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1.

Background:

We participated in three of the protein-protein interaction subtasks of the Second BioCreative Challenge: classification of abstracts relevant for protein-protein interaction (interaction article subtask [IAS]), discovery of protein pairs (interaction pair subtask [IPS]), and identification of text passages characterizing protein interaction (interaction sentences subtask [ISS]) in full-text documents. We approached the abstract classification task with a novel, lightweight linear model inspired by spam detection techniques, as well as an uncertainty-based integration scheme. We also used a support vector machine and singular value decomposition on the same features for comparison purposes. Our approach to the full-text subtasks (protein pair and passage identification) includes a feature expansion method based on word proximity networks.

Results:

Our approach to the abstract classification task (IAS) was among the top submissions for this task in terms of measures of performance used in the challenge evaluation (accuracy, F-score, and area under the receiver operating characteristic curve). We also report on a web tool that we produced using our approach: the Protein Interaction Abstract Relevance Evaluator (PIARE). Our approach to the full-text tasks resulted in one of the highest recall rates as well as mean reciprocal rank of correct passages.

Conclusion:

Our approach to abstract classification shows that a simple linear model, using relatively few features, can generalize and uncover the conceptual nature of protein-protein interactions from the bibliome. Because the novel approach is based on a rather lightweight linear model, it can easily be ported and applied to similar problems. In full-text problems, the expansion of word features with word proximity networks is shown to be useful, although the need for some improvements is discussed.
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2.

Background:

The goal of text mining is to make the information conveyed in scientific publications accessible to structured search and automatic analysis. Two important subtasks of text mining are entity mention normalization - to identify biomedical objects in text - and extraction of qualified relationships between those objects. We describe a method for identifying genes and relationships between proteins.

Results:

We present solutions to gene mention normalization and extraction of protein-protein interactions. For the first task, we identify genes by using background knowledge on each gene, namely annotations related to function, location, disease, and so on. Our approach currently achieves an f-measure of 86.4% on the BioCreative II gene normalization data. For the extraction of protein-protein interactions, we pursue an approach that builds on classical sequence analysis: motifs derived from multiple sequence alignments. The method achieves an f-measure of 24.4% (micro-average) in the BioCreative II interaction pair subtask.

Conclusion:

For gene mention normalization, our approach outperforms strategies that utilize only the matching of genes names against dictionaries, without invoking further knowledge on each gene. Motifs derived from alignments of sentences are successful at identifying protein interactions in text; the approach we present in this report is fully automated and performs similarly to systems that require human intervention at one or more stages.

Availability:

Our methods for gene, protein, and species identification, and extraction of protein-protein are available as part of the BioCreative Meta Services (BCMS), see http://bcms.bioinfo.cnio.es/.
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3.

Background:

Research scientists and companies working in the domains of biomedicine and genomics are increasingly faced with the problem of efficiently locating, within the vast body of published scientific findings, the critical pieces of information that are needed to direct current and future research investment.

Results:

In this report we describe approaches taken within the scope of the second BioCreative competition in order to solve two aspects of this problem: detection of novel protein interactions reported in scientific articles, and detection of the experimental method that was used to confirm the interaction. Our approach to the former problem is based on a high-recall protein annotation step, followed by two strict disambiguation steps. The remaining proteins are then combined according to a number of lexico-syntactic filters, which deliver high-precision results while maintaining reasonable recall. The detection of the experimental methods is tackled by a pattern matching approach, which has delivered the best results in the official BioCreative evaluation.

Conclusion:

Although the results of BioCreative clearly show that no tool is sufficiently reliable for fully automated annotations, a few of the proposed approaches (including our own) already perform at a competitive level. This makes them interesting either as standalone tools for preliminary document inspection, or as modules within an environment aimed at supporting the process of curation of biomedical literature.
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4.

Background:

The tasks in BioCreative II were designed to approximate some of the laborious work involved in curating biomedical research papers. The approach to these tasks taken by the University of Edinburgh team was to adapt and extend the existing natural language processing (NLP) system that we have developed as part of a commercial curation assistant. Although this paper concentrates on using NLP to assist with curation, the system can be equally employed to extract types of information from the literature that is immediately relevant to biologists in general.

Results:

Our system was among the highest performing on the interaction subtasks, and competitive performance on the gene mention task was achieved with minimal development effort. For the gene normalization task, a string matching technique that can be quickly applied to new domains was shown to perform close to average.

