scholarly journals Defining and Evaluating Microbial Contributions to Metabolite Variation in Microbiome-Metabolome Association Studies

2018 ◽  
Author(s):  
Cecilia Noecker ◽  
Hsuan-Chao Chiu ◽  
Colin P. McNally ◽  
Elhanan Borenstein
Keyword(s):  
Microbial Community ◽  
Predictive Value ◽  
Association Studies ◽  
Ground Truth ◽  
Metabolic Model ◽  
Research Approach ◽  
Mathematical Framework ◽  
Microbial Taxon ◽  
Metabolic Variation ◽  
Definition Of

AbstractCorrelation-based analysis of paired microbiome-metabolome datasets is becoming a widespread research approach, aiming to comprehensively identify microbial drivers of metabolic variation. To date, however, the limitations of this approach have not been comprehensively evaluated. To address this challenge, we introduce a mathematical framework to quantify the contribution of each taxon to metabolite variation based on uptake and secretion fluxes. We additionally use a multi-species metabolic model to simulate simplified gut communities, generating idealized microbiome-metabolome datasets. We then compare observed taxon-metabolite correlations in these datasets to calculated ground-truth taxonomic contribution values. We find that in simulations of both a model 10-species community and of complex human gut microbiota, correlation-based analysis poorly identifies key contributors, with extremely low predictive value despite the idealized setting. We further demonstrate that the predictive value of correlation analysis is strongly influenced by both metabolite and taxon properties, as well as exogenous environmental variation. We finally discuss the practical implications of our findings for interpreting microbiome-metabolome studies.ImportanceIdentifying the key microbial taxa responsible for metabolic differences between microbiomes is an important step towards understanding and manipulating microbiome metabolism. To achieve this goal, researchers commonly conduct microbiome-metabolome association studies, comprehensively measuring both the composition of species and the concentration of metabolites across a set of microbial community samples, and then testing for correlations between microbes and metabolites. Here, we evaluated the utility of this general approach by first developing a rigorous mathematical definition of the contribution of each microbial taxon to metabolite variation, and then examining these contributions in simulated datasets of microbial community metabolism. We found that standard correlation-based analysis of our simulated microbiome-metabolome datasets identifies true contributions with very low predictive value, and that its performance depends strongly on specific properties of both metabolites and microbes, as well as on the surrounding environment. Combined, our findings can guide future interpretation and validation of microbiome-metabolome studies.

scholarly journals Defining and Evaluating Microbial Contributions to Metabolite Variation in Microbiome-Metabolome Association Studies

mSystems ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Cecilia Noecker ◽  
Hsuan-Chao Chiu ◽  
Colin P. McNally ◽  
Elhanan Borenstein
Keyword(s):  
Microbial Community ◽  
Predictive Value ◽  
Association Studies ◽  
Simulated Data ◽  
Ground Truth ◽  
Research Approach ◽  
Data Sets ◽  
Mathematical Framework ◽  
Metabolome Analysis ◽  
Metabolome Data

ABSTRACT Correlation-based analysis of paired microbiome-metabolome data sets is becoming a widespread research approach, aiming to comprehensively identify microbial drivers of metabolic variation. To date, however, the limitations of this approach and other microbiome-metabolome analysis methods have not been comprehensively evaluated. To address this challenge, we have introduced a mathematical framework to quantify the contribution of each taxon to metabolite variation based on uptake and secretion fluxes. We additionally used a multispecies metabolic model to simulate simplified gut communities, generating idealized microbiome-metabolome data sets. We then compared observed taxon-metabolite correlations in these data sets to calculated ground truth taxonomic contribution values. We found that in simulations of both a representative simple 10-species community and complex human gut microbiota, correlation-based analysis poorly identified key contributors, with an extremely low predictive value despite the idealized setting. We further demonstrate that the predictive value of correlation analysis is strongly influenced by both metabolite and taxon properties, as well as by exogenous environmental variation. We finally discuss the practical implications of our findings for interpreting microbiome-metabolome studies. IMPORTANCE Identifying the key microbial taxa responsible for metabolic differences between microbiomes is an important step toward understanding and manipulating microbiome metabolism. To achieve this goal, researchers commonly conduct microbiome-metabolome association studies, comprehensively measuring both the composition of species and the concentration of metabolites across a set of microbial community samples and then testing for correlations between microbes and metabolites. Here, we evaluated the utility of this general approach by first developing a rigorous mathematical definition of the contribution of each microbial taxon to metabolite variation and then examining these contributions in simulated data sets of microbial community metabolism. We found that standard correlation-based analysis of our simulated microbiome-metabolome data sets can identify true contributions with very low predictive value and that its performance depends strongly on specific properties of both metabolites and microbes, as well as on those of the surrounding environment. Combined, our findings can guide future interpretation and validation of microbiome-metabolome studies.

