Mycobacterial Metabolic Model Development for Drug Target Identification
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Editor’s Assessment
This work has generated metabolic models for the human pathogens Mycobacterium leprae and Mycobacteroides abscessus, alongside a new computational tool that can be used to identify potential drug targets. The standardised genomic scale metabolic models have been developed using the systems biology community standards for quality control and evaluation of models. After providing more detail on reproducibility, comparative performance of the models, and reuse, these resources are now published and are available for reuse by the global scientific community via the GigaDB, Biomodels, and PatMeDB repositories.
This assessment refers to version 1 of this preprint.
This article has been Reviewed by the following groups
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- Evaluated articles (GigaByte)
- Endorsed by GigaByte (scotted400)
Abstract
Antibiotic resistance is increasing at an alarming rate, and three related mycobacteria are the source of widespread infections in humans. According to the World Health Organization, Mycobacterium leprae , which causes leprosy, is still endemic in tropical countries; Mycobacterium tuberculosis is the second largest infectious disease killer worldwide after COVID-19; Mycobacteroides abscessus , a group of non-tuberculous mycobacteria, causes lung infections and other health-care-associated infections in humans. Due to the rise in resistance to common antibacterial drugs, it is critical to develop alternatives to traditional treatment procedures. Furthermore, an understanding of the biochemical mechanisms underlying pathogenic evolution is important for the treatment and management of these diseased conditions.
In this study, metabolic models have been developed for two bacterial pathogens, M. leprae , and M. abscessus , and a new computational tool has been used to identify potential drug targets, which are referred to as bottleneck reactions. The genes, reactions, and pathways in each of these organisms have been highlighted; the potential drug targets can be further explored as broad-spectrum antibacterials and the unique drug targets to each pathogen are significant for precision medicine initiatives.
The models and associating datasets are available in GigaScience and the following repositories:
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M. abscessus
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Biomodels: https://www.ebi.ac.uk/biomodels/MODEL2203300002
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https://www.patmedb.org/Bacteria/Mabscessus
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M. leprae
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Biomodels: https://www.ebi.ac.uk/biomodels/MODEL2203300001
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https://www.patmedb.org/Bacteria/Mleprae
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Article activity feed
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Editor’s Assessment
This work has generated metabolic models for the human pathogens Mycobacterium leprae and Mycobacteroides abscessus, alongside a new computational tool that can be used to identify potential drug targets. The standardised genomic scale metabolic models have been developed using the systems biology community standards for quality control and evaluation of models. After providing more detail on reproducibility, comparative performance of the models, and reuse, these resources are now published and are available for reuse by the global scientific community via the GigaDB, Biomodels, and PatMeDB repositories.
This assessment refers to version 1 of this preprint.
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ABSTRACT
This work has been published in GigaByte Journal under a CC-BY 4.0 license (https://doi.org/10.46471/gigabyte.80), and has published the reviews under the same license. These are as follows.
**Reviewer 1. Grace Mugumbate **
Please add additional comments on language quality to clarify if needed
Yes. First person reporting has been used with the word "We' used extensively.
Are the data and metadata consistent with relevant minimum information or reporting standards?
No. There is need to specify the type, size, standardisation and curation of the data that was used, especially when additional data was obtained from different databases.
Is the data acquisition clear, complete and methodologically sound?
Yes. Sources of data are indicated in the paper, however the size of the data sets and type of data is not clear.
Is there …
ABSTRACT
This work has been published in GigaByte Journal under a CC-BY 4.0 license (https://doi.org/10.46471/gigabyte.80), and has published the reviews under the same license. These are as follows.
**Reviewer 1. Grace Mugumbate **
Please add additional comments on language quality to clarify if needed
Yes. First person reporting has been used with the word "We' used extensively.
Are the data and metadata consistent with relevant minimum information or reporting standards?
No. There is need to specify the type, size, standardisation and curation of the data that was used, especially when additional data was obtained from different databases.
Is the data acquisition clear, complete and methodologically sound?
Yes. Sources of data are indicated in the paper, however the size of the data sets and type of data is not clear.
Is there sufficient detail in the methods and data-processing steps to allow reproduction?
No. There is need to give more detail in the methods for reproducibility.
Is there sufficient data validation and statistical analyses of data quality?
No. Validation was performed, however no statistical analyses was mentioned.
Is there sufficient information for others to reuse this dataset or integrate it with other data?
No. More detail is needed on data retrieval to allow reuse of the dataset.
Additional Comments:
The Authors presented their work entitled 'Mycobacterial Metabolic Model Development for Drug Target Identification'. This is very innovative work that led to generation of M. laprae and M. abscessus models, important tools for drug target identification. Target identification for a number of infectious diseases provides information for structure-based molecular modification of new and alternative diseases. The target specific compounds will help reduce side effects among other things. Generation of the models by the authors is commendable.There are a few corrections:
- Under Abstract: Line 4: Please note that Mycobacterium tuberculosis is not a disease but the bacterium that causes the diseases tuberculosis.
- Mehtods, GEM reconstruction, curation and simulation (i) Line two: Name the "other organism specific databases" (ii) Give a brief description of the COBRApy and the GLPK even if the source had been given.
- The Method section need to be more informative to allow for reproducibility.
**Reviewer 2. Nagasuma Chandra **
Is there sufficient detail in the methods and data-processing steps to allow reproduction?
Yes. It would be useful if the authors could comment on how the models vary between the two species and with respect to M. tuberculosis. Specifically, a note on how the authors deal with alternate enzymes and whether they included enzymes specific to each species, would be helpful.
Is the validation suitable for this type of data?
Yes. A figure depicting the overall capability of the models would be useful
Additional Comments:
Genome-scale metabolic models are useful to the community as they can be used to address a variety of questions. It would be useful if the authors could include a section on the comparative performance of the models and link it to the known metabolic capability of these microbes.
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