Computational modelling has become increasingly common in life science research. To provide a platform to support universal sharing, easy accessibility and model reproducibility, BioModels (https://www.ebi.ac.uk/biomodels/), a repository for mathematical models, was established in 2005. The current BioModels platform allows submission of models encoded in diverse modelling formats, including SBML, CellML, PharmML, COMBINE archive, MATLAB, Mathematica, R, Python or C++. The models submitted to BioModels are curated to verify the computational representation of the biological process and the reproducibility of the simulation results in the reference publication. The curation also involves encoding models in standard formats and annotation with controlled vocabularies following MIRIAM (minimal information required in the annotation of biochemical models) guidelines. BioModels now accepts large-scale submission of auto-generated computational models. With gradual growth in content over 15 years, BioModels currently hosts about 2000 models from the published literature. With about 800 curated models, BioModels has become the world’s largest repository of curated models and emerged as the third most used data resource after PubMed and Google Scholar among the scientists who use modelling in their research. Thus, BioModels benefits modellers by providing access to reliable and semantically enriched curated models in standard formats that are easy to share, reproduce and reuse.
Reproducibility of scientific results is a key element of science and credibility. The lack of reproducibility across many scientific fields has emerged as an important concern. In this piece, we assess mathematical model reproducibility and propose a scorecard for improving reproducibility in this field.
The reproducibility crisis has emerged as an important concern across many fields of science including life science, since many published results failed to reproduce. Systems biology modelling, which involves mathematical representation of biological processes to study complex system behaviour, was expected to be least affected by this crisis. While lack of reproducibility of experimental results and computational analysis could be a repercussion of several compounded factors, it was not fully understood why systems biology models with well defined mathematical expressions fail to reproduce and how prevalent it is. Hence, we systematically attempted to reproduce 455 kinetic models of biological processes published in peer-reviewed research articles from 152 journals; which is collectively a work of about 1400 scientists from 49 countries. Our investigation revealed that about half (49%) of the models could not be reproduced using the information provided in the published manuscripts. With further effort, an additional 12% of the models could be reproduced either by empirical correction or support from authors. The other 37% remained non-reproducible models due to missing parameter values, missing initial concentration, inconsistent model structure, or a combination of these factors. Among the corresponding authors of the non-reproducible model we contacted, less than 30% responded. Our analysis revealed that models published in journals across several fields of life science failed to reproduce, revealing a common problem in the peer-review process. Hence, we propose an 8-point reproducibility scorecard that can be used by authors, reviewers and journal editors to assess each model and address the reproducibility crisis.
Background: Different formulae have been developed globally for estimation of gestational age (GA) by ultrasonography in the first trimester of pregnancy. In this study, we develop an Indian population-specific dating formula and compare its performance with published formulae. Finally, we evaluate the implications of the choice of dating method on preterm birth (PTB) rate. The data for this study was from GARBH-Ini, an ongoing pregnancy cohort of North Indian women to study PTB. Methods: Comparisons between ultrasonography-Hadlock and last menstrual period (LMP) based dating methods were made by studying the distribution of their differences by Bland-Altman analysis. Using data driven approaches, we removed data outliers more efficiently than by applying clinical parameters. We applied advanced machine learning algorithms to identify relevant features for GA estimation and developed an Indian population-specific formula (Garbhini-1) for the first trimester. PTB rates of Garbhini-1 and other formulae were compared by estimating sensitivity and accuracy. Results: Performance of Garbhini-1 formula, a non-linear function of crown-rump length (CRL), was equivalent to published formulae for estimation of first trimester GA (limits of agreement, -0.46,0.96 weeks). We found that CRL was the most important parameter in estimating GA and no other clinical or socioeconomic covariates contributed to GA estimation. The estimated PTB rate across all the formulae including LMP ranged 11.54-16.50% with Garbhini-1 estimating the least rate with highest sensitivity and accuracy. While LMP-based method overestimated GA by three days compared to USG-Hadlock formula; at an individual level, these methods had less than 50% agreement in classification of PTB. Conclusions: An accurate estimation of GA is crucial for management of PTB. Garbhini-1, the first such formula developed in an Indian setting, estimates PTB rates with higher accuracy especially when compared to commonly used Hadlock formula. Our results reinforce the need to develop population-specific gestational age formulae.
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