scholarly journals A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression

Metabolites ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 456
Author(s):  
Pejman Salahshouri ◽  
Modjtaba Emadi-Baygi ◽  
Mahdi Jalili ◽  
Faiz M. Khan ◽  
Olaf Wolkenhauer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Gut Microbiome ◽  
Metabolic Model ◽  
System Level ◽  
Mathematical Framework ◽  
Bacterial Populations ◽  
Colorectal Cancer Progression ◽  
Genome Scale ◽  
High Throughput Data Analysis

The human gut microbiota plays a dual key role in maintaining human health or inducing disorders, for example, obesity, type 2 diabetes, and cancers such as colorectal cancer (CRC). High-throughput data analysis, such as metagenomics and metabolomics, have shown the diverse effects of alterations in dynamic bacterial populations on the initiation and progression of colorectal cancer. However, it is well established that microbiome and human cells constantly influence each other, so it is not appropriate to study them independently. Genome-scale metabolic modeling is a well-established mathematical framework that describes the dynamic behavior of these two axes at the system level. In this study, we created community microbiome models of three conditions during colorectal cancer progression, including carcinoma, adenoma and health status, and showed how changes in the microbial population influence intestinal secretions. Conclusively, our findings showed that alterations in the gut microbiome might provoke mutations and transform adenomas into carcinomas. These alterations include the secretion of mutagenic metabolites such as H2S, NO compounds, spermidine and TMA, as well as the reduction of butyrate. Furthermore, we found that the colorectal cancer microbiome can promote inflammation, cancer progression (e.g., angiogenesis) and cancer prevention (e.g., apoptosis) by increasing and decreasing certain metabolites such as histamine, glutamine and pyruvate. Thus, modulating the gut microbiome could be a promising strategy for the prevention and treatment of CRC.

scholarly journals CONCEPTUAL DESIGN FOR ASSEMBLY IN AEROSPACE INDUSTRY: SENSITIVITY ANALYSIS OF MATHEMATICAL FRAMEWORK AND DESIGN PARAMETERS

2021 ◽  
Vol 1 ◽  
pp. 731-740
Author(s):  
Giovanni Formentini ◽  
Claudio Favi ◽  
Claude Cuiller ◽  
Pierre-Eric Dereux ◽  
Francois Bouissiere ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Conceptual Design ◽  
Design Parameters ◽  
Design For Assembly ◽  
Mathematical Framework ◽  
Commercial Aircraft ◽  
System Architectures ◽  
Complex Engineering ◽  
Aircraft System ◽  
Definition Of

AbstractOne of the most challenging activity in the engineering design process is the definition of a framework (model and parameters) for the characterization of specific processes such as installation and assembly. Aircraft system architectures are complex structures used to understand relation among elements (modules) inside an aircraft and its evaluation is one of the first activity since the conceptual design. The assessment of aircraft architectures, from the assembly perspective, requires parameter identification as well as the definition of the overall analysis framework (i.e., mathematical models, equations).The paper aims at the analysis of a mathematical framework (structure, equations and parameters) developed to assess the fit for assembly performances of aircraft system architectures by the mean of sensitivity analysis (One-Factor-At-Time method). The sensitivity analysis was performed on a complex engineering framework, i.e. the Conceptual Design for Assembly (CDfA) methodology, which is characterized by level, domains and attributes (parameters). A commercial aircraft cabin system was used as a case study to understand the use of different mathematical operators as well as the way to cluster attributes.

Ex Vivo assessment of competent strut coverage after coronary stenting by optical coherence tomography

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Bhoite ◽  
H Jinnouchi ◽  
F Otsuka ◽  
Y Sato ◽  
A Sakamoto ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Predictive Value ◽  
Ex Vivo ◽  
High Sensitivity ◽  
Optical Coherence ◽  
Cross Sectional ◽  
Neointimal Thickness ◽  
Stent Strut ◽  
Oct Imaging ◽  
Definition Of

