Reliability prediction of ontology-based service compositions using Petri net and time series models.
Ontology highlight
ABSTRACT:
SUBMITTER: Li J
PROVIDER: S-EPMC3933393 | biostudies-other | 2014
REPOSITORIES: biostudies-other
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Project description:BACKGROUND:Muscle atrophy, an involuntary loss of muscle mass, is involved in various diseases and sometimes leads to mortality. However, therapeutics for muscle atrophy thus far have had limited effects. Here, we present a new approach for therapeutic target prediction using Petri net simulation of the status of phosphorylation, with a reasonable assumption that the recovery of abnormally phosphorylated proteins can be a treatment for muscle atrophy. RESULTS:The Petri net model was employed to simulate phosphorylation status in three states, i.e. reference, atrophic and each gene-inhibited state based on the myocyte-specific phosphorylation network. Here, we newly devised a phosphorylation specific Petri net that involves two types of transitions (phosphorylation or de-phosphorylation) and two types of places (activation with or without phosphorylation). Before predicting therapeutic targets, the simulation results in reference and atrophic states were validated by Western blotting experiments detecting five marker proteins, i.e. RELA, SMAD2, SMAD3, FOXO1 and FOXO3. Finally, we determined 37 potential therapeutic targets whose inhibition recovers the phosphorylation status from an atrophic state as indicated by the five validated marker proteins. In the evaluation, we confirmed that the 37 potential targets were enriched for muscle atrophy-related terms such as actin and muscle contraction processes, and they were also significantly overlapping with the genes associated with muscle atrophy reported in the Comparative Toxicogenomics Database (p-value <?0.05). Furthermore, we noticed that they included several proteins that could not be characterized by the shortest path analysis. The three potential targets, i.e. BMPR1B, ROCK, and LEPR, were manually validated with the literature. CONCLUSIONS:In this study, we suggest a new approach to predict potential therapeutic targets of muscle atrophy with an analysis of phosphorylation status simulated by Petri net. We generated a list of the potential therapeutic targets whose inhibition recovers abnormally phosphorylated proteins in an atrophic state. They were evaluated by various approaches, such as Western blotting, GO terms, literature, known muscle atrophy-related genes and shortest path analysis. We expect the new proposed strategy to provide an understanding of phosphorylation status in muscle atrophy and to provide assistance towards identifying new therapies.
| S-EPMC5838966 | biostudies-literature
Project description:Yield prediction for crops is essential information for food security. A high-throughput phenotyping platform (HTPP) generates the data of the complete life cycle of a plant. However, the data are rarely used for yield prediction because of the lack of quality image analysis methods, yield data associated with HTPP, and the time-series analysis method for yield prediction. To overcome limitations, this study employed multiple deep learning (DL) networks to extract high-quality HTTP data, establish an association between HTTP data and the yield performance of crops, and select essential time intervals using machine learning (ML). The images of Arabidopsis were taken 12 times under environmentally controlled HTPP over 23 days after sowing (DAS). First, the features from images were extracted using DL network U-Net with SE-ResXt101 encoder and divided into early (15-21 DAS) and late (∼21-23 DAS) pre-flowering developmental stages using the physiological characteristics of the Arabidopsis plant. Second, the late pre-flowering stage at 23 DAS can be predicted using the ML algorithm XGBoost, based only on a portion of the early pre-flowering stage (17-21 DAS). This was confirmed using an additional biological experiment (P < 0.01). Finally, the projected area (PA) was estimated into fresh weight (FW), and the correlation coefficient between FW and predicted FW was calculated as 0.85. This was the first study that analyzed time-series data to predict the FW of related but different developmental stages and predict the PA. The results of this study were informative and enabled the understanding of the FW of Arabidopsis or yield of leafy plants and total biomass consumed in vertical farming. Moreover, this study highlighted the reduction of time-series data for examining interesting traits and future application of time-series analysis in various HTPPs.
