In silico analysis of human metabolism : Reconstruction, contextualization and application of genome-scale models

• The arising prevalence of metabolic diseases calls for a holistic approach for analysis of the underlying nature of abnormalities in cellular functions. Through mathematic representation and topological analysis of cellular metabolism, GEnome scale metabolic Models (GEMs) provide a promising framework for uncovering the mechanistic relationship between genotype and phenotype. GEMs hereby enable uncovering associations between cellular physiology and pathology in a systematic manner. Here we review the current progress on reconstruction of human GEMs and how they have been employed as scaffold for interpreting multi-omics high-throughput data with the objective to identify disease-specific metabolic features. We further discuss recent achievements on how to apply these findings for potential target identification and therapeutic drug development. There are, however, challenges in developing models that correctly describe interactions between cells or tissues, and we therefore discuss how GEMs can be integrated with blood circulation models. Finally, we end the review with proposing some possible future research directions.

Ämnesord

NATURVETENSKAP  -- Biologi -- Bioinformatik och systembiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

NATURVETENSKAP  -- Data- och informationsvetenskap -- Bioinformatik (hsv//swe)

NATURAL SCIENCES  -- Computer and Information Sciences -- Bioinformatics (hsv//eng)

Nyckelord

Constraint-based analysis

Drug development

Genome-scale metabolic model

Human metabolism

Topological analysis

bibliometrics

cell interaction

circulation

clinical feature

computer model

conceptual framework

data analysis

data base

drug manufacture

genetic model

GEnome scale metabolic Model

genotype

human

human genome

information processing

liver cell carcinoma

metabolism

metabolite

metabolomics

nonalcoholic fatty liver

phenotype

Review

stoichiometry

tissue interaction

transcriptomics

Publikations- och innehållstyp

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