Conclusion:

The technologies being developed were shown to be readily adapted to the BioCreative II tasks. Although high performance may be obtained on individual tasks such as gene mention recognition and normalization, and document classification, tasks in which a number of components must be combined, such as detection and normalization of interacting protein pairs, are still challenging for NLP systems.
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5.

Background

In the absence of consolidated pipelines to archive biological data electronically, information dispersed in the literature must be captured by manual annotation. Unfortunately, manual annotation is time consuming and the coverage of published interaction data is therefore far from complete. The use of text-mining tools to identify relevant publications and to assist in the initial information extraction could help to improve the efficiency of the curation process and, as a consequence, the database coverage of data available in the literature. The 2006 BioCreative competition was aimed at evaluating text-mining procedures in comparison with manual annotation of protein-protein interactions.

Results

To aid the BioCreative protein-protein interaction task, IntAct and MINT (Molecular INTeraction) provided both the training and the test datasets. Data from both databases are comparable because they were curated according to the same standards. During the manual curation process, the major cause of data loss in mining the articles for information was ambiguity in the mapping of the gene names to stable UniProtKB database identifiers. It was also observed that most of the information about interactions was contained only within the full-text of the publication; hence, text mining of protein-protein interaction data will require the analysis of the full-text of the articles and cannot be restricted to the abstract.

Conclusion

The development of text-mining tools to extract protein-protein interaction information may increase the literature coverage achieved by manual curation. To support the text-mining community, databases will highlight those sentences within the articles that describe the interactions. These will supply data-miners with a high quality dataset for algorithm development. Furthermore, the dictionary of terms created by the BioCreative competitors could enrich the synonym list of the PSI-MI (Proteomics Standards Initiative-Molecular Interactions) controlled vocabulary, which is used by both databases to annotate their data content.
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6.
Wang J  Xie D  Lin H  Yang Z  Zhang Y 《Proteome science》2012,10(Z1):S18

Background

Many biological processes recognize in particular the importance of protein complexes, and various computational approaches have been developed to identify complexes from protein-protein interaction (PPI) networks. However, high false-positive rate of PPIs leads to challenging identification.

Results

A protein semantic similarity measure is proposed in this study, based on the ontology structure of Gene Ontology (GO) terms and GO annotations to estimate the reliability of interactions in PPI networks. Interaction pairs with low GO semantic similarity are removed from the network as unreliable interactions. Then, a cluster-expanding algorithm is used to detect complexes with core-attachment structure on filtered network. Our method is applied to three different yeast PPI networks. The effectiveness of our method is examined on two benchmark complex datasets. Experimental results show that our method performed better than other state-of-the-art approaches in most evaluation metrics.

Conclusions

The method detects protein complexes from large scale PPI networks by filtering GO semantic similarity. Removing interactions with low GO similarity significantly improves the performance of complex identification. The expanding strategy is also effective to identify attachment proteins of complexes.
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7.
Ou-Yang  Le  Yan  Hong  Zhang  Xiao-Fei 《BMC bioinformatics》2017,18(13):463-34

Background

The accurate identification of protein complexes is important for the understanding of cellular organization. Up to now, computational methods for protein complex detection are mostly focus on mining clusters from protein-protein interaction (PPI) networks. However, PPI data collected by high-throughput experimental techniques are known to be quite noisy. It is hard to achieve reliable prediction results by simply applying computational methods on PPI data. Behind protein interactions, there are protein domains that interact with each other. Therefore, based on domain-protein associations, the joint analysis of PPIs and domain-domain interactions (DDI) has the potential to obtain better performance in protein complex detection. As traditional computational methods are designed to detect protein complexes from a single PPI network, it is necessary to design a new algorithm that could effectively utilize the information inherent in multiple heterogeneous networks.

Results

In this paper, we introduce a novel multi-network clustering algorithm to detect protein complexes from multiple heterogeneous networks. Unlike existing protein complex identification algorithms that focus on the analysis of a single PPI network, our model can jointly exploit the information inherent in PPI and DDI data to achieve more reliable prediction results. Extensive experiment results on real-world data sets demonstrate that our method can predict protein complexes more accurately than other state-of-the-art protein complex identification algorithms.

Conclusions

In this work, we demonstrate that the joint analysis of PPI network and DDI network can help to improve the accuracy of protein complex detection.
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8.

