Privacy-Safe Curation Page

New Curation entry for in vivo CAR-T delivery intelligence. The page presents target-hypothesis context, internalized prior work, competitive benchmarks, technical literature, review-harness status and upgrade decisions without exposing raw source locations.

Operational Review Workbench

Curation now includes an interactive candidate review console and model lifecycle gate. Users can submit a neutral candidate intake, run the ICL/verification/panel harness, and check whether calibration, adapters, fine-tuning or retraining are allowed.

Candidate Review Harness

New pipeline/review/ package with CandidateIntake, Claim Ledger, ICL gate wrapper, verification gates and static multi-agent review panel. APIs: /api/v1/review/intake/validate, /icl-gate, /verify, /run, /eval/run.

Verification & Eval Gates

Hard gates now catch uncited material claims, predicted-as-measured language, target-finality overclaim, in vivo CAR-T delivery overclaim, weak benchmark context and duplicate-source double counting.

Model Lifecycle Readiness

New pipeline/model_lifecycle/ package and /api/v1/model-lifecycle/* endpoints. Blocks premature fine-tuning or retraining when sample size, endpoint consistency, split strategy, formulation metadata or calibration reports are insufficient.

Architecture v6

New architecture_overview_v6.md documents the decision architecture, privacy-safe curation rules, review harness, eval suite and model lifecycle gate.

Safety & Immunogenicity Assessment

New pipeline/safety/ module with 4-dimensional scoring: cytotoxicity (reactive groups, permanent charge), hepatotoxicity (biodegradability, CYP liability), hemolytic activity (amphiphilicity, charge density), immunogenicity (TLR motifs, complement activation). API: POST /api/v1/safety/assess.

Multi-Tissue Tropism Prediction

New pipeline/tropism/ module predicting organ selectivity (liver, spleen, lung, T-cell, DC) based on SORT mechanism (Cheng/Dilliard 2020-2021), pKa-driven charge ratio, PEG shielding, particle size, and tail saturation. Returns probability distribution + selectivity index. API: POST /api/v1/tropism/predict.

AGILE Fine-Tuning Infrastructure

Data preparation pipeline extracting 2,219 ICL-specific training samples from lipid_master.db (80/10/10 split). Fine-tuning script ready for GPU execution. Activity range: -2.35 to 15.96 log RLU across HeLa + Raw264 assays.

pKa Prediction v2

Replaced linear heuristic with RDKit-based model using LogP, TPSA, MW, Gasteiger partial charges, and EWG counting. Calibrated against SM-102 (6.44 vs 6.68), MC3 (6.61 vs 6.44), KC2 (6.61 vs 6.70). MAE reduced from ~1.3 to 0.32.

SISSO Feature Extraction — Validated

sisso_repro module fully functional: 22-dimensional geometric features from XZ/YZ density maps, 6 symbolic regression models (Model 7/8/9/12/15/17). All models reproduce within <5% RMSE of Lin et al. published results.

Lin 121 Conformation Data Import

Imported 121 lipid conformation records (XZ/YZ density map file paths), 121 transfection activity values (RLU), and 121 SISSO 22-dimensional feature vectors into descriptors table. Database: 1,338 lipids, 121 conformations.

Architecture v4 + Version Switcher

New architecture_overview_v4.md with closed-loop pipeline, pKa v2, SISSO, and deployment sections. Frontend version dropdown defaults to latest, preserves all previous versions (v1–v4).

JWT Auth Removal

Removed all JWT Bearer token references from frontend (agent, formulation, conjugation, validator, settings, mRNA pages). Platform uses HTTP Basic Auth exclusively.

Closed-Loop Seed Extraction

New API endpoint GET /exports/{run_id}/seeds extracts top-scored SMILES from completed runs. Pipeline page 'Seed from Previous Run' selector lets users load candidates from any prior run as seeds for the next iteration — closing the generate→score→seed loop.

Synthesis Candidate Triage

Results page now includes a 'Synthesis Candidates' section. Runs the 7-dimension validator on scored candidates and shows those graded B+ or above with composite score, predicted pKa, and synthesis action. Direct links to seed next run or inject wet-lab data.

