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Explore real-world applications across clinical validation, target discovery, and drug development

Clinical ApplicationOngoingBreast Cancer

Hidden Subtype Detection in Breast Cancer

Revealing Misdiagnosed Cancer Populations at Single-Cell Resolution

Discovered hidden cancer subtypes missed by traditional bulk diagnostics. Found ER+ cells in TNBC-diagnosed patients and TNBC cells in ER+-diagnosed patients, preventing inappropriate treatment selection.

Key Findings

  • Detected ER+ subclusters within TNBC-diagnosed tumors
  • Identified TNBC populations in ER+-diagnosed patients
  • Confirmed findings through biomarker validation
  • Explained treatment resistance and recurrence patterns

Methodology

  • 1Single-cell RNA sequencing analysis
  • 2AI-powered subtype classification
  • 3Biomarker expression validation
  • 4Comparison with bulk diagnostic results

Results

  • Revealed false negatives in traditional diagnostics
  • Identified patients at risk of treatment failure
  • Enabled more precise treatment selection

Clinical Impact

Prevents inappropriate treatment by detecting hidden subtypes, reducing therapy failure and recurrence risk through accurate patient stratification.

Clinical ApplicationOngoingHER2+ Breast Cancer

The Hidden Enemy in HER2+ Breast Cancer

Identifying Pre-Existing Resistant Clones (TOP2A+/RAD21+) Invisible to Traditional Profiling

Identified pre-existing drug-resistant cancer cell populations (TOP2A+/RAD21+) in treatment-naïve HER2+ breast cancer patients that are invisible to traditional bulk sequencing methods. T-DXd resistance isn't just acquired—it's often waiting there before treatment begins.

Key Findings

  • Discovered TOP2A+/RAD21+ resistant cell populations in untreated patients
  • T-DXd resistance exists before treatment initiation, not just acquired
  • Current bulk-seq tools cannot detect these rare resistant cells
  • Enhanced DNA repair mechanisms drive drug resistance in specific cells
  • Resistant cells exhibit distinct cell cycle control and drug resistance patterns

Methodology

  • 1Single-cell RNA sequencing of treatment-naïve HER2+ samples
  • 2TOP2A and RAD21 expression profiling at cellular resolution
  • 3DNA repair pathway enrichment analysis
  • 4Gene regulatory network (GRN) analysis (TFDP1/E2F regulons)
  • 5Comparison with bulk RNA-seq sensitivity limitations
  • 6B2SC-based HER2+ cluster prediction and validation

Results

  • Pre-existing resistant clones identified across multiple untreated patients
  • TOP2A regulon activity significantly elevated in resistant populations
  • TFDP1/E2F pathway enrichment confirmed in resistant clones
  • Predictive biomarkers for T-DXd treatment response established
  • B2SC successfully predicted and validated HER2+ related clusters
  • Potential synergistic agents with T-DXd identified for resistant clones

Clinical Impact

Enables pre-treatment identification of patients likely to develop T-DXd resistance, allowing personalized therapy selection before resistance emerges.

Clinical ApplicationOngoingBreast Cancer

Mechanism-Based Patient Stratification

Beyond Expression: Identifying Functionally Active Targets

Distinguished between high expression and high functional activity using Gene Regulatory Network analysis. Eliminates false positive targets by confirming which pathways are actually driving disease.

Key Findings

  • Identified functionally active regulatory networks
  • Distinguished passenger from driver molecular changes
  • Mapped differential pathway activity across subtypes
  • Validated mechanistic link to disease progression

Methodology

  • 1Gene Regulatory Network (GRN) inference
  • 2Transcription factor activity quantification
  • 3Single-cell pathway analysis
  • 4Functional validation of target activity

Results

  • Confirmed drug targets with functional activity
  • Eliminated false positive stratification markers
  • Enabled mechanism-based patient selection

Clinical Impact

Reduces clinical trial failures by ensuring treatments target functionally active pathways, not just highly expressed genes.

Target DiscoveryCompletedPDACHGSOCSCLC

bsADC Target Identification

Bispecific ADC Target Discovery

Identified validated druggable gene pairs across cancer subtypes with minimal off-tumor toxicity.

Key Findings

  • Discovered 6+ validated gene pairs across multiple cancers
  • Achieved cancer cell specificity with low toxicity risk
  • Validated through wet lab experiments

Methodology

  • 1Single-cell gene expression analysis
  • 2Cancer specificity simulation
  • 3Toxicity validation against healthy organs

Clinical Impact

Enabled rapid bsADC program advancement with validated, cancer-specific targets.

Drug DevelopmentCompletedBreast Cancer

CDK-inhibitor MoA Analysis

Pathway Understanding in Breast Cancer

Identified transcription factors regulating CDK-inhibitor expression through regulatory network analysis.

Key Findings

  • Mapped complete regulatory landscape
  • Identified novel regulatory candidates
  • Characterized differential activity patterns

Methodology

  • 1Gene Regulatory Network inference
  • 2Single-cell regulon quantification
  • 3Pathway analysis

Clinical Impact

Provided mechanistic insights for therapeutic intervention targeting.

Drug DevelopmentCompletedMultiple

PROTAC E3 Ligase Optimization

Cell-Type Specific Ligase Selection

Optimized E3 ligase selection at cellular resolution for PROTAC development.

Key Findings

  • Profiled cell-type specific E3 ligase expression
  • Identified optimal ligase-target pairs

Methodology

  • 1Single-cell E3 ligase profiling
  • 2Cell-type specific expression analysis

Clinical Impact

Enables rational PROTAC design with improved degradation efficiency.

Drug DevelopmentCompletedMultiple

ICI Response Biomarkers

T-cell Trajectory Analysis

Mapped T-cell trajectories to identify immune checkpoint inhibitor response biomarkers.

Key Findings

  • Mapped T-cell activation to exhaustion trajectory
  • Identified novel biomarker candidates

Methodology

  • 1Pseudotime trajectory analysis
  • 2TME profiling

Clinical Impact

Provides predictive biomarkers for better patient selection.

Drug DevelopmentCompletedNSCLC

TKI Resistance Mechanisms

Resistance Pathway Analysis

Decoded cellular heterogeneity in TKI response to identify resistance mechanisms.

Key Findings

  • Mapped alternative resistance pathways
  • Identified combination therapy targets

Methodology

  • 1In-silico drug perturbation
  • 2Pathway activation analysis

Clinical Impact

Guides combination therapy design to overcome resistance.

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