Abstract Background In many studies, struts coverage is defined as >0 mm of tissue overlying the stent struts by optical coherence tomography (OCT). However, this definition has never been validated using histology as the “gold standard”. The present study sought to assess the appropriate cut-off value of neointimal thickness of stent strut coverage by OCT using histology. Methods OCT imaging was performed on 39 human coronary arteries with stents from 25 patients at autopsy. A total of 165 cross-sectional images from 46 stents were co-registered with histology. The optimal cut-off value of strut coverage by OCT was determined. Strut coverage by histology was defined as endothelial cells with at least underlying two layers of smooth muscle cells. Considering the resolution of OCT is 10–20 μm, 3 different cut-off values (i.e. at ≥20, ≥40, and ≥60 μm) were assessed. Results A total of 2235 struts were evaluated by histology. Eventually, 1216 struts which were well-matched struts were analyzed in this study. By histology, uncovered struts were observed in 160 struts and covered struts were observed in 1056 struts. The broadly used definition of OCT-coverage which does not consider neointimal thickness yielded a poor specificity of 37.5% and high sensitivity 100%. Of 3 cut-off values, the cut-off value of >40 μm was more accurate as compared to >20 and >60 mm [sensitivity (99.3%), specificity (91.0%), positive predictive value (98.6%), and negative predictive value (95.6%)] Conclusion The most accurate cut-off value was ≥40 μm neointimal thickness by OCT in order to identify stent strut coverage validated by histology. Funding Acknowledgement Type of funding source: None

scholarly journals Genetic distance as an alternative to physical distance for definition of gene units in association studies

BMC Genomics ◽  
2014 ◽  
Vol 15 (1) ◽  
pp. 408 ◽  
Author(s):  
Cristina Rodriguez-Fontenla ◽  
Manuel Calaza ◽  
Antonio Gonzalez
Keyword(s):  
Genetic Distance ◽  
Association Studies ◽  
Physical Distance ◽  
Definition Of

scholarly journals Safeguarding information as an asset: Do we need a redefinition in the knowledge economy and beyond?

2016 ◽  
Vol 18 (1) ◽  
Author(s):  
Adeniji K. Adesemowo ◽  
Rossouw Von Solms ◽  
Reinhard A. Botha
Keyword(s):  
Internal Control ◽  
Knowledge Economy ◽  
Large Body ◽  
Research Approach ◽  
Significant Finding ◽  
Information Risk ◽  
Starting Point ◽  
Information Assets ◽  
Definition Of ◽  
Definition Of Information

Background: With the evolution of data, via information into knowledge and beyond, intangible information assets (seen as an integral part of IT assets in this article) increasingly come to fore. A contemporary issue facing organisations in the knowledge economy and beyond is how best to safeguard and derive optimum value from their evolving information assets. A well-known fact is that risk exists because there is the possibility of threats to an asset. Likewise, no assets equals no risk. Although a large body of work is addressing threat models, the nature of the assets of the knowledge economy and beyond has not been well researched.Objectives: To investigate the definition of information assets across a number of financial, risk and information technology standards, frameworks and regulations, in order to ascertain whether a coherent definition exists across the board. If there is none (or limited), then propose a workable definition that is apt for the knowledge economy and beyond.Method: Qualitative thematic content analysis and a comparative study based on four main themes (Assets, Types of Asset, Information, and Information Assets). This then serves as a basis for argumentation schemes that lead to a proposed re-definition. The qualitative research approach assists us to address the concern of the incoherent definition of information and information assets across the board.Results: Contrary to expectations, the research study found the current definition to be incoherent. When the asset to be controlled is not properly defined and understood, it stands the risk of not being identified properly. This implies that the effectiveness, efficiency, reliability of internal control, and compliance with the applicable legislation and regulations would not be appropriate. This article highlights the need for a fundamental shift in how information assets (valuable, but unvalued organisational intangible assets) are being viewed and treated, especially with regard to information risk and internal controls.Conclusion: This article has identified a major defect in most standards, frameworks, and regulations dealing with regard to the safeguarding and management of information assets (and IT assets). It has established from the review carried out that information assets have not been properly defined across the board. Beyond this significant finding, it was further shown that the principle of risk (assessment) across the board requires the identification of the asset that needs to be controlled. A starting point, then, is a coherent definition (as proposed) for the information asset in itself. Therefore, proper definition across the board might assists in proper identification that could result in appropriate control and graceful handling of the end-of-life disposal.Keywords: infonomics; information asset; information risk; internal control; reputation loss

scholarly journals Tinjauan Yuridis Terhadap Pendaftaran Dan Penerbitan Sertipikat Tanah Bengkok

2021 ◽  
Vol 7 (1) ◽  
pp. 439
Author(s):  
Lailatul Jannah ◽  
Mega Tri Herawati ◽  
Istiana Rachmawati
Keyword(s):  
Asset Management ◽  
Research Approach ◽  
Conceptual Approach ◽  
Research Results ◽  
The Republic ◽  
Village Government ◽  
Definition Of ◽  
The Village