| S-EPMC8631871 | biostudies-literature
Project description:BackgroundWith an accumulation of in silico data obtained by simulating large-scale biological networks, a new interest of research is emerging for elucidating how living organism functions over time in cells. Investigating the dynamic features of current computational models promises a deeper understanding of complex cellular processes. This leads us to develop a method that utilizes structural properties of the model over all simulation time steps. Further, user-friendly overviews of dynamic behaviors can be considered to provide a great help in understanding the variations of system mechanisms.ResultsWe propose a novel method for constructing and analyzing a so-called active state transition diagram (ASTD) by using time-course simulation data of a high-level Petri net. Our method includes two new algorithms. The first algorithm extracts a series of subnets (called temporal subnets) reflecting biological components contributing to the dynamics, while retaining positive mathematical qualities. The second one creates an ASTD composed of unique temporal subnets. ASTD provides users with concise information allowing them to grasp and trace how a key regulatory subnet and/or a network changes with time. The applicability of our method is demonstrated by the analysis of the underlying model for circadian rhythms in Drosophila.ConclusionsBuilding ASTD is a useful means to convert a hybrid model dealing with discrete, continuous and more complicated events to finite time-dependent states. Based on ASTD, various analytical approaches can be applied to obtain new insights into not only systematic mechanisms but also dynamics.
| S-EPMC2855528 | biostudies-literature
Project description:Statistical prediction models inform decision-making processes in many real-world settings. Prior to using predictions in practice, one must rigorously test and validate candidate models to ensure that the proposed predictions have sufficient accuracy to be used in practice. In this paper, we present a framework for evaluating time series predictions that emphasizes computational simplicity and an intuitive interpretation using the relative mean absolute error metric. For a single time series, this metric enables comparisons of candidate model predictions against naïve reference models, a method that can provide useful and standardized performance benchmarks. Additionally, in applications with multiple time series, this framework facilitates comparisons of one or more models' predictive performance across different sets of data. We illustrate the use of this metric with a case study comparing predictions of dengue hemorrhagic fever incidence in two provinces of Thailand. This example demonstrates the utility and interpretability of the relative mean absolute error metric in practice, and underscores the practical advantages of using relative performance metrics when evaluating predictions.
| S-EPMC5270768 | biostudies-other
Project description:INF-? has been widely used to treat patients with multiple sclerosis (MS) in relapse. Accurate prediction of treatment response is important for effective personalization of treatment. Microarray data have been frequently used to discover new genes and to predict treatment responses. However, conventional analytical methods suffer from three difficulties: high-dimensionality of datasets; high degree of multi-collinearity; and achieving gene identification in time-course data. The use of Elastic net, a sparse modelling method, would decrease the first two issues; however, Elastic net is currently unable to solve these three issues simultaneously. Here, we improved Elastic net to accommodate time-course data analyses. Numerical experiments were conducted using two time-course microarray datasets derived from peripheral blood mononuclear cells collected from patients with MS. The proposed methods successfully identified genes showing a high predictive ability for INF-? treatment response. Bootstrap sampling resulted in an 81% and 78% accuracy for each dataset, which was significantly higher than the 71% and 73% accuracy obtained using conventional methods. Our methods selected genes showing consistent differentiation throughout all time-courses. These genes are expected to provide new predictive biomarkers that can influence INF-? treatment for MS patients.
| S-EPMC6372673 | biostudies-literature
Project description:Microbiome data are becoming increasingly available in large health cohorts, yet metabolomics data are still scant. While many studies generate microbiome data, they lack matched metabolomics data or have considerable missing proportions of metabolites. Since metabolomics is key to understanding microbial and general biological activities, the possibility of imputing individual metabolites or inferring metabolomics pathways from microbial taxonomy or metagenomics is intriguing. Importantly, current metabolomics profiling methods such as the HMP Unified Metabolic Analysis Network (HUMAnN) have unknown accuracy and are limited in their ability to predict individual metabolites. To address this gap, we developed a novel metabolite prediction method, and we present its application and evaluation in an oral microbiome study. The new method for predicting metabolites using microbiome data (ENVIM) is based on the elastic net model (ENM). ENVIM introduces an extra step to ENM to consider variable importance (VI) scores, and thus, achieves better prediction power. We investigate the metabolite prediction performance of ENVIM using metagenomic and metatranscriptomic data in a supragingival biofilm multi-omics dataset of 289 children ages 3-5 who were participants of a community-based study of early childhood oral health (ZOE 2.0) in North Carolina, United States. We further validate ENVIM in two additional publicly available multi-omics datasets generated from studies of gut health. We select gene family sets based on variable importance scores and modify the existing ENM strategy used in the MelonnPan prediction software to accommodate the unique features of microbiome and metabolome data. We evaluate metagenomic and metatranscriptomic predictors and compare the prediction performance of ENVIM to the standard ENM employed in MelonnPan. The newly developed ENVIM method showed superior metabolite predictive accuracy than MelonnPan when trained with metatranscriptomics data only, metagenomics data only, or both. Better metabolite prediction is achieved in the gut microbiome compared with the oral microbiome setting. We report the best-predictable compounds in all these three datasets from two different body sites. For example, the metabolites trehalose, maltose, stachyose, and ribose are all well predicted by the supragingival microbiome.
