Reproducibility in Systems Biology Modelling

Systems biology modelling involves the mathematical representation of biological processes to study complex system behaviour and was expected to be less affected by the reproducibility crisis. However, models often fail to reproduce and the reasons for the failure and prevalence were not fully understood. We analyzed 455 kinetic models published in 152 peer-reviewed journals, a collective work of about 1400 scientists from 49 countries. Most of these models were manually encoded from scratch to assess the reproducibility. Our investigation revealed that 49% of the models could not be reproduced using the information provided in the manuscripts. With further effort, an additional 12% could be reproduced either by empirical correction or support from authors. The other 37% remained non-reproducible due to missing parameter values, missing initial concentration, or inconsistent model structure. Among the corresponding authors, we contacted <30% responded. Models from many life science journals failed to reproduce, revealing a common problem in the peer-review process. Hence, we propose an 8-point reproducibility scorecard (Box 1) to assess each model and address the reproducibility crisis.

Read more:

Tiwari et al. 2020 Reproducibility in systems biology modelling. Mol Syst Biol. (2021) 17: e9982; doi: https://doi.org/10.15252/msb.20209982

Click here to download the Reproducibility Scorecard document

Box1

Reproducibility scorecard

1) Are the mathematical expressions provided and explained in the manuscript/supplementary material?

                  

2) Are the parameters and entity initial levels in the manuscript/supplementary material (e.g., listed as a table)?

 

3) Are simulation conditions including software/programming environment, algorithm, changes in parameters/concentration/states, and any data normalization described under each simulation figure or attached as supplementary material?

 

4) Are the model code(s) for the mathematical expression and simulation shared publicly?

 

5)  Are the model codes shared in standard formats such as SBML, CellML, and COMBINE archive? Are instructions for simulation experiments and analysis available in standard format such as SED-ML? Are they syntactically validated?

 

6) Are the model codes deposited in a relevant open model database (e.g., BioModels, Physiome, JWSOnline)?

 

7) Are the model codes well documented to unambiguously identify model entities/variables? (with additional annotations characterising reactions, mathematical expressions, events, conditions, etc. where relevant.)
For models in standard formats such as SBML and COMBINE Archive: Are files semantically enriched, i.e. annotated with controlled vocabularies such as UniProt, Gene Ontology, ChEBI?

 

8) Are the numerical results shared publicly along with the model codes?

 

Total Score (out of 8)

 

 

List of 455 models analysed in this work and their reproducibility status

R = Reproducible

RMC = Reproduced with model correction

RAH = Reproduced with author help

NRP = Non reproducible

 

