PROJECT HELIX-HTT | Huntington’s-Adjacent Neuro-Oncology Vaccine Program
DOCUMENT CONTROL HEADER
Program: PROJECT HELIX-HTT
Sub-Program: SCF Therapeutic Vaccine Design Platform
Module: SCF-ARGEN-HTT-NO-01 Antigen-Ranking Engine
Document Code: SCF-PLAT-VENDOR-0001
Purpose: Technology Platform Selection & Assay Infrastructure Specification
EXECUTIVE SUMMARY
The SCF Antigen-Ranking Engine requires four core discovery technologies:
- Whole Exome Sequencing (WES) / Whole Genome Sequencing (WGS)
- RNA Sequencing (RNA-seq)
- HLA Typing
- Immunopeptidomics
These technologies form the foundational data layers for:
- Neoantigen discovery
- Tumor specificity scoring
- Antigen presentation prediction
- Vaccine candidate prioritization
The recommended architecture emphasizes:
- Clinical-grade reproducibility
- Regulatory acceptability
- Scalability
- Multi-omics integration
- Future IND compatibility
PLATFORM 1
WHOLE EXOME / WHOLE GENOME SEQUENCING
Purpose
Identify:
- Somatic mutations
- Indels
- Structural variants
- Gene fusions
- Neoantigen-generating mutations
Preferred Discovery Platform
Illumina
Recommended Systems:
Platform | Use Case |
NovaSeq X Plus | Large-scale discovery |
NovaSeq 6000 | Standard translational program |
NextSeq 2000 | Pilot studies |
Advantages:
- Industry standard
- FDA familiarity
- Broad vendor ecosystem
- Excellent accuracy
Alternative Long-Read Platform
PacBio Official Website
Recommended:
- Revio System
Advantages:
- Repeat expansions
- Structural variants
- Complex genomic architecture
Particularly valuable for:
- HTT repeat biology
- Repeat instability research
Bioinformatics Pipeline
Recommended:
- BWA-MEM2
- GATK
- Mutect2
- Strelka2
- Manta
Output:
- VCF
- Mutation burden
- Clonality
PLATFORM 2
RNA SEQUENCING
Purpose
Confirm:
- Gene expression
- Tumor-specific transcription
- Neoantigen expression
- Immune microenvironment
Preferred Platform
Illumina
Systems:
- NovaSeq
- NextSeq
Preferred Depth:
Application | Reads |
Standard RNA-seq | 50M |
Deep RNA-seq | 100M+ |
Fusion discovery | 150M+ |
Single Cell Extension
10x Genomics
Recommended:
- Chromium X
Allows:
- Tumor cell profiling
- Immune cell profiling
- Microglial profiling
Spatial Transcriptomics
10x Genomics Visium
Purpose:
- Antigen geography
- Immune infiltration mapping
- Vaccine accessibility analysis
PLATFORM 3
HLA TYPING
Purpose
Determine:
- Antigen presentation capacity
- MHC Class I
- MHC Class II
Required for:
- Neoantigen prediction
- Vaccine design
Preferred Platform
Illumina
Methods:
- TruSight HLA
Advantages:
- High-resolution typing
- Clinical adoption
- Regulatory familiarity
Alternative Platform
Omixon HLA Solutions
Advantages:
- Ultra-high-resolution HLA typing
- Neoantigen programs
- Transplant-grade accuracy
HLA Analysis Software
Recommended:
- OptiType
- HLA-HD
- arcasHLA
Outputs:
- HLA-A
- HLA-B
- HLA-C
- DR
- DQ
PLATFORM 4
IMMUNOPEPTIDOMICS
Purpose
Confirm actual peptide presentation.
This is arguably the most important validation layer.
Prediction ≠ Presentation.
Immunopeptidomics verifies:
Is the peptide truly displayed on the tumor cell surface?
Preferred Mass Spectrometry Platforms
Thermo Fisher Scientific
Recommended:
- Orbitrap Astral
- Orbitrap Eclipse
- Orbitrap Exploris
Advantages:
- Industry-leading sensitivity
- Neoantigen discovery
- MHC peptide detection
Alternative Platform
Bruker Corporation
Recommended:
- timsTOF Ultra
- timsTOF SCP
Advantages:
- Single-cell compatible workflows
- Excellent peptide sensitivity
Preferred Immunopeptidomics Service Providers
Cedars-Sinai Applied Genomics, Computation & Translational Core
Broad Institute
Moffitt Cancer Center Proteomics Core
PLATFORM 5
SCF MICROENVIRONMENT LAYER
RHENOVA Biomarker Platform
Purpose:
Measure:
- Hypoxia
- Oxidative stress
- Immune suppression
- Neuroimmune compatibility
Recommended Assays
Hypoxia
Marker
HIF-1α
CAIX
VEGF
pO₂
Oxidative Stress
Marker
8-OHdG
MDA
GSH:GSSG
ROS load
Immune Terrain
Marker
CD8
IFN-γ
CXCL9
CXCL10
PD-L1
Microglial State
Marker
IBA1
TREM2
IL-1β
TNF-α
SCF DATA INTEGRATION STACK
Cloud Infrastructure
Amazon Web Services (AWS) Health & Life Sciences
or
Google Cloud Life Sciences
Analysis Layer
Recommended:
- Python
- R
- Nextflow
- Snakemake
Vaccine Ranking Engine
Inputs:
- Genomics
- Transcriptomics
- HLA
- Immunopeptidomics
- RHENOVA
Outputs:
- Antigen Priority Score (APS)
- SCF Microenvironment Score (MES)
- CNS Safety Score
- Final Vaccine Rank
RECOMMENDED MINIMUM VIABLE DISCOVERY STACK
For PROJECT HELIX-HTT Phase I:
Genomics
- Illumina NovaSeq 6000
RNA-seq
- Illumina NovaSeq 6000
HLA
- Omixon HLA Solutions
Immunopeptidomics
- Thermo Fisher Scientific Orbitrap Astral
Single Cell
- 10x Genomics Chromium X
Cloud
- AWS Health & Life Sciences
STRATEGIC NEXT STEPS
Research Pathways
- Build SCF Antigen-Ranking Database Schema
- Develop SCF Vaccine Candidate Knowledge Graph
- Build AI Neoantigen Prioritization Engine
Development Pathways
- Generate SCF-ARGEN Data Dictionary
- Create SCF Antigen Priority Score Calculator
- Build IND-Facing Vaccine Discovery Workflow Package
This platform stack provides a realistic, modern discovery infrastructure that is consistent with current cancer vaccine, genomics, and immunopeptidomics programs while supporting the SCF multi-omics and microenvironment-ranking framework.