Bengkok land is village property in the form of village land. This bent land is widely known as village treasury land or village property. The definition of bent land itself is not explicitly regulated in statutory regulations. The definition of crooked land is implicitly regulated by statutory regulations. Based on the explanation of Article 72 of Law Number 6 of 2014 concerning Villages (hereinafter referred to as the Village Law), it is stated that bent land is the result of business. The provisions in Law Number 6 of 2014 concerning Villages indicate that Village Treasury Land or village assets which include bent land are certified in the name of the Village Government. In addition, the Regulation of the Minister of Home Affairs of the Republic of Indonesia Number 1 of 2016 concerning Village Asset Management, regulates the same thing as Law Number 6 of 2014 concerning Villages. This research approach uses a statutory approach (statute approach) and a conceptual approach (conceptual approach). Based on the research results, which crooked land that is starting to lose its existence is certified in the name of the Village Government

scholarly journals An Exploration of Digital Fashion in Pandemic Italy: Districts, Designers, and Displays

2021 ◽  
Author(s):  
Keyword(s):  
Digital Technologies ◽  
Field Research ◽  
Research Approach ◽  
Technological Changes ◽  
Design Production ◽  
Definition Of ◽  
Fashion Designers ◽  
Cultural Media ◽  
Made In

Change is at the heart of the definition of fashion, as many theorists, designers and cultural analysts have shown. This article takes up this perspective to question the role of fashion design in the 21st century in the relation to cultural, media and technological changes. Adopting a field research approach, the paper analyses the interaction between fashion, designers and digital technologies that are emerging in Italy in order to re-grasp Made in Italy in a futuring perspective. The case studies were selected for their relevance to the digital in terms of design, production, and display. The paper analyses that the pandemic crisis is having on the Made in Italy, stimulating new ways of designing, understanding, producing, and consuming fashion.

Training a Team with Simulated Team Members

2002 ◽  
Vol 46 (25) ◽  
pp. 2026-2029
Author(s):  
Alma Schaafstal ◽  
Raegan M. Hoeft ◽  
Martin van Schaik
Keyword(s):  
Command And Control ◽  
Cost Effective ◽  
Research Approach ◽  
Control Task ◽  
Promising Alternative ◽  
Team Members ◽  
Long Run ◽  
Military Command ◽  
Definition Of ◽  
And Control

The process of training teams increasingly occurs in synthetic environments. However, it is often still modeled after live team training, including the disadvantages of live training, for example, the fact that all teammates must be available. This paper explores overcoming the disadvantages of human teammates in training teams in synthetic environments, while keeping the advantages of learning in a collaborative and cooperative fashion. Simulated teammates are a promising alternative because they are always available, may be modeled after experienced training personnel, and may be more cost effective in the long run. This paper details a research approach towards the definition of requirements for simulated teammates. In our approach, we carry out a set of experiments using confederates as simulated teammates, in a well-controlled simulation of a military command-and-control task The results of a first experiment show slightly better teamwork skills for those teams trained with simulated teammates.

Valutare per decidere: un monitoraggio qualitativo degli investimenti pubblici

2009 ◽  
pp. 69-80
Author(s):  
Fausta Scardigno ◽  
Caterina Balenzano ◽  
Giuseppe Moro
Keyword(s):  
Research Design ◽  
Evaluation Process ◽  
Decision Processes ◽  
Research Approach ◽  
Structured Interviews ◽  
Group Discussions ◽  
Evaluation Question ◽  
Participative Approach ◽  
Definition Of ◽  
The Relationship

- This paper suggests some considerations regarding the relationship between evaluation and making decision processes, through the description of an evaluation experience of some formative projects orientated towards unemployed young people living in Apulia Region. After the definition of evaluation question, made together with Educational Local Authority, we have preferred a qualitative research approach. Sharing a participative approach, we have chosen a multistakeholder research design as instrument to catch the representations of actors involved regarding the evolution of projects, the weak and strong aspects, through to focus group discussions and semi-structured interviews respectively administered to actuators and beneficiaries of these projects. Interviews have been analyzed first trough content analysis of relevance and in a second moment trough associations analysis between words, by the use of T-Lab software. Highlighting stakeholders' suggestions and recommendations and giving back them to the decision maker confirms the utility of evaluation as instrument to supporting making decision processes, with the aim of improving policies.Key words: partecipate evaluation, multistakeholder research design, utilization of evaluation Process

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