BackgroundRecently, high-throughput experimental techniques have generated a large amount of protein-protein interaction (PPI) data which can construct large complex PPI networks for numerous organisms. System biology attempts to understand cellular organization and function by analyzing these PPI networks. However, most studies still focus on static PPI networks which neglect the dynamic information of PPI.ResultsThe gene expression data under different time points and conditions can reveal the dynamic information of proteins. In this study, we used an active probability-based method to distinguish the active level of proteins at different active time points. We constructed dynamic probabilistic protein networks (DPPN) to integrate dynamic information of protein into static PPI networks. Based on DPPN, we subsequently proposed a novel method to identify protein complexes, which could effectively exploit topological structure as well as dynamic information of DPPN. We used three different yeast PPI datasets and gene expression data to construct three DPPNs. When applied to three DPPNs, many well-characterized protein complexes were accurately identified by this method.ConclusionThe shift from static PPI networks to dynamic PPI networks is essential to accurately identify protein complex. This method not only can be applied to identify protein complex, but also establish a framework to integrate dynamic information into static networks for other applications, such as pathway analysis.

BackgroundNext-generation sequencing has been used by investigators to address a diverse range of biological problems through, for example, polymorphism and mutation discovery and microRNA profiling. However, compared to conventional sequencing, the error rates for next-generation sequencing are often higher, which impacts the downstream genomic analysis. Recently, Wang et al. (BMC Bioinformatics 13:185, 2012) proposed a shadow regression approach to estimate the error rates for next-generation sequencing data based on the assumption of a linear relationship between the number of reads sequenced and the number of reads containing errors (denoted as shadows). However, this linear read-shadow relationship may not be appropriate for all types of sequence data. Therefore, it is necessary to estimate the error rates in a more reliable way without assuming linearity. We proposed an empirical error rate estimation approach that employs cubic and robust smoothing splines to model the relationship between the number of reads sequenced and the number of shadows.ResultsWe performed simulation studies using a frequency-based approach to generate the read and shadow counts directly, which can mimic the real sequence counts data structure. Using simulation, we investigated the performance of the proposed approach and compared it to that of shadow linear regression. The proposed approach provided more accurate error rate estimations than the shadow linear regression approach for all the scenarios tested. We also applied the proposed approach to assess the error rates for the sequence data from the MicroArray Quality Control project, a mutation screening study, the Encyclopedia of DNA Elements project, and bacteriophage PhiX DNA samples.ConclusionsThe proposed empirical error rate estimation approach does not assume a linear relationship between the error-free read and shadow counts and provides more accurate estimations of error rates for next-generation, short-read sequencing data.

BackgroundAccurate determination of protein complexes has become a key task of system biology for revealing cellular organization and function. Up to now, the protein complex prediction methods are mostly focused on static protein protein interaction (PPI) networks. However, cellular systems are highly dynamic and responsive to cues from the environment. The shift from static PPI networks to dynamic PPI networks is essential to accurately predict protein complex.ResultsThe gene expression data contains crucial dynamic information of proteins and PPIs, along with high-throughput experimental PPI data, are valuable for protein complex prediction. Firstly, we exploit gene expression data to calculate the active time point and the active probability of each protein and PPI. The dynamic active information is integrated into high-throughput PPI data to construct dynamic PPI networks. Secondly, a novel method for predicting protein complexes from the dynamic PPI networks is proposed based on core-attachment structural feature. Our method can effectively exploit not only the dynamic active information but also the topology structure information based on the dynamic PPI networks.ConclusionsWe construct four dynamic PPI networks, and accurately predict many well-characterized protein complexes. The experimental results show that (i) the dynamic active information significantly improves the performance of protein complex prediction; (ii) our method can effectively make good use of both the dynamic active information and the topology structure information of dynamic PPI networks to achieve state-of-the-art protein complex prediction capabilities.

BackgroundNext-generation sequencing has been used by investigators to address a diverse range of biological problems through, for example, polymorphism and mutation discovery and microRNA profiling. However, compared to conventional sequencing, the error rates for next-generation sequencing are often higher, which impacts the downstream genomic analysis. Recently, Wang et al. (BMC Bioinformatics 13:185, 2012) proposed a shadow regression approach to estimate the error rates for next-generation sequencing data based on the assumption of a linear relationship between the number of reads sequenced and the number of reads containing errors (denoted as shadows). However, this linear read-shadow relationship may not be appropriate for all types of sequence data. Therefore, it is necessary to estimate the error rates in a more reliable way without assuming linearity. We proposed an empirical error rate estimation approach that employs cubic and robust smoothing splines to model the relationship between the number of reads sequenced and the number of shadows.ResultsWe performed simulation studies using a frequency-based approach to generate the read and shadow counts directly, which can mimic the real sequence counts data structure. Using simulation, we investigated the performance of the proposed approach and compared it to that of shadow linear regression. The proposed approach provided more accurate error rate estimations than the shadow linear regression approach for all the scenarios tested. We also applied the proposed approach to assess the error rates for the sequence data from the MicroArray Quality Control project, a mutation screening study, the Encyclopedia of DNA Elements project, and bacteriophage PhiX DNA samples.ConclusionsThe proposed empirical error rate estimation approach does not assume a linear relationship between the error-free read and shadow counts and provides more accurate estimations of error rates for next-generation, short-read sequencing data.

BackgroundRecently, high-throughput experimental techniques have generated a large amount of protein-protein interaction (PPI) data which can construct large complex PPI networks for numerous organisms. System biology attempts to understand cellular organization and function by analyzing these PPI networks. However, most studies still focus on static PPI networks which neglect the dynamic information of PPI.ResultsThe gene expression data under different time points and conditions can reveal the dynamic information of proteins. In this study, we used an active probability-based method to distinguish the active level of proteins at different active time points. We constructed dynamic probabilistic protein networks (DPPN) to integrate dynamic information of protein into static PPI networks. Based on DPPN, we subsequently proposed a novel method to identify protein complexes, which could effectively exploit topological structure as well as dynamic information of DPPN. We used three different yeast PPI datasets and gene expression data to construct three DPPNs. When applied to three DPPNs, many well-characterized protein complexes were accurately identified by this method.ConclusionThe shift from static PPI networks to dynamic PPI networks is essential to accurately identify protein complex. This method not only can be applied to identify protein complex, but also establish a framework to integrate dynamic information into static networks for other applications, such as pathway analysis.

BackgroundAccurate determination of protein complexes has become a key task of system biology for revealing cellular organization and function. Up to now, the protein complex prediction methods are mostly focused on static protein protein interaction (PPI) networks. However, cellular systems are highly dynamic and responsive to cues from the environment. The shift from static PPI networks to dynamic PPI networks is essential to accurately predict protein complex.ResultsThe gene expression data contains crucial dynamic information of proteins and PPIs, along with high-throughput experimental PPI data, are valuable for protein complex prediction. Firstly, we exploit gene expression data to calculate the active time point and the active probability of each protein and PPI. The dynamic active information is integrated into high-throughput PPI data to construct dynamic PPI networks. Secondly, a novel method for predicting protein complexes from the dynamic PPI networks is proposed based on core-attachment structural feature. Our method can effectively exploit not only the dynamic active information but also the topology structure information based on the dynamic PPI networks.ConclusionsWe construct four dynamic PPI networks, and accurately predict many well-characterized protein complexes. The experimental results show that (i) the dynamic active information significantly improves the performance of protein complex prediction; (ii) our method can effectively make good use of both the dynamic active information and the topology structure information of dynamic PPI networks to achieve state-of-the-art protein complex prediction capabilities.