title: FROG Analysis Ensures the Reproducibility of Genome Scale Metabolic Models
Creators: name: Raman, Karthik
name: Kratochv�L, Miroslav
name: Olivier, Brett G.
name: K�Nig, Matthias
name: Sengupta, Pratyay
name: Baskaran, Dinesh Kumar Kuppa
name: Nguyen, Tung V. N.
name: Lobo, Daniel
name: Wilken, St Elmo
name: Tiwari, Krishna Kumar
name: Raghu, Aswathy K.
name: Palanikumar, Indumathi
name: Raajaraam, Lavanya
name: Ibrahim, Maziya
name: Balakrishnan, Sanjaay
name: Umale, Shreyansh
name: Bergmann, Frank
name: Malpani, Tanisha
name: Satagopam, Venkata P.
name: Schneider, Reinhard
name: Beber, Moritz E.
name: Keating, Sarah
name: Anton, Mihail
name: Renz, Alina
name: Lakshmanan, Meiyappan
name: Lee, Dong-Yup
name: Koduru, Lokanand
name: Mostolizadeh, Reihaneh
name: Dias, Oscar
name: Cunha, Emanuel
name: Oliveira, Alexandre
name: Lee, Yi Qing
name: Zengler, Karsten
name: Santib��Ez-Palominos, Rodrigo
name: Kumar, Manish
name: Barberis, Matteo
name: Puniya, Bhanwar Lal
name: Helikar, Tom�?
name: Dinh, Hoang V.
name: Suthers, Patrick F.
name: Maranas, Costas D.
name: Casini, Isabella
name: Loghmani, Seyed Babak
name: Veith, Nadine
name: Leonidou, Nantia
name: Li, Feiran
name: Chen, Yu
name: Nielsen, Jens
name: Lee, GaRyoung
name: Lee, Sang Mi
name: Kim, Gi Bae
name: Monteiro, Pedro T.
name: Teixeira, Miguel C.
name: Kim, Hyun Uk
name: Lee, Sang Yup
name: Liebal, Ulf W.
name: Blank, Lars M.
name: Lieven, Christian
name: Tarzi, Chaimaa
name: Angione, Claudio
name: Blaise, Manga Enuh
name: Aytar, �Elik P?Nar
name: Kulyashov, Mikhail
name: Akberdin, Llya
name: Kim, Dohyeon
name: Yoon, Sung Ho
name: Xu, Zhaohui
name: Gautam, Jyotshana
name: Scott, William T.
name: Schaap, Peter J.
name: Koehorst, Jasper J.
name: Zu�Iga, Cristal
name: Canto-Encalada, Gabriela
name: Benito-Vaquerizo, Sara
name: Olm, Ivette Parera
name: Suarez-Diez, Maria
name: Yuan, Qianqian
name: Ma, Hongwu
name: Islam, Mohammad Mazharul
name: Papin, Jason A.
name: Zorrilla, Francisco
name: Patil, Kiran Raosaheb
name: Basile, Arianna
name: Nogales, Juan
name: Le�N, Granado San
name: Castillo-Alfonso, Freddy
name: Olivares-Hern�Ndez, Roberto
name: Canto-Encalada, Gabriela
name: Vigueras-Ram�Rez, Gabriel
name: Hermjakob, Henning
name: Dr�Ger, Andreas
name: Malik-Sheriff, Rahuman S.
Publisher: name: Maryland Shared Open Access Repository
Year: 2024

description: Genome-scale metabolic models (GEMs) and other constraint-based models (CBMs) play a pivotal role in understanding biological phenotypes and advancing research in areas like metabolic engineering, human disease modelling, drug discovery, and personalized medicine. Despite their growing application, a significant challenge remains in ensuring the reproducibility of GEMs, primarily due to inconsistent reporting and inadequate model documentation of model results. Addressing this gap, we introduce FROG analysis, a community-driven initiative aimed at standardizing reproducibility assessments of CBMs and GEMs. The FROG framework encompasses four key analyses?Flux variability, Reaction deletion, Objective function, and Gene deletion?to produce standardized, numerically reproducible FROG reports. These reports serve as reference datasets, enabling model evaluators, curators, and independent researchers to verify the reproducibility of GEMs systematically.BioModels, a leading repository of systems biology models, has integrated FROG analysis into its curation workflow, enhancing the reproducibility and reusability of submitted GEMs. In our study evaluating 65 GEM submissions from the community, approximately 40% reproduced without intervention, 28% requiring minor adjustments, and 32% needing input from authors. The standardization introduced by FROG analysis facilitated the detection and resolution of issues, ultimately leading to the successful reproduction of all models. By establishing a standardized and comprehensive approach to evaluating GEM reproducibility, FROG analysis significantly contributes to making CBMs and GEMs more transparent, reusable, and reliable for the broader scientific community.