Model ID

BioModels link

Reproducibility status

MODEL1812040007

https://identifiers.org/biomodels.db:MODEL1812040007

NRP

MODEL1708310000

https://identifiers.org/biomodels.db:MODEL1708310000

R

MODEL1006230057

https://identifiers.org/biomodels.db:MODEL1006230057

R

MODEL0911270008

https://identifiers.org/biomodels.db:MODEL0911270008

R

MODEL8687732743

https://identifiers.org/biomodels.db:MODEL8687732743

R

MODEL1006230001

https://identifiers.org/biomodels.db:MODEL1006230001

R

MODEL1604270000

https://identifiers.org/biomodels.db:MODEL1604270000

RMC

MODEL1604270001

https://identifiers.org/biomodels.db:MODEL1604270001

RMC

MODEL1708250001

https://identifiers.org/biomodels.db:MODEL1708250001

R

MODEL1006230019

https://identifiers.org/biomodels.db:MODEL1006230019

R

MODEL1006230004

https://identifiers.org/biomodels.db:MODEL1006230004

R

MODEL1006230005

https://identifiers.org/biomodels.db:MODEL1006230005

R

MODEL1006230007

https://identifiers.org/biomodels.db:MODEL1006230007

R

MODEL0912160005

https://identifiers.org/biomodels.db:MODEL0912160005

R

MODEL1006230002

https://identifiers.org/biomodels.db:MODEL1006230002

RMC

MODEL1006230011

https://identifiers.org/biomodels.db:MODEL1006230011

RMC

MODEL1006230098

https://identifiers.org/biomodels.db:MODEL1006230098

RMC

MODEL1006230006

https://identifiers.org/biomodels.db:MODEL1006230006

R

MODEL1006230062

https://identifiers.org/biomodels.db:MODEL1006230062

RMC

MODEL1006230061

https://identifiers.org/biomodels.db:MODEL1006230061

RMC

MODEL1006230094

https://identifiers.org/biomodels.db:MODEL1006230094

R

MODEL1006230086

https://identifiers.org/biomodels.db:MODEL1006230086

R

MODEL1006230052

https://identifiers.org/biomodels.db:MODEL1006230052

R

MODEL1006230097

https://identifiers.org/biomodels.db:MODEL1006230097

R

MODEL1602280002

https://identifiers.org/biomodels.db:MODEL1602280002

RMC

MODEL1602280003

https://identifiers.org/biomodels.db:MODEL1602280003

RMC

MODEL1006230022

https://identifiers.org/biomodels.db:MODEL1006230022

R

MODEL4968912141

https://identifiers.org/biomodels.db:MODEL4968912141

R

MODEL7817907010

https://identifiers.org/biomodels.db:MODEL7817907010

RMC

MODEL1701090001

https://identifiers.org/biomodels.db:MODEL1701090001

RMC

MODEL1511290000

https://identifiers.org/biomodels.db:MODEL1511290000

R

MODEL1006230091

https://identifiers.org/biomodels.db:MODEL1006230091

R

MODEL1803300000

https://identifiers.org/biomodels.db:MODEL1803300000

R

MODEL0848279215

https://identifiers.org/biomodels.db:MODEL0848279215

R

MODEL1006230054

https://identifiers.org/biomodels.db:MODEL1006230054

R

MODEL6960055446

https://identifiers.org/biomodels.db:MODEL6960055446

R

MODEL1202090002

https://identifiers.org/biomodels.db:MODEL1202090002

R

MODEL1202090003

https://identifiers.org/biomodels.db:MODEL1202090003

R

MODEL0913242281

https://identifiers.org/biomodels.db:MODEL0913242281

R

MODEL2504064544

https://identifiers.org/biomodels.db:MODEL2504064544

R

MODEL1703030000

https://identifiers.org/biomodels.db:MODEL1703030000

R

MODEL1112260000

https://identifiers.org/biomodels.db:MODEL1112260000

RMC

MODEL1112260001

https://identifiers.org/biomodels.db:MODEL1112260001

RMC

MODEL1006230047

https://identifiers.org/biomodels.db:MODEL1006230047

R

MODEL1808280004

https://identifiers.org/biomodels.db:MODEL1808280004

R

MODEL1808280002

https://identifiers.org/biomodels.db:MODEL1808280002

R

MODEL1808280003

https://identifiers.org/biomodels.db:MODEL1808280003

