Dataset Information

Interspecies data mining to predict novel ING-protein interactions in human.

ABSTRACT: BACKGROUND:The INhibitor of Growth (ING) family of type II tumor suppressors (ING1-ING5) is involved in many cellular processes such as cell aging, apoptosis, DNA repair and tumorigenesis. To expand our understanding of the proteins with which the ING proteins interact, we designed a method that did not depend upon large-scale proteomics-based methods, since they may fail to highlight transient or relatively weak interactions. Here we test a cross-species (yeast, fly, and human) bioinformatics-based approach to identify potential human ING-interacting proteins with higher probability and accuracy than approaches based on screens in a single species. RESULTS:We confirm the validity of this screen and show that ING1 interacts specifically with three of the three proteins tested; p38MAPK, MEKK4 and RAD50. These novel ING-interacting proteins further link ING proteins to cell stress and DNA damage signaling, providing previously unknown upstream links to DNA damage response pathways in which ING1 participates. The bioinformatics approach we describe can be used to create an interaction prediction list for any human proteins with yeast homolog(s). CONCLUSION:None of the validated interactions were predicted by the conventional protein-protein interaction tools we tested. Validation of our approach by traditional laboratory techniques shows that we can extract value from the voluminous weak interaction data already elucidated in yeast and fly databases. We therefore propose that the weak (low signal to noise ratio) data from large-scale interaction datasets are currently underutilized.

SUBMITTER: Gordon PM

PROVIDER: S-EPMC2565686 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interspecies data mining to predict novel ING-protein interactions in human.

Gordon Paul M K PM Soliman Mohamed A MA Bose Pinaki P Trinh Quang Q Sensen Christoph W CW Riabowol Karl K

BMC genomics 20080918

<h4>Background</h4>The INhibitor of Growth (ING) family of type II tumor suppressors (ING1-ING5) is involved in many cellular processes such as cell aging, apoptosis, DNA repair and tumorigenesis. To expand our understanding of the proteins with which the ING proteins interact, we designed a method that did not depend upon large-scale proteomics-based methods, since they may fail to highlight transient or relatively weak interactions. Here we test a cross-species (yeast, fly, and human) bioinfor ...[more]

PMID: 18801192

Similar Datasets

Project description:PurposeLower dose outside the planned treatment area in lung stereotactic radiotherapy has been linked to increased risk of distant metastasis (DM) possibly due to underdosage of microscopic disease (MDE). Independently, tumour density on pretreatment computed tomography (CT) has been linked to risk of MDE. No studies have investigated the interaction between imaging biomarkers and incidental dose. The interaction would showcase whether the impact of dose on outcome is dependent on imaging and, hence, if imaging could inform which patients require dose escalation outside the gross tumour volume (GTV). We propose an image-based data mining methodology to investigate density-dose interactions radially from the GTV to predict DM with no a priori assumption on location.MethodsDose and density were quantified in 1-mm annuli around the GTV for 199 patients with early-stage lung cancer treated with 60 Gy in 5 fractions. Each annulus was summarised by three density and three dose parameters. For parameter combinations, Cox regressions were performed including a dose-density interaction in independent annuli. Heatmaps were created that described improvement in DM prediction due to the interaction. Regions of significant improvement were identified and studied in overall outcome models.ResultsDose-density interactions were identified that significantly improved prediction for over 50% of bootstrap resamples. Dose and density parameters were not significant when the interaction was omitted. Tumour density variance and high peritumour density were associated with DM for patients with more cold spots (less than 30-Gy EQD2) and non-uniform dose about 3 cm outside of the GTV. Associations identified were independent of the mean GTV dose.ConclusionsPatients with high tumour variance and peritumour density have increased risk of DM if there is a low and non-uniform dose outside the GTV. The dose regions are independent of tumour dose, suggesting that incidental dose may play an important role in controlling occult disease. Understanding such interactions is key to identifying patients who will benefit from dose-escalation. The methodology presented allowed spatial dose-density interactions to be studied at the exploratory stage for the first time. This could accelerate the clinical implementation of imaging biomarkers by demonstrating the impact of incidental dose for tumours of varying characteristics in routine data.

Project description:Infection by the human blood fluke, Schistosoma mansoni involves a variety of cross-species protein- protein interactions. The pathogen expresses a diverse arsenal of proteins that facilitate the breach of physical and biochemical barriers present in skin evasion of the immune system, and digestion of human plasma proteins including albumin and hemoglobin, allowing schistosomes to reside in the host for years. However, only a small number of specific interactions between S. mansoni and human proteins have been identified. We present and apply a protocol that generates testable predictions of S. mansoni-human protein interactions. In this study, we have preliminary predictions of novel interactions between schistosome and human proteins relevant to infection and the ability of the parasite to evade the immune system. We applied a computational whole-genome comparative approach to predict potential S. mansoni-human protein interactions based on similarity to known protein complexes. We first predict S. mansoni -human protein interactions based on similarity to known protein complexes. Putative interactions were then scored and assessed using several contextual filters, including the use of annotation automatically derived from literature using a simple natural language processing methodology. Next, in vitro experiments were carried out between schistosome and host proteins to validate several prospective predictions. Our method predicted 7 out of the 10 previously known cross-species interactions involved in pathogenesis between S. mansoni and its human host. Interestingly, two novel putative interactions involving Schistosoma proteins, the cercarial elastase SmCE, and the adult tegument surface protein Sm29, were also predicted and experimentally characterized. Preliminary data suggest that elafin, a host endogenous serine protease inhibitor, may be a novel substrate for SmCE. Additionally, CD59, an inhibitor of the membrane attack complex, could interact with Sm29. Furthermore, the application framework provides an integrated methodology for investigation of host-pathogen interactions and an extensive source of orthogonal data for experimental analysis. We have made the predictions available for community perusal.

Project description: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 of 28.5%. 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%, and 26.20%, 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.

Project description:BACKGROUND: The local connectivity and global position of a protein in a protein interaction network are known to correlate with some of its functional properties, including its essentiality or dispensability. It is therefore of interest to extend this observation and examine whether network properties of two proteins considered simultaneously can determine their joint dispensability, i.e., their propensity for synthetic sick/lethal interaction. Accordingly, we examine the predictive power of protein interaction networks for synthetic genetic interaction in Saccharomyces cerevisiae, an organism in which high confidence protein interaction networks are available and synthetic sick/lethal gene pairs have been extensively identified. RESULTS: We design a support vector machine system that uses graph-theoretic properties of two proteins in a protein interaction network as input features for prediction of synthetic sick/lethal interactions. The system is trained on interacting and non-interacting gene pairs culled from large scale genetic screens as well as literature-curated data. We find that the method is capable of predicting synthetic genetic interactions with sensitivity and specificity both exceeding 85%. We further find that the prediction performance is reasonably robust with respect to errors in the protein interaction network and with respect to changes in the features of test datasets. Using the prediction system, we carried out novel predictions of synthetic sick/lethal gene pairs at a genome-wide scale. These pairs appear to have functional properties that are similar to those that characterize the known synthetic lethal gene pairs. CONCLUSION: Our analysis shows that protein interaction networks can be used to predict synthetic lethal interactions with accuracies on par with or exceeding that of other computational methods that use a variety of input features, including functional annotations. This indicates that protein interaction networks could plausibly be rich sources of information about epistatic effects among genes.

Dataset Information

Interspecies data mining to predict novel ING-protein interactions in human.

Publications

Interspecies data mining to predict novel ING-protein interactions in human.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets