Dataset Information

Application of Monte Carlo cross-validation to identify pathway cross-talk in neonatal sepsis.

ABSTRACT: To explore genetic pathway cross-talk in neonates with sepsis, an integrated approach was used in this paper. To explore the potential relationships between differently expressed genes between normal uninfected neonates and neonates with sepsis and pathways, genetic profiling and biologic signaling pathway were first integrated. For different pathways, the score was obtained based upon the genetic expression by quantitatively analyzing the pathway cross-talk. The paired pathways with high cross-talk were identified by random forest classification. The purpose of the work was to find the best pairs of pathways able to discriminate sepsis samples versus normal samples. The results found 10 pairs of pathways, which were probably able to discriminate neonates with sepsis versus normal uninfected neonates. Among them, the best two paired pathways were identified according to analysis of extensive literature. Impact statement To find the best pairs of pathways able to discriminate sepsis samples versus normal samples, an RF classifier, the DS obtained by DEGs of paired pathways significantly associated, and Monte Carlo cross-validation were applied in this paper. Ten pairs of pathways were probably able to discriminate neonates with sepsis versus normal uninfected neonates. Among them, the best two paired pathways ((7) IL-6 Signaling and Phospholipase C Signaling (PLC); (8) Glucocorticoid Receptor (GR) Signaling and Dendritic Cell Maturation) were identified according to analysis of extensive literature.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC5882034 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Application of Monte Carlo cross-validation to identify pathway cross-talk in neonatal sepsis.

Zhang Yuxia Y Liu Cui C Wang Jingna J Li Xingxia X

Experimental biology and medicine (Maywood, N.J.) 20180301 5

To explore genetic pathway cross-talk in neonates with sepsis, an integrated approach was used in this paper. To explore the potential relationships between differently expressed genes between normal uninfected neonates and neonates with sepsis and pathways, genetic profiling and biologic signaling pathway were first integrated. For different pathways, the score was obtained based upon the genetic expression by quantitatively analyzing the pathway cross-talk. The paired pathways with high cross- ...[more]

PMID: 29513099

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Project description:More than one pathway is involved in disease development and progression, and two or more pathways may be interconnected to further affect the disease onset, as functional proteins participate in multiple pathways. Thus, identifying cross-talk among pathways is necessary to understand the molecular mechanisms of multiple myeloma (MM). Based on this, this paper looked at extracting potential pathway cross-talk in MM through an integrative approach using Monte Carlo cross-validation analysis. The gene expression library of MM (accession number: GSE6477) was downloaded from the Gene Expression Omnibus (GEO) database. The integrative approach was then used to identify potential pathway cross-talk, and included four steps: Firstly, differential expression analysis was conducted to identify differentially expressed genes (DEGs). Secondly, the DEGs obtained were mapped to the pathways downloaded from an ingenuity pathways analysis (IPA), to reveal the underlying relationship between the DEGs and pathways enriched by these DEGs. A subset of pathways enriched by the DEGs was then obtained. Thirdly, a discriminating score (DS) value for each paired pathway was computed. Lastly, random forest (RF) classification was used to identify the paired pathways based on area under the curve (AUC) and Monte Carlo cross-validation, which was repeated 50 times to explore the best paired pathways. These paired pathways were tested with another independently published MM microarray data (GSE85837), using in silico validation. Overall, 60 DEGs and 19 differential pathways enriched by DEGs were extracted. Each pathway was sorted based on their AUC values. The paired pathways, inhibition of matrix metalloproteases and EIF2 signaling pathway, indicated the best AUC value of 1.000. Paired pathways consisting of IL-8 and EIF2 signaling pathways with higher AUC of 0.975, were involved in 7 runs. Furthermore, it was validated consistently in separate microarray data sets (GSE85837). Paired pathways (inhibition of matrix metalloproteases and EIF2 signaling, IL-8 signaling and EIF2 signaling) exhibited the best AUC values and higher frequency of validation. Two paired pathways (inhibition of matrix metalloproteases and EIF2 signaling, IL-8 signaling and EIF2 signaling) were used to accurately classify MM and control samples. These paired pathways may be potential bio-signatures for diagnosis and management of MM.

Project description:We implement a Monte Carlo heuristic algorithm to model drug release from a solid dosage form. We show that with Monte Carlo simulations it is possible to identify and explain the causes of the unsatisfactory predictive power of current drug release models. It is well known that the power-law, the exponential models, as well as those derived from or inspired by them accurately reproduce only the first 60% of the release curve of a drug from a dosage form. In this study, by using Monte Carlo simulation approaches, we show that these models fit quite accurately almost the entire release profile when the release kinetics is not governed by the coexistence of different physico-chemical mechanisms. We show that the accuracy of the traditional models are comparable with those of Monte Carlo heuristics when these heuristics approximate and oversimply the phenomenology of drug release. This observation suggests to develop and use novel Monte Carlo simulation heuristics able to describe the complexity of the release kinetics, and consequently to generate data more similar to those observed in real experiments. Implementing Monte Carlo simulation heuristics of the drug release phenomenology may be much straightforward and efficient than hypothesizing and implementing from scratch complex mathematical models of the physical processes involved in drug release. Identifying and understanding through simulation heuristics what processes of this phenomenology reproduce the observed data and then formalize them in mathematics may allow avoiding time-consuming, trial-error based regression procedures. Three bullet points, highlighting the customization of the procedure. •An efficient heuristics based on Monte Carlo methods for simulating drug release from solid dosage form encodes is presented. It specifies the model of the physical process in a simple but accurate way in the formula of the Monte Carlo Micro Step (MCS) time interval.•Given the experimentally observed curve of drug release, we point out how Monte Carlo heuristics can be integrated in an evolutionary algorithmic approach to infer the mode of MCS best fitting the observed data, and thus the observed release kinetics.•The software implementing the method is written in R language, the free most used language in the bioinformaticians community.

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Application of Monte Carlo cross-validation to identify pathway cross-talk in neonatal sepsis.

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Application of Monte Carlo cross-validation to identify pathway cross-talk in neonatal sepsis.

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