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# Human-GEM: The generic genome-scale metabolic model of _Homo sapiens_

[![Join the chat at https://gitter.im/SysBioChalmers/Human-GEM](https://badges.gitter.im/SysBioChalmers/Human-GEM.svg)](https://gitter.im/SysBioChalmers/Human-GEM?utm_source=badge&utm_medium=badge&utm_campaign=pr-badge&utm_content=badge) [![GitHub version](https://badge.fury.io/gh/sysbiochalmers%2FHuman-GEM.svg)](https://badge.fury.io/gh/sysbiochalmers%2FHuman-GEM)
[![DOI](https://zenodo.org/badge/105752644.svg)](https://zenodo.org/badge/latestdoi/105752644)<!-- ALL-CONTRIBUTORS-BADGE:START - Do not remove or modify this section -->
[![All Contributors](https://img.shields.io/badge/all_contributors-31-success.svg)](#contributors)
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### Brief Model Description

### Brief model description
This repository contains the latest version of Human-GEM, a human genome-scale metabolic model. We encourage [contributions](#contributing).

### Cite us:

If you use Human1 in your research, please cite:

> J. L. Robinson, P. Kocabasÿ, H. Wang, P.-E. Cholley, et al. An atlas of human metabolism. _Sci. Signal._ 13, eaaz1482 (2020). [doi:10.1126/scisignal.aaz1482](https://doi.org/10.1126/scisignal.aaz1482)
Starting from Human-GEM v1.5.0, all the releases are also archived in [Zenodo](https://doi.org/10.5281/zenodo.4099692) from which specific version can be cited if used.

If you use Mouse1, Rat1, Zebrafish1, Fruitfly1, or Worm1 in your research, please cite:

> H. Wang, J. L. Robinson, P. Kocabasÿ, J. Gustafsson, M. Anton, P.-E. Cholley, et al. Genome-scale metabolic network reconstruction of model animals as a platform for translational research. _PNAS_ 118, e2102344118 (2021). [doi.org/10.1073/pnas.2102344118](https://doi.org/10.1073/pnas.2102344118)


### Model Keywords

### Model keywords
**Utilisation:** predictive simulation, multi-omics integrative analysis, model template
**Field:** metabolic-network reconstruction
**Type of Model:** reconstruction, curated
Expand All @@ -34,38 +26,43 @@ If you use Mouse1, Rat1, Zebrafish1, Fruitfly1, or Worm1 in your research, pleas
**Metabolic System:** general metabolism
**Condition:** generic metabolism


### Model Overview

### Model overview
|Taxonomy | Template Model | Reactions | Metabolites| Genes |
| ------------- |:-------------:|:-------------:|:-------------:|:-----:|
|_Homo sapiens_ | HMR2, Recon3D, iHsa| {{nRXN}}| {{nMET}}| {{nGENE}}|


## Contributing

Contributions are always welcome! Read more about the project's philosophy in our [wiki](https://github.com/SysBioChalmers/Human-GEM/wiki) or have a look at the [Contributing guidelines](https://github.com/SysBioChalmers/Human-GEM/blob/main/.github/CONTRIBUTING.md) before starting.


## User Guide

## User guide
Detailed instructions on the installation and use of the Human-GEM model and repository can be found in the [Human-GEM user guide](https://sysbiochalmers.github.io/Human-GEM-guide/).

# Installation
## Required software
### Basic user
If you want to use the model for your own model simulations, you can use any software that accepts **SBML L3V1 FBCv3** formatted model files. This includes any of the following:

#### MATLAB-based
* [RAVEN Toolbox](https://github.com/SysBioChalmers/RAVEN) v2.10.3 or later (recommended, see [Installation instructions](https://github.com/SysBioChalmers/RAVEN/wiki/Installation#installation-instructions))
* [COBRA Toolbox](https://github.com/opencobra/cobratoolbox)

## Installation
#### Python-based
* [cobrapy](https://github.com/opencobra/cobrapy)

### Required Software
* A functional MATLAB installation (MATLAB 7.3 and higher).
* The [RAVEN toolbox](https://github.com/SysBioChalmers/RAVEN).
* The [COBRA toolbox](https://github.com/opencobra/cobratoolbox) (not necessary for most functionality).
Please see the installation instructions for each software package.