Background:

Genome sciences have experienced an increasing demand for efficient text-processing tools that can extract biologically relevant information from the growing amount of published literature. In response, a range of text-mining and information-extraction tools have recently been developed specifically for the biological domain. Such tools are only useful if they are designed to meet real-life tasks and if their performance can be estimated and compared. The BioCreative challenge (Critical Assessment of Information Extraction in Biology) consists of a collaborative initiative to provide a common evaluation framework for monitoring and assessing the state-of-the-art of text-mining systems applied to biologically relevant problems.

Results:

The Second BioCreative assessment (2006 to 2007) attracted 44 teams from 13 countries worldwide, with the aim of evaluating current information-extraction/text-mining technologies developed for one or more of the three tasks defined for this challenge evaluation. These tasks included the recognition of gene mentions in abstracts (gene mention task); the extraction of a list of unique identifiers for human genes mentioned in abstracts (gene normalization task); and finally the extraction of physical protein-protein interaction annotation-relevant information (protein-protein interaction task). The 'gold standard' data used for evaluating submissions for the third task was provided by the interaction databases MINT (Molecular Interaction Database) and IntAct.

Conclusion:

The Second BioCreative assessment almost doubled the number of participants for each individual task when compared with the first BioCreative assessment. An overall improvement in terms of balanced precision and recall was observed for the best submissions for the gene mention (F score 0.87); for the gene normalization task, the best results were comparable (F score 0.81) compared with results obtained for similar tasks posed at the first BioCreative challenge. In case of the protein-protein interaction task, the importance and difficulties of experimentally confirmed annotation extraction from full-text articles were explored, yielding different results depending on the step of the annotation extraction workflow. A common characteristic observed in all three tasks was that the combination of system outputs could yield better results than any single system. Finally, the development of the first text-mining meta-server was promoted within the context of this community challenge.
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9.

Background

Protein complexes play an important role in biological processes. Recent developments in experiments have resulted in the publication of many high-quality, large-scale protein-protein interaction (PPI) datasets, which provide abundant data for computational approaches to the prediction of protein complexes. However, the precision of protein complex prediction still needs to be improved due to the incompletion and noise in PPI networks.

Results

There exist complex and diverse relationships among proteins after integrating multiple sources of biological information. Considering that the influences of different types of interactions are not the same weight for protein complex prediction, we construct a multi-relationship protein interaction network (MPIN) by integrating PPI network topology with gene ontology annotation information. Then, we design a novel algorithm named MINE (identifying protein complexes based on Multi-relationship protein Interaction NEtwork) to predict protein complexes with high cohesion and low coupling from MPIN.

Conclusions

The experiments on yeast data show that MINE outperforms the current methods in terms of both accuracy and statistical significance.
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10.

Background:

Deciphering physical protein-protein interactions is fundamental to elucidating both the functions of proteins and biological processes. The development of high-throughput experimental technologies such as the yeast two-hybrid screening has produced an explosion in data relating to interactions. Since manual curation is intensive in terms of time and cost, there is an urgent need for text-mining tools to facilitate the extraction of such information. The BioCreative (Critical Assessment of Information Extraction systems in Biology) challenge evaluation provided common standards and shared evaluation criteria to enable comparisons among different approaches.

Results:

During the benchmark evaluation of BioCreative 2006, all of our results ranked in the top three places. In the task of filtering articles irrelevant to physical protein interactions, our method contributes a precision of 75.07%, a recall of 81.07%, and an AUC (area under the receiver operating characteristic curve) of 0.847. In the task of identifying protein mentions and normalizing mentions to molecule identifiers, our method is competitive among runs submitted, with a precision of 34.83%, a recall of 24.10%, and an F1 score of28.5%. In extracting protein interaction pairs, our profile-based method was competitive on the SwissProt-only subset (precision = 36.95%, recall = 32.68%, and F1 score = 30.40%) and on the entire dataset (30.96%, 29.35%, and26.20%, respectively). From the biologist's point of view, however, these findings are far from satisfactory. The error analysis presented in this report provides insight into how performance could be improved: three-quarters of false negatives were due to protein normalization problems (532/698), and about one-quarter were due to problems with correctly extracting interactions for this system.

Conclusion:

We present a text-mining framework to extract physical protein-protein interactions from the literature. Three key issues are addressed, namely filtering irrelevant articles, identifying protein names and normalizing them to molecule identifiers, and extracting protein-protein interactions. Our system is among the top three performers in the benchmark evaluation of BioCreative 2006. The tool will be helpful for manual interaction curation and can greatly facilitate the process of extracting protein-protein interactions.
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11.

