Harshini Suresha

RNA Therapeutic-Design Platform

Mechanism Arbitration and Candidate Generation Across Nine Therapeutic Goals

Year2026
LocationNCBS
TagsASO, siRNA, SpliceAI, ViennaRNA

A single-pass pipeline arbitrating across 41 RNA therapeutic mechanisms & 9 goals, with 19 mechanism-specific features (SpliceAI, RNAplfold, miRNA, RBP sites), benchmarked on 165,237 rows and 7 ML models across 12 experiments.

Jun 2026 – Sep 2026 at NCBS, Bangalore, supervised by Dr. Tanay Bhatt.

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Figure for RNA Therapeutic-Design Platform: Mechanism Arbitration and Candidate Generation Across Nine Therapeutic Goals
Methods
  1. 01
    Mechanism arbitration

    A single-pass pipeline that, for a therapeutic goal, weighs 41 RNA therapeutic mechanisms across 9 goals and decides which ones apply before designing anything.

    Python, Mechanism-arbitration API
  2. 02
    Target & transcript validation

    Resolved genes and transcripts per organism from reference annotation, with provenance tracking, confidence caps and explicit Unresolved / Not-applicable states so the pipeline never over-claims.

    Ensembl, NCBI, Genome-scale reference data
  3. 03
    Mechanism-specific features

    Built 19 features covering splice prediction, RNA accessibility, miRNA targeting, promoter accessibility, RNA-binding protein sites, alternative polyadenylation, promoter switching and intron retention, then scored and ranked candidate oligos.

    SpliceAI, ViennaRNA RNAplfold, miRNA targeting, RBP sites
  4. 04
    Benchmarking

    Analysed 165,237 benchmark rows across RNase H (159,109), splice-switching (2,181) and siRNA (3,947) modalities to compare mechanism-specific performance.

    Pandas, Benchmark datasets
  5. 05
    Machine-learning experiments

    Evaluated seven ML models across 12 controlled experiments: class imbalance, gene-grouped splitting, ranking, cross-chemistry transfer, feature attribution, thermodynamics, RNA-FM embeddings and ML versus heuristics.

    Scikit-learn, RNA-FM, Feature attribution
  6. 06
    Testing

    Validated the API and workflow with 84 mechanism-arbitration tests and 11 feature-level tests, including regression tests for defects found along the way.

    pytest, Regression testing
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