being time-consuming and labor-intensive. The results obtained are often not robust and considerably uncertain. Due recently to advances in high-throughput technologies, a large amount of proteomics data has been collected and this presents a significant opportunity and also a challenge to develop computational models to predict protein-protein interactions (PPIs) based on these data. In this paper, we present a comprehensive survey of the recent efforts that have been made towards the development of effective computational models for PPI prediction. The survey introduces the algorithms that can be used to learn computational models for predicting PPIs, and it classifies these models into different categories. To understand their relative merits, the paper discusses different validation schemes and metrics to evaluate the prediction performance. Biological databases that are commonly used in different experiments for performance comparison are also described and their use in a series of extensive experiments to compare different prediction models are discussed. Finally, we present some open issues in PPI prediction for future work. We explain how the performance of PPI prediction can be improved if these issues are effectively tackled.


Asunto(s)
Biología Computacional/métodos , Mapeo de Interacción de Proteínas/métodos , Proteínas/metabolismo , Programas Informáticos , Máquina de Vectores de Soporte , Bases de Datos Genéticas , Bases de Datos de Proteínas , Ontología de Genes , Humanos , Modelos Moleculares , Conformación Proteica , Dominios y Motivos de Interacción de Proteínas , Mapeo de Interacción de Proteínas/estadística & datos numéricos , Proteínas/química , Proteínas/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
14.
Nat Mater ; 21(12): 1366-1372, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36302957

RESUMEN

A topological insulator (TI) interfaced with an s-wave superconductor has been predicted to host topological superconductivity. Although the growth of epitaxial TI films on s-wave superconductors has been achieved by molecular-beam epitaxy, it remains an outstanding challenge for synthesizing atomically thin TI/superconductor heterostructures, which are critical for engineering the topological superconducting phase. Here we used molecular-beam epitaxy to grow Bi2Se3 films with a controlled thickness on monolayer NbSe2 and performed in situ angle-resolved photoemission spectroscopy and ex situ magnetotransport measurements on these heterostructures. We found that the emergence of Rashba-type bulk quantum-well bands and spin-non-degenerate surface states coincides with a marked suppression of the in-plane upper critical magnetic field of the superconductivity in Bi2Se3/monolayer NbSe2 heterostructures. This is a signature of a crossover from Ising- to Rashba-type superconducting pairings, induced by altering the Bi2Se3 film thickness. Our work opens a route for exploring a robust topological superconducting phase in TI/Ising superconductor heterostructures.

15.
BMC Bioinformatics ; 23(1): 447, 2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36303135

RESUMEN

BACKGROUND: The site information of substrates that can be cleaved by human immunodeficiency virus 1 proteases (HIV-1 PRs) is of great significance for designing effective inhibitors against HIV-1 viruses. A variety of machine learning-based algorithms have been developed to predict HIV-1 PR cleavage sites by extracting relevant features from substrate sequences. However, only relying on the sequence information is not sufficient to ensure a promising performance due to the uncertainty in the way of separating the datasets used for training and testing. Moreover, the existence of noisy data, i.e., false positive and false negative cleavage sites, could negatively influence the accuracy performance. RESULTS: In this work, an ensemble learning algorithm for predicting HIV-1 PR cleavage sites, namely EM-HIV, is proposed by training a set of weak learners, i.e., biased support vector machine classifiers, with the asymmetric bagging strategy. By doing so, the impact of data imbalance and noisy data can thus be alleviated. Besides, in order to make full use of substrate sequences, the features used by EM-HIV are collected from three different coding schemes, including amino acid identities, chemical properties and variable-length coevolutionary patterns, for the purpose of constructing more relevant feature vectors of octamers. Experiment results on three independent benchmark datasets demonstrate that EM-HIV outperforms state-of-the-art prediction algorithm in terms of several evaluation metrics. Hence, EM-HIV can be regarded as a useful tool to accurately predict HIV-1 PR cleavage sites.


Asunto(s)
Proteasa del VIH , VIH-1 , Algoritmos , Proteasa del VIH/química , VIH-1/enzimología , Aprendizaje Automático , Especificidad por Sustrato
16.
BMC Bioinformatics ; 23(1): 234, 2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-35710342

RESUMEN

BACKGROUND: Protein-protein interaction (PPI) plays an important role in regulating cells and signals. Despite the ongoing efforts of the bioassay group, continued incomplete data limits our ability to understand the molecular roots of human disease. Therefore, it is urgent to develop a computational method to predict PPIs from the perspective of molecular system. METHODS: In this paper, a highly efficient computational model, MTV-PPI, is proposed for PPI prediction based on a heterogeneous molecular network by learning inter-view protein sequences and intra-view interactions between molecules simultaneously. On the one hand, the inter-view feature is extracted from the protein sequence by k-mer method. On the other hand, we use a popular embedding method LINE to encode the heterogeneous molecular network to obtain the intra-view feature. Thus, the protein representation used in MTV-PPI is constructed by the aggregation of its inter-view feature and intra-view feature. Finally, random forest is integrated to predict potential PPIs. RESULTS: To prove the effectiveness of MTV-PPI, we conduct extensive experiments on a collected heterogeneous molecular network with the accuracy of 86.55%, sensitivity of 82.49%, precision of 89.79%, AUC of 0.9301 and AUPR of 0.9308. Further comparison experiments are performed with various protein representations and classifiers to indicate the effectiveness of MTV-PPI in predicting PPIs based on a complex network. CONCLUSION: The achieved experimental results illustrate that MTV-PPI is a promising tool for PPI prediction, which may provide a new perspective for the future interactions prediction researches based on heterogeneous molecular network.


