The Iyengar Flavor Index: A Receptor-Normalized Cross-Modal Flavor Measurement Standard Spanning Seven Chemosensory Receptor Classes

Version 1.0 — November 2026. Initial preprint deposit. The Iyengar Flavor Index: A Receptor-Normalized Cross-Modal Flavor Measurement Standard Spanning Seven Chemosensory Receptor Classes Priyanca Iyengar Ford, Scoville Splice LLC · ORCID 0000-0003-0395-1752Preprint · Scoville Splice Research Series · Paper 4 of 11 (Anchor Methodology) · 2026-11-01 ─────────────────────────────────────────────────────────────OVERVIEW This paper introduces the Iyengar Flavor Index (IFI), a unified receptor-normalized measurement standard for quantifying flavor potency across seven chemosensory receptor classes. IFI provides a single comparable number for heat, sweetness, umami, bitterness, kokumi, cooling, and pungent warmth — enabling cross-modal comparison of flavor compounds and engineered food ingredients for the first time. This paper serves as the anchor methodology document for the Scoville Splice Research Series (Papers 3–10). All IFI values reported across the series are defined and calibrated here. ─────────────────────────────────────────────────────────────MOTIVATION AND NAMING PRECEDENT The food-science literature has accumulated isolated receptor-specific potency scales over more than a century: Scoville (1912, J Am Pharm Assoc 1:453) introduced organoleptic heat measurement; Sørensen (1909, C R Trav Lab Carlsberg 8:1) introduced the pH scale for hydrogen ion activity; Jenkins and Wolever (1981, Am J Clin Nutr 34:362, University of Toronto) introduced the Glycemic Index for carbohydrate metabolism. Each of these scales has become a durable standard by virtue of: (1) a single reference compound normalized to 1,000 index units, (2) a simple ratio formula, and (3) backward compatibility with prior measurement conventions. IFI follows the same principles. It is named the Iyengar Flavor Index after Priyanca Iyengar, who developed the framework and defined all seven sub-scales. The IFI abbreviation should be retained in all citations; the long form "Iyengar Flavor Index" should appear on first use in any document that cites this methodology. ─────────────────────────────────────────────────────────────THE IFI FORMULA IFI(compound, modality) = 1,000 × EC₅₀(reference compound) / EC₅₀(compound) Where: · EC₅₀ values are measured in the same units (typically nM or µM) · Higher IFI = greater receptor potency · IFI 1,000 = exactly reference compound potency · IFI 2,000 = twice reference compound potency · Dimensionless ratio; scale is defined separately per sub-scale by the reference compound ─────────────────────────────────────────────────────────────THE SEVEN IFI SUB-SCALES IFI-H (Heat): Receptor TRPV1 (Transient Receptor Potential Vanilloid 1, human NM_080706). Reference compound: capsaicin, EC₅₀ = 0.5 µM (Caterina et al. 1997, Nature 389:816). Assay: HPLC (ASTA Method 21.3) for established capsaicinoids; Ca²⁺-flux (HEK293 + TRPV1 + Gα16, Fluo-4/AM) for novel compounds. IFI-H is exactly equal to the Scoville Heat Unit (SHU) scale (backward compatible with Scoville 1912). IFI-S (Sweetness): Receptor TAS1R2/TAS1R3 heterodimer. Reference compound: sucrose, EC₅₀ = 20 mM (Xu et al. 2004, Cell 119:851). Assay: Ca²⁺-flux (HEK293 + TAS1R2 + TAS1R3 + Gα16, Fluo-4/AM). IFI-S 1,000 = sucrose sweetness; IFI-S 2,200,000 (brazzein in Sweet Heat D.N.R.) indicates 2,200× sucrose equivalent sweetness. IFI-U (Umami/Savory): Receptor mGluR1 (metabotropic glutamate receptor 1). Reference compound: L-glutamate, EC₅₀ = 1 mM (Chaudhari et al. 2000, Nat Neurosci 3:113). Assay: Ca²⁺-flux (HEK293 + GRM1 + Gα16). Target for umami-engineered cultivars (Paper 5): IFI-U ≥ 800. IFI-B (Bitterness): Receptor TAS2R38. Reference compound: quinine, EC₅₀ = 1 µM (Behrens et al. 2004, J Biol Chem 279:14381). Assay: Ca²⁺-flux (HEK293 + TAS2R38 + Gα16). IFI-B target for engineered D.N.R.: < 40 (via Zero-Bitter strategy, Paper 6). Capsicum naturally runs ~150 IFI-B; Brassica ~770 IFI-B. IFI-K (Kokumi): Receptor CaSR (Calcium-Sensing