### Developer
#### MATLAB-based
If you want to contribute to the development of Human-GEM, or otherwise want to run any of the [provided](https://github.com/SysBioChalmers/Human-GEM/tree/main/code) MATLAB functions, then the following software is required:
* [RAVEN Toolbox](https://github.com/SysBioChalmers/RAVEN) v2.10.3 or later (recommended, see [Installation instructions](https://github.com/SysBioChalmers/RAVEN/wiki/Installation#installation-instructions))

### Dependencies - Recommended Software
* The libSBML MATLAB API (version [5.13.0](https://sourceforge.net/projects/sbml/files/libsbml/5.13.0/stable/MATLAB%20interface/) is recommended).
* [Gurobi Optimizer](http://www.gurobi.com/registration/download-reg) for any simulations.
#### Python-based
You can also contribution to the development of Human-GEM via python (e.g. cobrapy), even if you would not be able to run any of the model-specific MATLAB functions. To curate the model, you can still edit `Human-GEM.yml`, `genes.tsv`, `metabolites.tsv` and `reactions.tsv`, all located in the `model/` folder.

### Recommended solver
* When performing simulations with Human-GEM, you are encouraged to use [Gurobi Optimizer](https://www.gurobi.com/academia/academic-program-and-licenses/).

### Installation Instructions
## Installation instructions
* Clone the [main branch](https://github.com/SysBioChalmers/Human-GEM/tree/main) of this repository, or [download the latest release](https://github.com/SysBioChalmers/Human-GEM/releases/latest).
* Add the directory to your MATLAB path either by using the lines below or manually (instructions [here](https://se.mathworks.com/help/matlab/ref/addpath.html?requestedDomain=www.mathworks.com)).
```matlab
Expand All @@ -77,47 +74,35 @@ HumanGEMInstaller.install
HumanGEMInstaller.uninstall
```

## Model Files

The model is available as `.xml`, `.xlsx`, `.txt`, `.yml`, and `.mat` in the `model/` directory. Note that only the `.yml` version is available on branches other than `main` (e.g., `develop`), to facilitate tracking of model changes.
## Model files
The model is available as `.xml`, `.xlsx`, `.txt`, `.yml`, and `.mat` in the `model/` directory.

The model development is based on the `yml` file (to facilitate tracking of model changes), so that this is the only model format available on non-`main` branches (such as `develop`). See also the [location of annotation information](#reaction-metabolite-and-gene-annotations).

## Usage

#### Loading/saving the model

`Human-GEM.mat` (Recommended if on `main` branch)
#### Loading/saving the model in MATLAB
`Human-GEM.mat` (Recommended if on `main` branch):
* Load and save using the built-in MATLAB `load()` and `save()` functions.

`Human-GEM.yml` (Recommended if on `develop` or other branches)
* Load using the `importYaml.m` function (in `code/io/`)
* Save using the `exportYaml.m` function (in `code/io/`)

`Human-GEM.xml` (SBML format)
* Load using the `importModel.m` function (from [RAVEN Toolbox](https://github.com/SysBioChalmers/RAVEN))
* Save using the `exportModel.m` function (from [RAVEN Toolbox](https://github.com/SysBioChalmers/RAVEN))


## Reaction, Metabolite, and Gene Annotations

Additional annotation information and external identifiers for Human-GEM reactions, metabolites, and genes are provided as `tsv` files in the `model/` directory (`reactions.tsv`, `metabolites.tsv`, and `genes.tsv`, respectively).
`Human-GEM.yml` (Recommended if on `develop` or other branches):
* Load using the `readYAMLmodel.m` function (from [RAVEN Toolbox](https://github.com/SysBioChalmers/RAVEN)).
* Save using the `writeYAMLmodel.m` function (from [RAVEN Toolbox](https://github.com/SysBioChalmers/RAVEN)).

To import/export this annotation data to/from MATLAB, use the `importTsvFile` and `exportTsvFile` functions, respectively.
`Human-GEM.xml` (SBML format):
* Load using the `importModel.m` function (from [RAVEN Toolbox](https://github.com/SysBioChalmers/RAVEN)).
* Save using the `exportModel.m` function (from [RAVEN Toolbox](https://github.com/SysBioChalmers/RAVEN)).

## Reaction, metabolite, and gene annotations
By default, additional annotation information and external identifiers for Human-GEM reactions, metabolites, and genes are **not** kept in the `yml` file, but rather provided as `tsv` files in the `model/` directory (`reactions.tsv`, `metabolites.tsv`, and `genes.tsv`, respectively). The `annotateGEM` function can add those annotations in MATLAB, while direct import/export of this annotation data is done through the `importTsvFile` and `exportTsvFile` functions, respectively.

## Websites

- [Metabolic Atlas](https://metabolicatlas.org/) enables visualization and exploration of Human-GEM content.
- The [Human-GEM user guide](https://sysbiochalmers.github.io/Human-GEM-guide/) provides detailed instructions and examples for using the Human-GEM model and repository.


## Metabolic Maps

## Metabolic maps
A collection of manually curated 2D metabolic maps associated with Human-GEM are stored in the [Human-maps repository](https://github.com/SysBioChalmers/Human-maps). These maps can be downloaded from the repository or explored interactively using [Metabolic Atlas](https://metabolicatlas.org/explore/map-viewer/human1).


## Contributors

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