ATLANTiC

ATLANTiC analyzes proteome activity landscapes of cancer cell lines to elucidate molecular mechanisms underlying drug responses and predict drug sensitivity.

Key Features:

• Comprehensive Data Integration: Integrates quantitative genome, transcriptome, and proteome data, including measurements of 10,000 proteins and 55,000 phosphorylation sites (p-sites) across 125 cancer cell lines (CCLs).
• Proteome Activity Landscapes: Maps proteome activity landscapes to contextualize proteins and p-sites within cellular networks and enable prediction of drug sensitivity based on phosphorylation events.
• Functional Associations and Predictions: Identifies functional associations between protein activities and drug responses, exemplified by Progesterone Receptor (PGR) phosphorylation linked to sensitivity to estrogen signaling modulators such as Raloxifene, and by Adenylate kinase isoenzyme 1 (AK1) inactivating antimetabolites like Cytarabine with correlated poor survival in acute myeloid leukemia patients treated with Cytarabine.
• Stratification and Target Identification: Supports identification of molecular markers (e.g., AK1) for patient stratification and prioritization of potential drug targets.

Scientific Applications:

• Drug sensitivity and resistance analysis: Investigate molecular bases of drug sensitivity and resistance using integrated genome, transcriptome, proteome, and p-site data.
• Biomarker discovery: Identify biomarkers for patient stratification and therapeutic targeting, including phosphorylation-based markers.
• Therapeutic hypothesis generation: Explore and prioritize novel drug combinations and treatment strategies informed by proteome activity landscapes.

Methodology:

Integrates quantitative genome, transcriptome, and proteome measurements; maps proteome activity landscapes; performs association analyses linking protein and phosphorylation-site activity to drug responses; and predicts drug sensitivity and stratification markers.