Receptor). Reference compound: γ-glutamyl-valyl-glycine (γ-Glu-Val-Gly), EC₅₀ = 0.1 mM (Ohsu et al. 2010, Nat Chem Biol 6:843). Assay: Ca²⁺-flux (HEK293 + CASR + Gα16). Target for kokumi-engineered cultivars (Paper 7): IFI-K ≥ 2,400. IFI-C (Cooling): Receptor TRPM8 (Transient Receptor Potential Melastatin 8). Reference compound: menthol, EC₅₀ = 0.1 µM (McKemy et al. 2002, Nature 416:52). Assay: Ca²⁺-flux (HEK293 + TRPM8 + Gα16). Target for cooling-engineered cultivars (Paper 9): IFI-C ≈ 85,000. IFI-P (Pungent Warmth): Receptor TRPA1 (Transient Receptor Potential Ankyrin 1). Reference compound: allyl-isothiocyanate (AITC), EC₅₀ = 10 µM (Jordt et al. 2004, Nature 427:260). Assay: Ca²⁺-flux (HEK293 + TRPA1 + Gα16). Target for TRPA1-spectrum cultivars (Paper 10): IFI-P ≈ 170,000 (cinnamaldehyde-expressing Capsicum). ─────────────────────────────────────────────────────────────IFI MEASUREMENT ASSAYS For IFI-H: HPLC per ASTA Method 21.3. Provides direct capsaicinoid quantification; historical SHU values convert directly to IFI-H with no adjustment. For IFI-S, IFI-U, IFI-B, IFI-K, IFI-C, IFI-P: Ca²⁺-flux assay. HEK293 cells stably transfected with target receptor gene + Gα16 (promiscuous G-protein enabling Ca²⁺ readout for all GPCRs). Dye: Fluo-4/AM. Readout: ΔF/F₀. EC₅₀ determination: 10-point dose-response curve (0.001× to 1,000× reference EC₅₀), Hill fit. IFI calculated from measured EC₅₀ vs. reference compound EC₅₀ run in same assay plate. ─────────────────────────────────────────────────────────────D.N.R. FULL SPECTRUM IFI PROFILE D.N.R. (SS-CV-010, Capsicum annuum, 2,956,310 SHU) represents the most complex IFI target in the series. D.N.R. v1 (Papers 1–2, SS Triple only): IFI-H: 2,956,310 | IFI-S: ~200 | IFI-U: ~280 | IFI-B: ~150 | IFI-K: ~80 | IFI-C: 0 | IFI-P: 0 D.N.R. Full Spectrum (all 7 dimensions, Papers 3–10): IFI-H: 2,956,310 | IFI-S: ~2,200,000 | IFI-U: ~900 | IFI-B: ~30 | IFI-K: ~2,400 | IFI-C: ~85,000 | IFI-P: ~170,000 The Full Spectrum profile is achieved through the sequential engineering modules described in Papers 3, 5, 6, 7, 9, and 10 of this series. Each module is metabolically orthogonal to the capsaicin pathway (validated by FBA, each sub-paper). ─────────────────────────────────────────────────────────────LIMITATIONS IFI values for novel compounds in this series are computational projections based on in vitro receptor EC₅₀ data from the literature and FBA-modeled in-fruit compound concentrations. No human sensory panel data are reported in this preprint series. Receptor assay conditions (cell line, expression vector, passage number, assay temperature) affect absolute EC₅₀ values; IFI values should be treated as order-of-magnitude estimates until confirmed by standardized laboratory measurement. The IFI-S sub-scale does not account for sweet protein stability in acidic food matrices; Paper 3 addresses this limitation for brazzein specifically. ─────────────────────────────────────────────────────────────INTELLECTUAL PROPERTY This methodology is incorporated by reference in U.S. Provisional Patent Application 64/188,197 (filed October 30, 2026, Confirmation No. 4455) and 64/172,827 (filed October 9, 2026). Assignee: Scoville Splice LLC. Non-provisional due: October 9, 2027. ─────────────────────────────────────────────────────────────RELATED WORKS IN THIS SERIES · Paper 1 (Capsicum cultivar design, DOI: 10.5281/zenodo.23743695) — establishes IFI-H = 2,956,310 for D.N.R.· Paper 2 (Cross-species engineering, DOI: 10.5281/zenodo.23749878) — reports IFI-H values for 57 cross-species products· Papers 3, 5, 6, 7, 9, 10 (flavor modality engineering) — all IFI values in those papers are defined here ─────────────────────────────────────────────────────────────KEYWORDS flavor index, chemosensory receptors, TRPV1, TAS1R2/TAS1R3, mGluR1, TAS2R38, CaSR, TRPM8, TRPA1, receptor normalization, Iyengar Flavor Index, IFI, cross-modal flavor measurement, precision flavor engineering, flavor standardization, Ca2+ flux assay, HEK293, HPLC, capsaicin, sucrose, glutamate, quinine, kokumi, menthol, allyl-isothiocyanate, D.N.R., SS-CV-010