R

MODEL1808280005

https://identifiers.org/biomodels.db:MODEL1808280005

R

MODEL1808280001

https://identifiers.org/biomodels.db:MODEL1808280001

R

MODEL1808280012

https://identifiers.org/biomodels.db:MODEL1808280012

RMC

MODEL1808240002

https://identifiers.org/biomodels.db:MODEL1808240002

RAH

MODEL1808240003

https://identifiers.org/biomodels.db:MODEL1808240003

RAH

MODEL1808280008

https://identifiers.org/biomodels.db:MODEL1808280008

R

MODEL1808280009

https://identifiers.org/biomodels.db:MODEL1808280009

R

MODEL1808280010

https://identifiers.org/biomodels.db:MODEL1808280010

R

MODEL2004060002

https://identifiers.org/biomodels.db:MODEL2004060002

R

MODEL2004060001

https://identifiers.org/biomodels.db:MODEL2004060001

R

MODEL1511020000

https://identifiers.org/biomodels.db:MODEL1511020000

R

MODEL1811150001

https://identifiers.org/biomodels.db:MODEL1811150001

RMC

MODEL1811210001

https://identifiers.org/biomodels.db:MODEL1811210001

R

MODEL1812040008

https://identifiers.org/biomodels.db:MODEL1812040008

R

MODEL1809060006

https://identifiers.org/biomodels.db:MODEL1809060006

R

MODEL1811070001

https://identifiers.org/biomodels.db:MODEL1811070001

RMC

MODEL1811080001

https://identifiers.org/biomodels.db:MODEL1811080001

R

MODEL1811220001

https://identifiers.org/biomodels.db:MODEL1811220001

RAH

MODEL1812110002

https://identifiers.org/biomodels.db:MODEL1812110002

RMC

MODEL1812120004

https://identifiers.org/biomodels.db:MODEL1812120004

R

MODEL1812120005

https://identifiers.org/biomodels.db:MODEL1812120005

R

MODEL1812210001

https://identifiers.org/biomodels.db:MODEL1812210001

R

MODEL1901250001

https://identifiers.org/biomodels.db:MODEL1901250001

R

MODEL1006230038

https://identifiers.org/biomodels.db:MODEL1006230038

R

MODEL1605030002

https://identifiers.org/biomodels.db:MODEL1605030002

R

MODEL1605030003

https://identifiers.org/biomodels.db:MODEL1605030003

R

MODEL1605030004

https://identifiers.org/biomodels.db:MODEL1605030004

R

MODEL1605030005

https://identifiers.org/biomodels.db:MODEL1605030005

R

MODEL1903040001

https://identifiers.org/biomodels.db:MODEL1903040001

R

MODEL1807020001

https://identifiers.org/biomodels.db:MODEL1807020001

R

MODEL1808160002

https://identifiers.org/biomodels.db:MODEL1808160002

R

MODEL1907050001

https://identifiers.org/biomodels.db:MODEL1907050001

R

MODEL1907050002

https://identifiers.org/biomodels.db:MODEL1907050002

R

MODEL1907050003

https://identifiers.org/biomodels.db:MODEL1907050003

R

MODEL1907050004

https://identifiers.org/biomodels.db:MODEL1907050004

R

MODEL1907240003

https://identifiers.org/biomodels.db:MODEL1907240003

R

MODEL1907100001

https://identifiers.org/biomodels.db:MODEL1907100001

R

MODEL1907050005

https://identifiers.org/biomodels.db:MODEL1907050005

R

MODEL1907230001

https://identifiers.org/biomodels.db:MODEL1907230001

R

MODEL1807230003

https://identifiers.org/biomodels.db:MODEL1807230003

R

MODEL1907110001

https://identifiers.org/biomodels.db:MODEL1907110001

R

MODEL1907110002

https://identifiers.org/biomodels.db:MODEL1907110002

RMC

MODEL1907230002

https://identifiers.org/biomodels.db:MODEL1907230002

R

MODEL1907160001

https://identifiers.org/biomodels.db:MODEL1907160001

R

MODEL1907160002

https://identifiers.org/biomodels.db:MODEL1907160002

R

MODEL1907170001

https://identifiers.org/biomodels.db:MODEL1907170001

R

MODEL1907180001

https://identifiers.org/biomodels.db:MODEL1907180001

R

MODEL1907230003