Background:

Reliable information extraction applications have been a long sought goal of the biomedical text mining community, a goal that if reached would provide valuable tools to benchside biologists in their increasingly difficult task of assimilating the knowledge contained in the biomedical literature. We present an integrated approach to concept recognition in biomedical text. Concept recognition provides key information that has been largely missing from previous biomedical information extraction efforts, namely direct links to well defined knowledge resources that explicitly cement the concept's semantics. The BioCreative II tasks discussed in this special issue have provided a unique opportunity to demonstrate the effectiveness of concept recognition in the field of biomedical language processing.

Results:

Through the modular construction of a protein interaction relation extraction system, we present several use cases of concept recognition in biomedical text, and relate these use cases to potential uses by the benchside biologist.

Conclusion:

Current information extraction technologies are approaching performance standards at which concept recognition can begin to deliver high quality data to the benchside biologist. Our system is available as part of the BioCreative Meta-Server project and on the internet http://bionlp.sourceforge.net.
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12.
Kim Y  Min B  Yi GS 《Proteome science》2012,10(Z1):S9

Background

Deciphering protein-protein interaction (PPI) in domain level enriches valuable information about binding mechanism and functional role of interacting proteins. The 3D structures of complex proteins are reliable source of domain-domain interaction (DDI) but the number of proven structures is very limited. Several resources for the computationally predicted DDI have been generated but they are scattered in various places and their prediction show erratic performances. A well-organized PPI and DDI analysis system integrating these data with fair scoring system is necessary.

Method

We integrated three structure-based DDI datasets and twenty computationally predicted DDI datasets and constructed an interaction analysis system, named IDDI, which enables to browse protein and domain interactions with their relationships. To integrate heterogeneous DDI information, a novel scoring scheme is introduced to determine the reliability of DDI by considering the prediction scores of each DDI and the confidence levels of each prediction method in the datasets, and independencies between predicted datasets. In addition, we connected this DDI information to the comprehensive PPI information and developed a unified interface for the interaction analysis exploring interaction networks at both protein and domain level.

Result

IDDI provides 204,705 DDIs among total 7,351 Pfam domains in the current version. The result presents that total number of DDIs is increased eight times more than that of previous studies. Due to the increment of data, 50.4% of PPIs could be correlated with DDIs which is more than twice of previous resources. Newly designed scoring scheme outperformed the previous system in its accuracy too. User interface of IDDI system provides interactive investigation of proteins and domains in interactions with interconnected way. A specific example is presented to show the efficiency of the systems to acquire the comprehensive information of target protein with PPI and DDI relationships. IDDI is freely available at http://pcode.kaist.ac.kr/iddi/.
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13.

Background

Protein kinase C ζ (PKCζ), an isoform of the atypical protein kinase C, is a pivotal regulator in cancer. However, the molecular and cellular mechanisms whereby PKCζ regulates tumorigenesis and metastasis are still not fully understood. In this study, proteomics and bioinformatics analyses were performed to establish a protein-protein interaction (PPI) network associated with PKCζ, laying a stepping stone to further understand the diverse biological roles of PKCζ.

Methods

Protein complexes associated with PKCζ were purified by co-immunoprecipitation from breast cancer cell MDA-MB-231 and identified by LC-MS/MS. Two biological replicates and two technical replicates were analyzed. The observed proteins were filtered using the CRAPome database to eliminate the potential false positives. The proteomics identification results were combined with PPI database search to construct the interactome network. Gene ontology (GO) and pathway analysis were performed by PANTHER database and DAVID. Next, the interaction between PKCζ and protein phosphatase 2 catalytic subunit alpha (PPP2CA) was validated by co-immunoprecipitation, Western blotting and immunofluorescence. Furthermore, the TCGA database and the COSMIC database were used to analyze the expressions of these two proteins in clinical samples.

Results

The PKCζ centered PPI network containing 178 nodes and 1225 connections was built. Network analysis showed that the identified proteins were significantly associated with several key signaling pathways regulating cancer related cellular processes.

Conclusions

Through combining the proteomics and bioinformatics analyses, a PKCζ centered PPI network was constructed, providing a more complete picture regarding the biological roles of PKCζ in both cancer regulation and other aspects of cellular biology.
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14.
15.
16.

