Guided extraction of genome-scale metabolic models for the integration and analysis of omics data

Walakira, Andrew (avtor), Rozman, Damjana (avtor), Režen, Tadeja (avtor), Mraz, Miha (avtor), Moškon, Miha (avtor)

Omics data can be integrated into a reference model using various model extraction methods (MEMs) to yield context-specific genome-scale metabolic models (GEMs). How to chose the appropriate MEM, thresholding rule and threshold remains a challenge. We integrated mouse transcriptomic data from a Cyp51 knockout mice diet experiment (GSE58271) using five MEMs (GIMME, iMAT, FASTCORE, INIT an tINIT) in a combination with a recently published mouse GEM iMM1865. Except for INIT and tINIT, the size of extracted models varied with the MEM used (t-test: p-value <0.001). The Jaccard index of iMAT models ranged from 0.27 to 1.0. Out of the three factors under study in the experiment (diet, gender and genotype), gender explained most of the variability (>90%) in PC1 for FASTCORE. In iMAT, each of the three factors explained less than 40% of the variability within PC1, PC2 and PC3. Among all the MEMs, FASTCORE captured the most of the true variability in the data by clustering samples by gender. Our results show that for the efficient use of MEMs in the context of omics data integration and analysis, one should apply various MEMs, thresholding rules, and thresholding values to select the MEM and its configuration that best captures the true variability in the data. This selection can be guided by the methodology as proposed and used in this paper. Moreover, we describe certain approaches that can be used to analyse the results obtained with the selected MEM and to put these results in a biological context.

• Jezik: Angleški jezik
• Ključne besede: genome-scale metabolic model, model extraction methods, context-specific metabolic model, omics data integration, subsystem enrichment analysis, model interpretability
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta ; FRI - Fakulteta za računalništvo in informatiko
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: Str. 3521-3530
• Številčenje: Vol. 19
• PID: 20.500.12556/RUL-127776
• UDK: 004:575.112
• ISSN pri članku: 2001-0370
• DOI: 10.1016/j.csbj.2021.06.009
• COBISS.SI-ID: 66227971
• Datum objave v RUL: 22.06.2021

Gradivo je del revije

• Naslov: Computational and structural biotechnology journal
• Založnik: Elsevier, Research Network of Computational and Structural Biotechnology
• ISSN: 2001-0370
• COBISS.SI-ID: 5068826

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: metabolni modeli na nivoju genoma, ekstrakcija modelov, kontekstno specifični metabolni modeli, integracija omskih podatkov, analiza obogatitve metabolnih podsistemov