https://identifiers.org/biomodels.db:MODEL1907230003

R

MODEL1907180002

https://identifiers.org/biomodels.db:MODEL1907180002

R

MODEL1907240002

https://identifiers.org/biomodels.db:MODEL1907240002

R

MODEL1907240001

https://identifiers.org/biomodels.db:MODEL1907240001

R

MODEL1907220001

https://identifiers.org/biomodels.db:MODEL1907220001

R

MODEL1907180004

https://identifiers.org/biomodels.db:MODEL1907180004

R

MODEL1907240004

https://identifiers.org/biomodels.db:MODEL1907240004

R

MODEL2005110001

https://identifiers.org/biomodels.db:MODEL2005110001

R

MODEL1908130003

https://identifiers.org/biomodels.db:MODEL1908130003

R

MODEL1910250001

https://identifiers.org/biomodels.db:MODEL1910250001

R

MODEL1907250001

https://identifiers.org/biomodels.db:MODEL1907250001

R

MODEL1907260017

https://identifiers.org/biomodels.db:MODEL1907260017

RMC

MODEL1907290001

https://identifiers.org/biomodels.db:MODEL1907290001

R

MODEL1907290002

https://identifiers.org/biomodels.db:MODEL1907290002

R

MODEL1907290003

https://identifiers.org/biomodels.db:MODEL1907290003

R

MODEL1907300001

https://identifiers.org/biomodels.db:MODEL1907300001

R

MODEL1907310004

https://identifiers.org/biomodels.db:MODEL1907310004

R

MODEL1907310003

https://identifiers.org/biomodels.db:MODEL1907310003

R

MODEL1907310005

https://identifiers.org/biomodels.db:MODEL1907310005

R

MODEL1908010001

https://identifiers.org/biomodels.db:MODEL1908010001

R

MODEL1908010003

https://identifiers.org/biomodels.db:MODEL1908010003

R

MODEL1908010002

https://identifiers.org/biomodels.db:MODEL1908010002

R

MODEL1908020001

https://identifiers.org/biomodels.db:MODEL1908020001

R

MODEL1908040001

https://identifiers.org/biomodels.db:MODEL1908040001

R

MODEL1908020002

https://identifiers.org/biomodels.db:MODEL1908020002

R

MODEL1908050002

https://identifiers.org/biomodels.db:MODEL1908050002

R

MODEL1908050001

https://identifiers.org/biomodels.db:MODEL1908050001

R

MODEL1908120002

https://identifiers.org/biomodels.db:MODEL1908120002

R

MODEL1908060001

https://identifiers.org/biomodels.db:MODEL1908060001

R

MODEL1908120004

https://identifiers.org/biomodels.db:MODEL1908120004

RMC

MODEL1908060002

https://identifiers.org/biomodels.db:MODEL1908060002

R

MODEL1908060003

https://identifiers.org/biomodels.db:MODEL1908060003

R

MODEL1908080001

https://identifiers.org/biomodels.db:MODEL1908080001

R

MODEL1908090001

https://identifiers.org/biomodels.db:MODEL1908090001

R

MODEL1908090002

https://identifiers.org/biomodels.db:MODEL1908090002

R

MODEL1908120001

https://identifiers.org/biomodels.db:MODEL1908120001

R

MODEL1908120003

https://identifiers.org/biomodels.db:MODEL1908120003

R

MODEL1908090003

https://identifiers.org/biomodels.db:MODEL1908090003

R

MODEL1908130001

https://identifiers.org/biomodels.db:MODEL1908130001

R

MODEL1908130002

https://identifiers.org/biomodels.db:MODEL1908130002

R

MODEL1908130004

https://identifiers.org/biomodels.db:MODEL1908130004

R

MODEL1908150001

https://identifiers.org/biomodels.db:MODEL1908150001

R

MODEL1908140001

https://identifiers.org/biomodels.db:MODEL1908140001

R

MODEL1908190001

https://identifiers.org/biomodels.db:MODEL1908190001

R

MODEL1908190002

https://identifiers.org/biomodels.db:MODEL1908190002

R

MODEL1908200002

https://identifiers.org/biomodels.db:MODEL1908200002

RMC

MODEL1908200001

https://identifiers.org/biomodels.db:MODEL1908200001

RMC

MODEL1909170002

https://identifiers.org/biomodels.db:MODEL1909170002

RAH

MODEL1908190003