Asunto(s)
Mapeo de Interacción de Proteínas , Proteínas , Secuencia de Aminoácidos , Biología Computacional/métodos , Humanos , Mapeo de Interacción de Proteínas/métodos , Proteínas/metabolismo
17.
BMC Bioinformatics ; 23(1): 516, 2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36456957

RESUMEN

BACKGROUND: Drug repositioning is a very important task that provides critical information for exploring the potential efficacy of drugs. Yet developing computational models that can effectively predict drug-disease associations (DDAs) is still a challenging task. Previous studies suggest that the accuracy of DDA prediction can be improved by integrating different types of biological features. But how to conduct an effective integration remains a challenging problem for accurately discovering new indications for approved drugs. METHODS: In this paper, we propose a novel meta-path based graph representation learning model, namely RLFDDA, to predict potential DDAs on heterogeneous biological networks. RLFDDA first calculates drug-drug similarities and disease-disease similarities as the intrinsic biological features of drugs and diseases. A heterogeneous network is then constructed by integrating DDAs, disease-protein associations and drug-protein associations. With such a network, RLFDDA adopts a meta-path random walk model to learn the latent representations of drugs and diseases, which are concatenated to construct joint representations of drug-disease associations. As the last step, we employ the random forest classifier to predict potential DDAs with their joint representations. RESULTS: To demonstrate the effectiveness of RLFDDA, we have conducted a series of experiments on two benchmark datasets by following a ten-fold cross-validation scheme. The results show that RLFDDA yields the best performance in terms of AUC and F1-score when compared with several state-of-the-art DDAs prediction models. We have also conducted a case study on two common diseases, i.e., paclitaxel and lung tumors, and found that 7 out of top-10 diseases and 8 out of top-10 drugs have already been validated for paclitaxel and lung tumors respectively with literature evidence. Hence, the promising performance of RLFDDA may provide a new perspective for novel DDAs discovery over heterogeneous networks.


Asunto(s)
Aprendizaje , Neoplasias Pulmonares , Humanos , Benchmarking , Descubrimiento de Drogas , Paclitaxel
18.
Bioinformatics ; 37(4): 542-550, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32931549

RESUMEN

MOTIVATION: Clustering analysis in a biological network is to group biological entities into functional modules, thus providing valuable insight into the understanding of complex biological systems. Existing clustering techniques make use of lower-order connectivity patterns at the level of individual biological entities and their connections, but few of them can take into account of higher-order connectivity patterns at the level of small network motifs. RESULTS: Here, we present a novel clustering framework, namely HiSCF, to identify functional modules based on the higher-order structure information available in a biological network. Taking advantage of higher-order Markov stochastic process, HiSCF is able to perform the clustering analysis by exploiting a variety of network motifs. When compared with several state-of-the-art clustering models, HiSCF yields the best performance for two practical clustering applications, i.e. protein complex identification and gene co-expression module detection, in terms of accuracy. The promising performance of HiSCF demonstrates that the consideration of higher-order network motifs gains new insight into the analysis of biological networks, such as the identification of overlapping protein complexes and the inference of new signaling pathways, and also reveals the rich higher-order organizational structures presented in biological networks. AVAILABILITY AND IMPLEMENTATION: HiSCF is available at https://github.com/allenv5/HiSCF. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Algoritmos , Redes Reguladoras de Genes , Análisis por Conglomerados , Expresión Génica , Cadenas de Markov
19.
Phys Rev Lett ; 129(27): 277001, 2022 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-36638298

RESUMEN

In this Letter, we establish a new theoretical paradigm for vortex Majorana physics in the recently discovered topological iron-based superconductors (TFeSCs). While TFeSCs are widely accepted as an exemplar of topological insulators (TIs) with intrinsic s-wave superconductivity, our theory implies that such a common belief could be oversimplified. Our main finding is that the normal-state bulk Dirac nodes, usually ignored in TI-based vortex Majorana theories for TFeSCs, will play a key role of determining the vortex state topology. In particular, the interplay between TI and Dirac nodal bands will lead to multiple competing topological phases for a superconducting vortex line in TFeSCs, including an unprecedented hybrid topological vortex state that carries both Majorana bound states and a gapless dispersion. Remarkably, this exotic hybrid vortex phase generally exists in the vortex phase diagram for our minimal model for TFeSCs and is directly relevant to TFeSC candidates such as LiFeAs. When the fourfold rotation symmetry is broken by vortex-line tilting or curving, the hybrid vortex gets topologically trivialized and becomes Majorana free, which could explain the puzzle of ubiquitous trivial vortices observed in LiFeAs. The origin of the Majorana signal in other TFeSC candidates such as FeTe_{x}Se_{1-x} and CaKFe_{4}As_{4} is also interpreted within our theory framework. Our theory sheds new light on theoretically understanding and experimentally engineering Majorana physics in high-temperature iron-based systems.

20.
Phys Rev Lett ; 127(12): 125901, 2021 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-34597081

RESUMEN

In two-dimensional insulators with time-reversal (TR) symmetry, a nonzero local Berry curvature of low-energy massive Dirac fermions can give rise to nontrivial spin and charge responses, even though the integral of the Berry curvature over all occupied states is zero. In this Letter, we present a new effect induced by the electronic Berry curvature. By studying electron-phonon interactions in BaMnSb_{2}, a prototype two-dimensional Dirac material possessing two TR-related massive Dirac cones, we find that the nonzero local Berry curvature of electrons can induce a phonon angular momentum. The direction of this phonon angular momentum is locked to the phonon propagation direction, and thus we refer to it as "phonon helicity" in a way that is reminiscent of electron helicity in spin-orbit-coupled electronic systems. We discuss possible experimental probes of such phonon helicity.

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