LungTCR - TCR Repertoire Analysis and Lung Cancer Prediction

Overview

LungTCR (https://www.lungtcr.com/) is a comprehensive website for analyzing T-cell receptor (TCR) repertoire data with specialized functions for cancer risk assessment. This repository contains:

• TCR repertoire feature calculation pipeline
• Cancer-associated TCR enrichment scoring
• Machine learning models for lung cancer/malignant pulmonary nodule risk prediction

Key Features

Feature	Description
TCR Repertoire Analysis	Calculates 20+ diversity and clonality metrics
Cancer TCR Enrichment	Quantifies tumor-associated TCR signatures
Risk Prediction Models	Random Forest/GBM models for lung cancer risk assessment
Visualization	Plotting of key TCR features and model result

Input File Format

The input file format is VDJtools' table format. Run Convert routine by VDJtools (https://vdjtools-doc.readthedocs.io/en/master/input.html#vdjtools-format) to geneate the format.

Clonotype Table Requirements

Column	Required	Description	Example
count	Yes	Read counts of TCR clones	161853
freq	Yes	Frequency of TCR clones	0.009385
cdr3_nt	Yes	CDR3 nucleic acid sequence	TGTGCCAGTTCGTCGTCTAGCTCCTACAATGAGCAGTTCTTC
cdr3_aa	Yes	CDR3 amino acid sequence	CASSSSSSYNEQFF
v	Yes	V gene segment	TRBV6-4
d	Yes	D gene segment	.
j	Yes	J gene segment	TRBJ2-7
VEnd	No	Position of the V gene end	7
Dstart	No	Position of the d gene start	.
Dend	No	Position of the D gene end	.
Jstart	No	Position of the J gene strat	18
sample_id	No	Sample identifier	Patient01_PBMC

Example file (tabular format):

count	freq	cdr3nt	cdr3aa	v	d	j	VEnd	DStart	DEnd	JStart
161853	0.009385105218213133	TGTGCCAGTTCGTCGTCTAGCTCCTACAATGAGCAGTTCTTC	CASSSSSSYNEQFF	TRBV6-4	.	TRBJ2-1	7	-1	-1	18
128851	0.007471472215355789	TGTGCCAGCTCACCATAGGACAGTGCTTCTCTGGAAACACCATATATTTT	CASSP*DS_FSGNTIYF	TRBV18	TRBD1	TRBJ1-3	14	17	22	28
107730	0.006246763329429179	TGTGCCAGCAGTTACGGTCTAAGAGATACGCAGTATTTT	CASSYGLRDTQYF	TRBV6-5	.	TRBJ2-3	14	-1	-1	23
...

Basic Usage

python TCRfeatureCal.py -m /extdata/metadata.tsv -o output_features/
python diversity_vdjtools_wrapper.py -m /extdata/metadata.txt -o outout_diversity/ -x 10000000
Rscript LungTCR_ModelPrediction.R -i /extdata/test.csv -o output_model/ -m /model/models_list.rds -f /model/SelectedFeatures.csv 

Output includes:

• Diversity indices (Shannon, Simpson, etc.)
• Clonality metrics
• V/J gene usage profiles
• CDR3 length distributions
• CDR3 amino acid compositions
• TCR clones frequency distributions
• TCR convergence index
• Lung cancer enrichment score
• Lung cancer prediction result

Citation

The code files here are linked to the work "Large-Scale TCR Repertoire Profiling Unveils Tumor-Specific Signals for Diagnosing Indeterminate Pulmonary Nodules" by Chen et al .