https://identifiers.org/biomodels.db:MODEL1908190003

R

MODEL1908210001

https://identifiers.org/biomodels.db:MODEL1908210001

R

MODEL1909050001

https://identifiers.org/biomodels.db:MODEL1909050001

RMC

MODEL1909050003

https://identifiers.org/biomodels.db:MODEL1909050003

RAH

MODEL1908290002

https://identifiers.org/biomodels.db:MODEL1908290002

RMC

MODEL1909060001

https://identifiers.org/biomodels.db:MODEL1909060001

RAH

MODEL1909030001

https://identifiers.org/biomodels.db:MODEL1909030001

RMC

MODEL1909180001

https://identifiers.org/biomodels.db:MODEL1909180001

RAH

MODEL1909090001

https://identifiers.org/biomodels.db:MODEL1909090001

R

MODEL1909120001

https://identifiers.org/biomodels.db:MODEL1909120001

R

MODEL1909110001

https://identifiers.org/biomodels.db:MODEL1909110001

R

MODEL1909160001

https://identifiers.org/biomodels.db:MODEL1909160001

R

MODEL1909170001

https://identifiers.org/biomodels.db:MODEL1909170001

RMC

MODEL1909170003

https://identifiers.org/biomodels.db:MODEL1909170003

R

MODEL1909250001

https://identifiers.org/biomodels.db:MODEL1909250001

R

MODEL1909180002

https://identifiers.org/biomodels.db:MODEL1909180002

RAH

MODEL1909230001

https://identifiers.org/biomodels.db:MODEL1909230001

R

MODEL1909170004

https://identifiers.org/biomodels.db:MODEL1909170004

R

MODEL1909240001

https://identifiers.org/biomodels.db:MODEL1909240001

R

MODEL1909240003

https://identifiers.org/biomodels.db:MODEL1909240003

R

MODEL1909250002

https://identifiers.org/biomodels.db:MODEL1909250002

RAH

MODEL1909250003

https://identifiers.org/biomodels.db:MODEL1909250003

R

MODEL1909270001

https://identifiers.org/biomodels.db:MODEL1909270001

R

MODEL1909260001

https://identifiers.org/biomodels.db:MODEL1909260001

R

MODEL1909260002

https://identifiers.org/biomodels.db:MODEL1909260002

R

MODEL1909300001

https://identifiers.org/biomodels.db:MODEL1909300001

R

MODEL1909300005

https://identifiers.org/biomodels.db:MODEL1909300005

RMC

MODEL1603110003

https://identifiers.org/biomodels.db:MODEL1603110003

RMC

MODEL1910020001

https://identifiers.org/biomodels.db:MODEL1910020001

RMC

MODEL1609100001

https://identifiers.org/biomodels.db:MODEL1609100001

R

MODEL1604100005

https://identifiers.org/biomodels.db:MODEL1604100005

RMC

MODEL7898438988

https://identifiers.org/biomodels.db:MODEL7898438988

RMC

MODEL1403250000

https://identifiers.org/biomodels.db:MODEL1403250000

R

MODEL1203070000

https://identifiers.org/biomodels.db:MODEL1203070000

RMC

MODEL1910250002

https://identifiers.org/biomodels.db:MODEL1910250002

R

MODEL1910290001

https://identifiers.org/biomodels.db:MODEL1910290001

R

MODEL1910290002

https://identifiers.org/biomodels.db:MODEL1910290002

R

MODEL1911010001

https://identifiers.org/biomodels.db:MODEL1911010001

R

MODEL1012080000

https://identifiers.org/biomodels.db:MODEL1012080000

R

MODEL1807160001

https://identifiers.org/biomodels.db:MODEL1807160001

R

MODEL1911100001

https://identifiers.org/biomodels.db:MODEL1911100001

R

MODEL1710230000

https://identifiers.org/biomodels.db:MODEL1710230000

R

MODEL1911100002

https://identifiers.org/biomodels.db:MODEL1911100002

R

MODEL1911100003

https://identifiers.org/biomodels.db:MODEL1911100003

R

MODEL1911110001

https://identifiers.org/biomodels.db:MODEL1911110001

R

MODEL1911100004

https://identifiers.org/biomodels.db:MODEL1911100004

R

MODEL1911120002

https://identifiers.org/biomodels.db:MODEL1911120002

R

MODEL1911120003

https://identifiers.org/biomodels.db:MODEL1911120003

