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Description

Hierarchical Adaptive 'RT-QuIC' Classification for Complex Matrices.

Extends 'RT-QuIC' (Real-Time Quaking-Induced Conversion) statistical analysis to complex environmental matrices through hierarchical adaptive classification. 'KWELA' is named after a deity of the Fore people of Papua New Guinea, among whom Kuru, a notable human prion disease, was identified. Implements a 6-layer architecture: hard gate biological constraints, per-well adaptive scoring, separation-aware combination, Youden-optimized cutoffs, replicate consensus, and matrix instability detection. Features dual-mode operation (diagnostic/research), auto-profile selection (Standard/Sensitive/Matrix-Robust), RAF integration for artifact detection, matrix-aware baseline correction, and multiple consensus rules. Methods include energy distance (Szekely and Rizzo (2013) <doi:10.1016/j.jspi.2013.03.018>), CRPS (Gneiting and Raftery (2007) <doi:10.1198/016214506000001437>), SSMD (Zhang (2007) <doi:10.1016/j.ygeno.2007.01.005>), and Jensen-Shannon divergence (Lin (1991) <doi:10.1109/18.61115>). This package implements methodology currently under peer review; please contact the author before publication using this approach. Development followed an iterative human-machine collaboration where all algorithmic design, statistical methodologies, and biological validation logic were conceptualized, tested, and iteratively refined by Richard A. Feiss through repeated cycles of running experimental data, evaluating analytical outputs, and selecting among candidate algorithms and approaches. AI systems ('Anthropic Claude' and 'OpenAI GPT') served as coding assistants and analytical sounding boards under continuous human direction. The selection of statistical methods, evaluation of biological plausibility, and all final methodology decisions were made by the human author. AI systems did not independently originate algorithms, statistical approaches, or scientific methodologies.

KWELA

CRAN status R-CMD-check

KWELA extends RT-QuIC (Real-Time Quaking-Induced Conversion) statistical analysis to complex environmental matrices through hierarchical adaptive classification.

KWELA is named after a deity of the Fore people of Papua New Guinea, among whom Kuru, a notable human prion disease, was identified.

Installation

# Install from CRAN
install.packages("KWELA")

# Or install development version from GitHub
# install.packages("devtools")
devtools::install_github("RFeissIV/KWELA")

6-Layer Architecture

KWELA implements a hierarchical adaptive classification system with dual-mode operation:

LayerFunctionDescription
1Hard GateBiological constraint filter with stochastic rescue (research mode)
2Per-Well ScoringProfile-dependent adaptive transforms
3Adaptive CombinationSeparation-aware score combiner
4Adaptive CutoffYouden-optimized threshold per plate
5Replicate ConsensusTreatment-level classification
6Instability DetectionMatrix interference override

Quick Start

library(KWELA)

# Diagnostic mode (default) — deterministic, no stochastic rescue
result <- kwela_analyze(your_data)

# Research mode — full adaptive architecture
result <- kwela_analyze(your_data, mode = "research")

# Get treatment-level summary
summary <- kwela_summarize(result)

# View diagnostics (includes instability flags)
diag <- kwela_diagnostics(result)

Dual-Mode Operation

FeatureDiagnostic (default)Research
Stochastic rescueDisabledEnabled
Stochastic score in combinerExcludedIncluded
TTT/MP/RAF scoringFullFull
Instability detectionEnabledEnabled

Profiles

ProfileWhen to UseCohen's d
standardClean assay, strong separation> 3.0
sensitiveSpiked samples, moderate separation1.5 - 3.0
matrix_robustEnvironmental matrices, poor separation< 1.5
autoLet KWELA decide based on data-

Consensus Rules

RuleClassification Criteria
strictAll wells must be positive
majority>50% of wells positive (default)
flexibleAny well positive
thresholdMean score >= threshold

Key Features

  • Dual-mode operation: diagnostic (deterministic) vs research (adaptive)
  • Instability detection: 6 deterministic metrics for matrix interference
  • Auto-profile selection based on PC/NC separation quality
  • RAF integration for artifact detection and quality scoring
  • Group-aware mixed-assay support (RT-QuIC + Nano-QuIC)
  • Matrix-aware baseline correction with per-group local controls
  • Comprehensive metrics: CRPS, Wasserstein, Energy distance, SSMD, JSD

Citation

If you use KWELA in your research, please cite:

Feiss RA IV (2026). KWELA: Hierarchical Adaptive RT-QuIC Classification.
R package version 1.0.0. https://CRAN.R-project.org/package=KWELA

Note

This package implements methodology currently under peer review. Please contact the author before publication using this approach.

Development & AI Disclosure

Development followed an iterative human-machine collaboration where all algorithmic design, statistical methodologies, and biological validation logic were conceptualized, tested, and iteratively refined by Richard A. Feiss through repeated cycles of running experimental data, evaluating analytical outputs, and selecting among candidate algorithms and approaches. AI systems (Anthropic Claude and OpenAI GPT) served as coding assistants and analytical sounding boards under continuous human direction. The selection of statistical methods, evaluation of biological plausibility, and all final methodology decisions were made by the human author. AI systems did not independently originate algorithms, statistical approaches, or scientific methodologies.

License

MIT © Richard A. Feiss IV.

Metadata

Version

1.0.0

License

Unknown

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