Discovery Loop Visualization

Results page shows the full closed-loop flow: Score → Triage → Synthesize → Validate → Next Iteration. Each step links to the relevant platform action.

GCP Docker Deployment

Migrated from ECS to GCP VM (iaso-research-platform) with 3-service Docker stack (FastAPI API, Next.js frontend, nginx reverse proxy) on port 8090. System nginx proxies lnp.iaso-research.com with Let's Encrypt SSL.

FDA Reference Lipid Data

Seeded published activity data for SM-102, ALC-0315, DLin-MC3-DMA, DLin-KC2-DMA: pKa, particle size, PDI, encapsulation efficiency, zeta potential from Hassett 2019, Schoenmaker 2021, Jayaraman 2012, Semple 2010.

Science Audit Fixes

Chemical Space page: replaced mock SAR data with proper awaiting-data state. Library page: removed disabled enumerate button, show real reagent inventory. Basic auth user display in sidebar.

15-Page Smoke Test — All Pass

Complete page-by-page verification: Overview, Pipeline, Runs, Results, Formulation, mRNA, Conjugation, Iterations, Chemical Space, Library, Agent, Architecture, Settings, Login, 404. 0 TypeScript errors, 0 build warnings.

Library Endpoints

New GET /api/v1/library/stats and GET /api/v1/library/reagents endpoints. Queries lipid_master.db for real-time stats (1,216 lipids, ~4,600 activities). Previously returned 404.

CSV Upload Fix (Iterations)

Rewrote /inject-data from JSON body to multipart/form-data UploadFile. Frontend sends CSV via FormData — old endpoint returned 422 on every attempt. Critical for active learning loop.

CI/CD Deployment Pipeline

GitHub Actions workflow with IAP tunnel to GCP VM. SSH key-based deploy, docker-compose.prod.yml with localhost-only port binding, nginx reverse proxy with SSL.

Release Notes Page

This page — platform update documentation with feature descriptions, smoke test reports, and verification records for each release.

Next.js 15 Frontend

Complete migration from Streamlit to Next.js 15 + React 19 + Tailwind CSS 4. 15 pages with consistent design system, sidebar navigation, JWT authentication, and responsive layout.

TransMA Model Training

3D Transformer + Mamba architecture trained for lipid property prediction. Ensemble of 5 models for uncertainty quantification. CPU-only inference strategy for 16GB RAM.

AI Agent Chat

Claude-powered chat interface with thread persistence, suggested prompts, and markdown rendering. Integrated at /agent with animated gradient border effect.

Architecture Documentation

Comprehensive v3 architecture document served via API endpoint. TOC sidebar with intersection observer for scroll-tracking, collapsible sections, anchor navigation.

Formulation DOE Module

LNP formulation design-of-experiments with component percentage sliders, validation, prediction, and optimization suggestions.

mRNA Design Module

Protein-to-FASTA workflow with tissue selector, modification options, poly(A) configuration, quality metrics, and downloadable FASTA output.

5-Stage ML Pipeline

DAG-based pipeline: SISSO feature extraction → LSTM molecular generation → AGILE GNN screening (top 500) → RDKit ETKDG conformer generation → TransMA scoring (top 20).

External Model Integration

Integrated 4 external models: SISSO (Fortran, symbolic regression), AGILE (PyTorch GNN, 60k compound pretrained), TransMA (3D Transformer + Mamba), REINVENT4 (generative). Bootstrap script for automated setup.

FastAPI Backend

REST API with JWT authentication, run management (CRUD + progress + cancel/resume), exports (CSV/SDF), and system status monitoring.

SQLite Database

WAL-mode SQLite at lipid_db/lipid_master.db. Tables: lipids, activities, sources, conformations, iterations, iteration_results, users, settings, agent_plans, agent_threads.

Conda Environment

Reproducible icl-discovery conda env: Python 3.11, PyTorch CPU, PyTorch Geometric, RDKit, OpenBabel, gfortran, openmpi. Single environment.yml for all dependencies.