Background

Accurate annotation of protein functions is still a big challenge for understanding life in the post-genomic era. Many computational methods based on protein-protein interaction (PPI) networks have been proposed to predict the function of proteins. However, the precision of these predictions still needs to be improved, due to the incompletion and noise in PPI networks. Integrating network topology and biological information could improve the accuracy of protein function prediction and may also lead to the discovery of multiple interaction types between proteins. Current algorithms generate a single network, which is archived using a weighted sum of all types of protein interactions.

Method

The influences of different types of interactions on the prediction of protein functions are not the same. To address this, we construct multilayer protein networks (MPN) by integrating PPI networks, the domain of proteins, and information on protein complexes. In the MPN, there is more than one type of connections between pairwise proteins. Different types of connections reflect different roles and importance in protein function prediction. Based on the MPN, we propose a new protein function prediction method, named function prediction based on multilayer protein networks (FP-MPN). Given an un-annotated protein, the FP-MPN method visits each layer of the MPN in turn and generates a set of candidate neighbors with known functions. A set of predicted functions for the testing protein is then formed and all of these functions are scored and sorted. Each layer plays different importance on the prediction of protein functions. A number of top-ranking functions are selected to annotate the unknown protein.

Conclusions

The method proposed in this paper was a better predictor when used on Saccharomyces cerevisiae protein data than other function prediction methods previously used. The proposed FP-MPN method takes different roles of connections in protein function prediction into account to reduce the artificial noise by introducing biological information.
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17.
18.

Background

With ever increasing amount of available data on biological networks, modeling and understanding the structure of these large networks is an important problem with profound biological implications. Cellular functions and biochemical events are coordinately carried out by groups of proteins interacting each other in biological modules. Identifying of such modules in protein interaction networks is very important for understanding the structure and function of these fundamental cellular networks. Therefore, developing an effective computational method to uncover biological modules should be highly challenging and indispensable.

Results

The purpose of this study is to introduce a new quantitative measure modularity density into the field of biomolecular networks and develop new algorithms for detecting functional modules in protein-protein interaction (PPI) networks. Specifically, we adopt the simulated annealing (SA) to maximize the modularity density and evaluate its efficiency on simulated networks. In order to address the computational complexity of SA procedure, we devise a spectral method for optimizing the index and apply it to a yeast PPI network.

Conclusions

Our analysis of detected modules by the present method suggests that most of these modules have well biological significance in context of protein complexes. Comparison with the MCL and the modularity based methods shows the efficiency of our method.
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19.

Background

Protein-protein interaction (PPI) plays a core role in cellular functions. Massively parallel supercomputing systems have been actively developed over the past few years, which enable large-scale biological problems to be solved, such as PPI network prediction based on tertiary structures.

Results

We have developed a high throughput and ultra-fast PPI prediction system based on rigid docking, “MEGADOCK”, by employing a hybrid parallelization (MPI/OpenMP) technique assuming usages on massively parallel supercomputing systems. MEGADOCK displays significantly faster processing speed in the rigid-body docking process that leads to full utilization of protein tertiary structural data for large-scale and network-level problems in systems biology. Moreover, the system was scalable as shown by measurements carried out on two supercomputing environments. We then conducted prediction of biological PPI networks using the post-docking analysis.

Conclusions

We present a new protein-protein docking engine aimed at exhaustive docking of mega-order numbers of protein pairs. The system was shown to be scalable by running on thousands of nodes. The software package is available at: http://www.bi.cs.titech.ac.jp/megadock/k/.
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20.

Background

Tandem affinity purification coupled with mass-spectrometry (TAP/MS) analysis is a popular method for the identification of novel endogenous protein-protein interactions (PPIs) in large-scale. Computational analysis of TAP/MS data is a critical step, particularly for high-throughput datasets, yet it remains challenging due to the noisy nature of TAP/MS data.

Results

We investigated several major TAP/MS data analysis methods for identifying PPIs, and developed an advanced method, which incorporates an improved statistical method to filter out false positives from the negative controls. Our method is named PPIRank that stands for PPI rank ing in TAP/MS data. We compared PPIRank with several other existing methods in analyzing two pathway-specific TAP/MS PPI datasets from Drosophila.

Conclusion

Experimental results show that PPIRank is more capable than other approaches in terms of identifying known interactions collected in the BioGRID PPI database. Specifically, PPIRank is able to capture more true interactions and simultaneously less false positives in both Insulin and Hippo pathways of Drosophila Melanogaster.
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