Open Problems · Spring 2026

40 Open Research Problems
at the Frontier of ML + Science

Protein design. Drug discovery. Clinical AI. Formal mathematics.
All unsolved. All within reach.

Interested? I can supervise ML/computational aspects. For domain expertise, I'll connect you with the right co-mentor — Prof. Sandeep Juneja (CDLDS) for probability & optimization, biology faculty for wet-lab work, or other math/CS faculty. Email me at my Ashoka address with subject "IML: [Project ID]". All levels welcome — undergrad, master's, PhD.

Seven Research Domains

Protein &
Antibody Design

14 projects

Drug
Discovery

7 projects

Clinical AI &
Med Education

Your
Idea Here

propose one

B · Beginner
Y2 · 1 sem · 12 projects

→

I · Intermediate
Y3 · 1-2 sem · 15 projects

→

A · Advanced
Y4/Grad · 2 sem · 13 projects

Every project assumes basic Python + AI coding assistant. Projects tagged Juneja align with the Intro to ML course.

Beginner Projects

Y2 students · 1 semester · many Juneja-compatible

ID	Project	Domain	Key Prereqs	Tags
B1	Drug Repurposing for NAFLD/NASH	Drug Discovery	P&S	Juneja
B2	Cancer Drug Interaction Checker with Knowledge Graphs	Drug Discovery	Discrete Math
B3	Antibody Sequence Similarity Search with Edit Distance	Protein Design	DSA, P&S	Juneja
B4	Visualizing Protein Structure Prediction Confidence	Protein Design	Linear Algebra
B5	Monte Carlo Estimation of Protein Design Hit Rates	Protein Design	P&S	Juneja
B6	Classifying FDA Drug Labels with NLP	Clinical AI	Intro CS
B7	Medical Image Segmentation with Pre-trained Models	Medical Imaging	Linear Algebra
B8	Sequential Experimental Design for Antibody Campaigns	Protein Design	P&S	Juneja
B9	Molecular Property Prediction with TorchDrug	Drug Discovery	P&S	Juneja
B10	Simple Clinical Decision Support Rule Engine	Clinical AI	Intro CS
B11	Biomarker Identification for CVD Using Random Forests	Clinical AI	P&S	Juneja
B12	EDA of Antibody Design Campaign Results	Protein Design	P&S	Juneja

Intermediate Projects

Y3 students · 1-2 semesters · workshop paper potential

ID	Project	Domain	Key Prereqs	Origin
I1	Multi-Objective Optimization for Antibody Specificity	Protein Design	Real Analysis, P&S	Abhimanyu D1
I2	Metric Geometry of CDR Sequence Spaces	Protein Design	Metric Spaces	Abhimanyu D2
I3	Bayesian Optimization for Campaign Resource Allocation	Protein Design	P&S, Intro ML	Abhimanyu D5
I4	Persistent Homology of Protein Binding Interfaces	Protein Design / TDA	Algebra I	Abhimanyu D6
I5	Neuro-Symbolic Clinical Reasoning Prototype	Clinical AI	Intro ML, Logic	Ishaan D3
I6	Drug Discovery KG with Differentiable Reasoning	Drug Discovery	Intro ML, DSA	Ishaan D4
I7	Wasserstein Distances Between Antibody Repertoires	Protein Design / OT	Real Analysis, P&S	New
I8	GNN-Based Inverse Folding Analysis	Protein Design	Intro ML, Linear Algebra	New
I9	Information-Theoretic Scoring for Protein Design	Protein Design	P&S, Intro ML	New
I10	Monte Carlo Tree Search for Binder Design	Protein Design	P&S, DSA	Juneja
I11	ML-Driven Biomarker Discovery for NASH/NAFLD	Drug Discovery	P&S, Intro ML	New
I12	Convergence Analysis of Simplex Optimization	Optimization	Real Analysis, Linear Algebra	New
I13	AI-Augmented Tumor Board Extension	Medical Education	Intro ML	Onco-Shikshak
I14	Graph Diffusion for Oncology Hypothesis Generation	Drug Discovery	Intro ML, DSA	Onco-TTT
I15	Protein Design Competition Entry Pipeline	Protein Design	Intro ML	rfab-harness

Advanced Projects

Y4 / thesis / grad students · 2 semesters · publication-track

ID	Project	Domain	Key Prereqs	Origin
A1	GRPO Theory for Protein Diffusion Models	Protein Design	Measure Theory, Stat. Inference	Abhimanyu D3
A2	Exchangeable Arrays for PPI Prediction	Protein Design	Measure Theory, Random Graphs	Abhimanyu D4
A3	Formal Verification of Protein Designs via Lean4	Formal Math	Theory of Computation, Algebra II	Ishaan D1
A4	Proteins-as-Programs: Kolmogorov Complexity	Formal Math	Theory of Computation	Ishaan D2
A5	Categorical Deep Learning for Drug Discovery KGs	Neuro-Symbolic	Algebra II, Category Theory	Ishaan D4
A6	AI-Augmented Math Discovery for Biomedical Conjectures	Formal Math	Algebra II, Lean4	Ishaan D5
A7	Diffusion Models on SE(3) for Backbone Generation	Protein Design	Differential Geometry, DiffEq	New
A8	Geometric DL Expressivity for Protein Graphs	Protein Design	Algebra I, Linear Algebra	New
A9	Optimal Transport for Generative Model Evaluation	Math Foundations	Measure Theory, Functional Analysis	New
A10	Formally Verified Dual-Process Clinical Reasoning	Clinical AI	Logic, Theory of Computation	Ishaan D3
A11	Multi-Parameter Persistence for Protein Design Spaces	Math Foundations	Algebra II, Algebraic Topology	New
A12	Evolutionary Game Theory of Drug Resistance	Math Foundations	DiffEq, Game Theory	New
A13	RL with Experimental Feedback for Protein Design	Protein Design	Stat. Inference, Intro ML	New

Suggested Paths by Major

CS Major B6 or B10 → I5 or I8 → A3 or A10

Math Major B5 or B3 → I2 or I7 → A1 or A9

Bio + CS B1 or B9 → I11 or I14 → A12 or A13

Juneja Course B5 or B8 → I3 or I10 → A1 or A13

Getting Started

Tools: Protenix, Boltz-2, RFAntibody, DeepPurpose, TorchDrug, GUDHI, LeanDojo — all open-source
Textbooks: Boyd & Vandenberghe (Convex Optimization), Garnett (Bayesian Optimization), Bronstein (Geometric DL) — all free online
Competitions: Adaptyv Bio monthly challenges, BioML benchmark, ICLR GEM workshop
Communities: Lean4 Zulip, Adaptyv Discord, Ashoka KCDHA reading groups

Don't see your problem? Propose one.

If you have your own research question at the intersection of ML and science,
reach out — we'll find the right mentor combination.

Last updated March 2026. Full project details available on request.

40 Open Research Problemsat the Frontier of ML + Science