R

MODEL1911120005

https://identifiers.org/biomodels.db:MODEL1911120005

R

MODEL1911120006

https://identifiers.org/biomodels.db:MODEL1911120006

R

MODEL1911130001

https://identifiers.org/biomodels.db:MODEL1911130001

R

MODEL1911130002

https://identifiers.org/biomodels.db:MODEL1911130002

R

MODEL1902140001

https://identifiers.org/biomodels.db:MODEL1902140001

R

MODEL1803220002

https://identifiers.org/biomodels.db:MODEL1803220002

R

MODEL1911130004

https://identifiers.org/biomodels.db:MODEL1911130004

R

MODEL1911140001

https://identifiers.org/biomodels.db:MODEL1911140001

R

MODEL1911130005

https://identifiers.org/biomodels.db:MODEL1911130005

R

MODEL1911130006

https://identifiers.org/biomodels.db:MODEL1911130006

R

MODEL1610100004

https://identifiers.org/biomodels.db:MODEL1610100004

R

MODEL1911140003

https://identifiers.org/biomodels.db:MODEL1911140003

R

MODEL1610100000

https://identifiers.org/biomodels.db:MODEL1610100000

R

MODEL1911180001

https://identifiers.org/biomodels.db:MODEL1911180001

R

MODEL1610100001

https://identifiers.org/biomodels.db:MODEL1610100001

R

MODEL1911180002

https://identifiers.org/biomodels.db:MODEL1911180002

R

MODEL1911270003

https://identifiers.org/biomodels.db:MODEL1911270003

R

MODEL1911270004

https://identifiers.org/biomodels.db:MODEL1911270004

R

MODEL1911280001

https://identifiers.org/biomodels.db:MODEL1911280001

R

MODEL1911280003

https://identifiers.org/biomodels.db:MODEL1911280003

R

MODEL1903280001

https://identifiers.org/biomodels.db:MODEL1903280001

R

MODEL1903280002

https://identifiers.org/biomodels.db:MODEL1903280002

R

MODEL1904020002

https://identifiers.org/biomodels.db:MODEL1904020002

R

MODEL1904020003

https://identifiers.org/biomodels.db:MODEL1904020003

R

MODEL1904030001

https://identifiers.org/biomodels.db:MODEL1904030001

R

MODEL1605030001

https://identifiers.org/biomodels.db:MODEL1605030001

R

MODEL1812070001

https://identifiers.org/biomodels.db:MODEL1812070001

R

MODEL1006230079

https://identifiers.org/biomodels.db:MODEL1006230079

R

MODEL8268650277

https://identifiers.org/biomodels.db:MODEL8268650277

R

MODEL1201140002

https://identifiers.org/biomodels.db:MODEL1201140002

R

MODEL1912020001

https://identifiers.org/biomodels.db:MODEL1912020001

R

MODEL1008060001

https://identifiers.org/biomodels.db:MODEL1008060001

R

MODEL1912040001

https://identifiers.org/biomodels.db:MODEL1912040001

RAH

MODEL1912100003

https://identifiers.org/biomodels.db:MODEL1912100003

R

MODEL1912120001

https://identifiers.org/biomodels.db:MODEL1912120001

R

MODEL1912120004

https://identifiers.org/biomodels.db:MODEL1912120004

R

MODEL1912160002

https://identifiers.org/biomodels.db:MODEL1912160002

R

MODEL1912160004

https://identifiers.org/biomodels.db:MODEL1912160004

R

MODEL1912160005

https://identifiers.org/biomodels.db:MODEL1912160005

RMC

MODEL1912170002

https://identifiers.org/biomodels.db:MODEL1912170002

R

MODEL1912170003

https://identifiers.org/biomodels.db:MODEL1912170003

R

MODEL1912090004

https://identifiers.org/biomodels.db:MODEL1912090004

R

MODEL1912130002

https://identifiers.org/biomodels.db:MODEL1912130002

RAH

MODEL1912100002

https://identifiers.org/biomodels.db:MODEL1912100002

R

MODEL1912100006

https://identifiers.org/biomodels.db:MODEL1912100006

R

MODEL1912130001

https://identifiers.org/biomodels.db:MODEL1912130001

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MODEL1912160003

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