MHCXGraph 0.1.1

A python package for graph-based detection of structurally similar surface regions in protein complexes, with a focus on peptide-MHC (pMHC) systems involved in T cell receptor (TCR) recognition.

MHCXGraph

A Python package for detecting potential T cell receptor cross-reactivity based on peptide–MHC structures.

MHCXGraph leverages graph-based approaches to identify conserved exposed regions across multiple pMHC structures. It supports multiple execution modes and offers fully adjustable parameters, enabling flexible configuration to suit diverse user needs. For result analysis, the package provides an interactive dashboard that facilitates data exploration through graph visualizations and projections onto 3D structures

See also:

• Documentation
• GitHub repository

Installation

From PyPI (stable): To install the latest release on PyPI, run:

pip install MHCXGraph

From source (development):

git clone https://github.com/cnpem/MHCXGraph.git
pip install -e MHCXGraph

Quick Start

MHCXGraph is configured via a JSON manifest file. An example is in examples/manifests/manifest-minimal.json. To run it:

MHCXGraph run examples/manifests/manifest-minimal.json

A basic manifest has the following structure:

{
  "settings": {
    "run_name": "my-run",
    "run_mode": "multiple",
    "output_path": "path/to/output/",
    "edge_threshold": 8.5,
    "node_granularity": "all_atoms",
    "triad_rsa": false,
    "rsa_filter": 0.1,
    "global_distance_diff_threshold":2.0,
    "local_distance_diff_threshold":1.0,
    "distance_bin_width": 2,
  },
  "inputs": [
    {
      "path": "path/to/input",
      "extensions": [".pdb", ".cif"],
      "selectors": [{ "name": "MHC1" }]
    }
  ],
  "selectors": {
    "MHC1": {
      "chains": ["C"],
      "structures": {},
      "residues": {
        "A": [18,19,42,43,44,54,55,56,58,59,61,62,63,64,65,66,68,69,70,71,72,73,75,76,79,
            80,83,84,89,108,109,142,143,145,146,147,148,149,150,151,152,153,154,155,156,
            157,158,159,161,162,163,165,166,167,169,170,171]
      }
    },
    ,
    "MHC2": {
      "chains": ["C"],
      "residues": {
        "A": [37,51,52,53,55,56,58,59,60,62,63,65,66,67,69],
        "B": [56,57,59,60,61,62,63,65,66,67,68,69,70,71,72,73,74,77,78,81]
      }
    },
    "general": {
	    "chains" : ["C"],
	    "structures" : ["helix"],
	    "residues" : {}
    }
  }
}

[!WARNING] Input structures in this example have been pre-processed with MHCXGraph renumber. This step must be executed before graph analysis whenever residue selectors targeting TCR-contacting positions are used.

Key Configuration Parameters¹

Category	Parameter	Description	Default
Execution	run_name	Name of the run	test
	run_mode	Execution mode: pairwise, multiple, or screening	multiple
	output_path	Path for results output	./outputs
	reference_structure	Path to reference structure (required for screening mode)	None
Graph	node_granularity	Atomic representation for residue nodes: ca_only, all_atoms, backbone, or sidechain	all_atoms
	edge_threshold	Distance cutoff (Å) for defining edges between nodes	8.5
	include_ligands	Include ligands as graph nodes	true
	include_noncanonical_residues	Include modified amino acids as nodes	true
	include_waters	Include water molecules as nodes	true
	filter_triads_by_chain	Restrict triads to those with at least one node from the specified chain	None
	max_gap_helix	Max residue gap between helices to treat them as continuous	0
Triad comparison	distance_bin_width	Width of distance bins for discretization	2.0
	local_distance_diff_threshold	Max distance difference (d1/d2/d3) between triads for association	1.0
	global_distance_diff_threshold	Max distance difference between non-adjacent nodes across structures (frame generation step)	2.0
	close_tolerance	Tolerance for placing distances at bin center	0.1
Surface representation	rsa_filter	Min RSA for canonical residues to be included as nodes	0.1
	asa_filter	Min ASA for non-canonical residues, waters, and ligands	5
RSA tokens ²	triad_rsa	Use RSA values in triad token representation	false
	rsa_bin_width	Width of RSA bins for discretization	0.3
	rsa_diff_threshold	Max RSA difference between triad nodes for association	0.3
	close_tolerance_rsa	Tolerance for placing RSA values at bin center	0.01

¹ A complete description of all parameters can be found in the documentation

² RSA token parameters are only active when triad_rsa: true.

Selectors

Selectors define which residues and chains are included as graph nodes. They can be specified by chain ID, residue index, or secondary structure type (helix, etc.), and referenced by name in the inputs block.

Citation

• (manuscript in preparation)

License

The software is licensed under the terms of the GNU Affero General Public License 3 (AGPL3) and is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU Affero General Public License for more details.