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Noise reduction in protein-protein interaction graphs by the implementation of a novel weighting scheme.

ABSTRACT: BACKGROUND: Recent technological advances applied to biology such as yeast-two-hybrid, phage display and mass spectrometry have enabled us to create a detailed map of protein interaction networks. These interaction networks represent a rich, yet noisy, source of data that could be used to extract meaningful information, such as protein complexes. Several interaction network weighting schemes have been proposed so far in the literature in order to eliminate the noise inherent in interactome data. In this paper, we propose a novel weighting scheme and apply it to the S. cerevisiae interactome. Complex prediction rates are improved by up to 39%, depending on the clustering algorithm applied. RESULTS: We adopt a two step procedure. During the first step, by applying both novel and well established protein-protein interaction (PPI) weighting methods, weights are introduced to the original interactome graph based on the confidence level that a given interaction is a true-positive one. The second step applies clustering using established algorithms in the field of graph theory, as well as two variations of Spectral clustering. The clustered interactome networks are also cross-validated against the confirmed protein complexes present in the MIPS database. CONCLUSIONS: The results of our experimental work demonstrate that interactome graph weighting methods clearly improve the clustering results of several clustering algorithms. Moreover, our proposed weighting scheme outperforms other approaches of PPI graph weighting.

SUBMITTER: Kritikos GD

PROVIDER: S-EPMC3230908 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Noise reduction in protein-protein interaction graphs by the implementation of a novel weighting scheme.

Kritikos George D GD Moschopoulos Charalampos C Vazirgiannis Michalis M Kossida Sophia S

BMC bioinformatics 20110616

<h4>Background</h4>Recent technological advances applied to biology such as yeast-two-hybrid, phage display and mass spectrometry have enabled us to create a detailed map of protein interaction networks. These interaction networks represent a rich, yet noisy, source of data that could be used to extract meaningful information, such as protein complexes. Several interaction network weighting schemes have been proposed so far in the literature in order to eliminate the noise inherent in interactom ...[more]

PMID: 21679454

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Project description:ObjectivesSelectively attending to a target talker while ignoring multiple interferers (competing talkers and background noise) is more difficult for hearing-impaired (HI) individuals compared to normal-hearing (NH) listeners. Such tasks also become more difficult as background noise levels increase. To overcome these difficulties, hearing aids (HAs) offer noise reduction (NR) schemes. The objective of this study was to investigate the effect of NR processing (inactive, where the NR feature was switched off, vs. active, where the NR feature was switched on) on the neural representation of speech envelopes across two different background noise levels [+3 dB signal-to-noise ratio (SNR) and +8 dB SNR] by using a stimulus reconstruction (SR) method.DesignTo explore how NR processing supports the listeners' selective auditory attention, we recruited 22 HI participants fitted with HAs. To investigate the interplay between NR schemes, background noise, and neural representation of the speech envelopes, we used electroencephalography (EEG). The participants were instructed to listen to a target talker in front while ignoring a competing talker in front in the presence of multi-talker background babble noise.ResultsThe results show that the neural representation of the attended speech envelope was enhanced by the active NR scheme for both background noise levels. The neural representation of the attended speech envelope at lower (+3 dB) SNR was shifted, approximately by 5 dB, toward the higher (+8 dB) SNR when the NR scheme was turned on. The neural representation of the ignored speech envelope was modulated by the NR scheme and was mostly enhanced in the conditions with more background noise. The neural representation of the background noise was modulated (i.e., reduced) by the NR scheme and was significantly reduced in the conditions with more background noise. The neural representation of the net sum of the ignored acoustic scene (ignored talker and background babble) was not modulated by the NR scheme but was significantly reduced in the conditions with a reduced level of background noise. Taken together, we showed that the active NR scheme enhanced the neural representation of both the attended and the ignored speakers and reduced the neural representation of background noise, while the net sum of the ignored acoustic scene was not enhanced.ConclusionAltogether our results support the hypothesis that the NR schemes in HAs serve to enhance the neural representation of speech and reduce the neural representation of background noise during a selective attention task. We contend that these results provide a neural index that could be useful for assessing the effects of HAs on auditory and cognitive processing in HI populations.

Project description:Protein design algorithms enumerate a combinatorial number of candidate structures to compute the Global Minimum Energy Conformation (GMEC). To efficiently find the GMEC, protein design algorithms must methodically reduce the conformational search space. By applying distance and energy cutoffs, the protein system to be designed can thus be represented using a sparse residue interaction graph, where the number of interacting residue pairs is less than all pairs of mutable residues, and the corresponding GMEC is called the sparse GMEC. However, ignoring some pairwise residue interactions can lead to a change in the energy, conformation, or sequence of the sparse GMEC vs. the original or the full GMEC. Despite the widespread use of sparse residue interaction graphs in protein design, the above mentioned effects of their use have not been previously analyzed. To analyze the costs and benefits of designing with sparse residue interaction graphs, we computed the GMECs for 136 different protein design problems both with and without distance and energy cutoffs, and compared their energies, conformations, and sequences. Our analysis shows that the differences between the GMECs depend critically on whether or not the design includes core, boundary, or surface residues. Moreover, neglecting long-range interactions can alter local interactions and introduce large sequence differences, both of which can result in significant structural and functional changes. Designs on proteins with experimentally measured thermostability show it is beneficial to compute both the full and the sparse GMEC accurately and efficiently. To this end, we show that a provable, ensemble-based algorithm can efficiently compute both GMECs by enumerating a small number of conformations, usually fewer than 1000. This provides a novel way to combine sparse residue interaction graphs with provable, ensemble-based algorithms to reap the benefits of sparse residue interaction graphs while avoiding their potential inaccuracies.

Dataset Information

Noise reduction in protein-protein interaction graphs by the implementation of a novel weighting scheme.

Publications

Noise reduction in protein-protein interaction graphs by the implementation of a novel weighting scheme.

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