| S-EPMC8573316 | biostudies-literature
Project description:BackgroundStructural analysis of biochemical networks is a growing field in bioinformatics and systems biology. The availability of an increasing amount of biological data from molecular biological networks promises a deeper understanding but confronts researchers with the problem of combinatorial explosion. The amount of qualitative network data is growing much faster than the amount of quantitative data, such as enzyme kinetics. In many cases it is even impossible to measure quantitative data because of limitations of experimental methods, or for ethical reasons. Thus, a huge amount of qualitative data, such as interaction data, is available, but it was not sufficiently used for modeling purposes, until now. New approaches have been developed, but the complexity of data often limits the application of many of the methods. Biochemical Petri nets make it possible to explore static and dynamic qualitative system properties. One Petri net approach is model validation based on the computation of the system's invariant properties, focusing on t-invariants. T-invariants correspond to subnetworks, which describe the basic system behavior.With increasing system complexity, the basic behavior can only be expressed by a huge number of t-invariants. According to our validation criteria for biochemical Petri nets, the necessary verification of the biological meaning, by interpreting each subnetwork (t-invariant) manually, is not possible anymore. Thus, an automated, biologically meaningful classification would be helpful in analyzing t-invariants, and supporting the understanding of the basic behavior of the considered biological system.MethodsHere, we introduce a new approach to automatically classify t-invariants to cope with network complexity. We apply clustering techniques such as UPGMA, Complete Linkage, Single Linkage, and Neighbor Joining in combination with different distance measures to get biologically meaningful clusters (t-clusters), which can be interpreted as modules. To find the optimal number of t-clusters to consider for interpretation, the cluster validity measure, Silhouette Width, is applied.ResultsWe considered two different case studies as examples: a small signal transduction pathway (pheromone response pathway in Saccharomyces cerevisiae) and a medium-sized gene regulatory network (gene regulation of Duchenne muscular dystrophy). We automatically classified the t-invariants into functionally distinct t-clusters, which could be interpreted biologically as functional modules in the network. We found differences in the suitability of the various distance measures as well as the clustering methods. In terms of a biologically meaningful classification of t-invariants, the best results are obtained using the Tanimoto distance measure. Considering clustering methods, the obtained results suggest that UPGMA and Complete Linkage are suitable for clustering t-invariants with respect to the biological interpretability.ConclusionWe propose a new approach for the biological classification of Petri net t-invariants based on cluster analysis. Due to the biologically meaningful data reduction and structuring of network processes, large sets of t-invariants can be evaluated, allowing for model validation of qualitative biochemical Petri nets. This approach can also be applied to elementary mode analysis.
| S-EPMC2277402 | biostudies-literature
Project description:Cellular DNA is daily exposed to several damaging agents causing a plethora of DNA lesions. As a first aid to restore DNA integrity, several enzymes got specialized in damage recognition and lesion removal during the process called base excision repair (BER). A large number of DNA damage types and several different readers of nucleic acids lesions during BER pathway as well as two sub-pathways were considered in the definition of a model using the Petri net framework. The intuitive graphical representation in combination with precise mathematical analysis methods are the strong advantages of the Petri net-based representation of biological processes and make Petri nets a promising approach for modeling and analysis of human BER. The reported results provide new information that will aid efforts to characterize in silico knockouts as well as help to predict the sensitivity of the cell with inactivated repair proteins to different types of DNA damage. The results can also help in identifying the by-passing pathways that may lead to lack of pronounced phenotypes associated with mutations in some of the proteins. This knowledge is very useful when DNA damage-inducing drugs are introduced for cancer therapy, and lack of DNA repair is desirable for tumor cell death.
| S-EPMC6743755 | biostudies-literature
Project description:Temporal and technical variability of human gut metagenomes
| PRJEB8347 | ENA
Project description:Fungal control of early-stage bacterial community development in wood
| PRJEB87091 | ENA