v1.2.0 - Thermodynamic QC Fix, RAA Exo-Probe Architecture & Scientific Standardization

What's New in v1.2.0

🐛 Critical Thermodynamic Fixes

• ΔG Unit Normalization: Fixed unit mismatch in reranking.py where raw primer3-py ThermoAnalysis outputs (cal/mol) were compared directly against kcal/mol thresholds, ensuring precise thermodynamic filtering.
• Two-Stage Re-ranking: Fully enabled multi-candidate ranking and QC filtering across PCR, qPCR, and RAA workflows.

🧬 RAA Exo-Probe Architecture

• Automated Abasic (THF) Placement: Programmatic constraint-satisfaction algorithm enforcing TwistAmp Assay Design Manual rules (≥30 nt upstream, ≥15 nt downstream, dT-fluorophore/quencher coupling).
• Configurable Reaction Temperatures: RAA probe Tm floor is now dynamically configurable (qc.probe_tm_min) for isothermal assays (37–42°C).

📚 Scientific References & Citations

• Integrated peer-reviewed thermodynamic literature (SantaLucia 1998/2004, Owczarzy 2004/2008, Untergasser 2012, Piepenburg 2006).
• Added standardized CITATION.cff for academic repository citations.
• Added comprehensive in-silico benchmarking suite (scripts/benchmark_validation.py).

🧪 Automated Test Suite

• 1,425 tests passing (100%).

v1.0.1 - Hotfix: Package structure

🐛 Hotfix Release

Fixed

• Added missing init.py files to core, config, and workflows packages
• Package now correctly includes all 132 source files

Upgrade

pip install --upgrade primerlab-genomic

v1.0.0 - Stable Release 🎉

🎉 PrimerLab v1.0.0 - Stable Release

First production-ready release of PrimerLab!

Highlights

• ✅ 1286+ passing tests with comprehensive coverage
• ✅ Full PCR Workflows: Standard PCR, qPCR, Nested PCR, Semi-Nested PCR
• ✅ Complete Analysis Suite: BLAST off-target, In-silico PCR, Dimer matrix
• ✅ Multiple Installation Options: Docker, Conda, Pip
• ✅ Comprehensive Documentation: API reference, CLI guide, tutorials

Installation

PyPI (Recommended)

pip install primerlab-genomic

Docker

docker pull ghcr.io/engkinandatama/primerlab-genomic:1.0.0
docker run ghcr.io/engkinandatama/primerlab-genomic:1.0.0 --version

Conda

git clone https://github.com/engkinandatama/primerlab-genomic.git
cd primerlab-genomic
conda env create -f environment.yml
conda activate primerlab
pip install -e .

Quick Start

# PCR primer design
primerlab run pcr --config your_config.yaml

# qPCR with TaqMan probe
primerlab run qpcr --config qpcr_config.yaml

# Nested PCR
primerlab run nested --config nested_config.yaml

What's New in v1.0.0

Added

• Production Status: Changed from Beta to Production/Stable
• Report Standardization: Unified report format across all workflows
• Documentation: Complete tutorials, API reference, configuration guide
• Docker Support: Multi-stage build with ViennaRNA and BLAST+ included
• PyPI Publishing: Automated release via GitHub Actions

Changed

• Version bump from 0.9.x to 1.0.0
• Updated all badges and documentation to reflect stable release

Documentation

• 📚 Full Documentation
• 🚀 Getting Started
• 📖 CLI Reference
• 🔧 API Reference
• 📝 Tutorials

Requirements

• Python 3.10+
• primer3-py >= 2.0.0
• biopython >= 1.80
• Optional: ViennaRNA, BLAST+ (included in Docker)

Full Changelog

See CHANGELOG.md

v0.1.0 Technical Preview

Changelog

All notable changes to this project will be documented in this file.

The format is based on Keep a Changelog,
and this project adheres to Semantic Versioning.

[0.1.0] - 2025-11-27

Added

• Core Framework:
  • Modular 3-layer architecture (CLI, Workflows, Core).
  • Unified YAML configuration system.
  • Robust logging and progress tracking.
• PCR Workflow:
  • Automated primer design using Primer3.
  • Comprehensive QC (Tm, GC, Hairpin, Homodimer, Heterodimer).
  • JSON and Markdown report generation.
• qPCR Workflow:
  • TaqMan® probe design support.
  • Primer-Probe compatibility checks.
  • Efficiency estimation logic.
• API:
  • Programmatic access via primerlab.api.public.
  • Functions: design_pcr_primers, design_qpcr_assays.
• Testing:
  • Full pytest suite covering PCR, qPCR, and API.
  • CI/CD integration via GitHub Actions.

Fixed

• Critical bug in reverse primer coordinate calculation (Primer3 3' index vs 5' start).
• QC silent pass bug when ViennaRNA is missing (now raises explicit warnings).
• Timeout handling for stuck Primer3 processes.

Changed

• Switched to pyproject.toml for modern packaging (PEP 621).
• Updated documentation structure for long-term roadmap.