Datasets from Multi-omic characterization of the ILC Cell Line Encyclopedia (ICLE)

This repository contains the processed multi-omic datasets and supplementary material for the ILC Cell Line Encyclopedia (ICLE).

Dataset Overview The ICLE provides a comprehensive molecular characterization of Invasive Lobular Carcinoma (ILC) and ILC-like breast cancer cell lines. This deposition includes processed data files supporting the manuscript: "Multi-omic characterization of the ILC cell line encyclopedia (ICLE) defines new models for biomarkers discovery and therapeutic exploration."

1. ICLE Datasets (Internal) This section contains processed data generated specifically for this study, organized by platform:

Optical Genome Mapping (Bionano): Contains structural variation (SV) calls, gene fusion candidates, and ShatterSeek output for chromothripsis analysis.

SNP Arrays (CytoSNP): Includes raw IDAT files, processed genotyping data, and copy number segmentation files. Analyses include GISTIC2.0 output, chromosomal instability (CIN) metrics, and CNTools logRR matrices.

DNA Methylation (DNAm): Processed beta-value matrices derived from Illumina arrays (processed via SeSAMe), including differential methylation results (Limma) comparing ILC vs. NST subtypes.

Transcriptomics (RNA-seq): Gene expression data including raw counts, normalized log2CPM values, and PAM50 molecular subtyping scores. Differential expression analysis (DESeq2) results are provided for various comparisons.

Proteomics (RPPA): Normalized protein expression matrices from Reverse Phase Protein Arrays (RPPA), including batch-corrected data (COMBAT) and antibody mapping files.

Whole Exome Sequencing (WES): Variant calling files (VCF), filtered Mutation Annotation Files (MAF), Tumor Mutational Burden (TMB) calculations, and specific read pileups for CDH1 analysis.

Note: Raw RNAseq and WES sequencing files are available at BioProject PRJNA1406296.

2. External Datasets (Benchmarking & Integration) We integrated and analyzed public datasets from the following sources. Processed extracts relevant to this study are included in the External/ directory:

BRCA Cell Line References: Broad Institute CCLE, Sanger Institute (COSMIC/GDSC), and Marcotte et al. datasets.

BRCA Patient Cohorts: TCGA, MSK-IMPACT, and FMI (Foundation Medicine) clinical genomic profiles.

Analysis Code: All scripts for figure generation and processing are available on GitHub. To reproduce the analyses of this study, clone the GitHub repository as well as download the content from this zenodo repository and place in 1-Dataset (folder in GitHub repository).

cBioPortal Instance: cBioPortal instances were setup for ICLE and Integrated BRCA cell line datasets for visualization and analysis.

Authors Osama Shiraz Shah, Fangyuan Chen, Abdalla Wedn, Anokhi Kashiparekh, Beth A. Knapick, Jian Chen, Laura Savariau, Ben Clifford, Matthias Christgen, Ethan Sokol, Jagmohan Hooda, Jennifer M. Atkinson, Steffi Oesterreich*, Adrian V. Lee* *Equal contribution, corresponding authors