Method for determining the scent note of a fragrance composition, method for determining a fragrance composition and corresponding system

Abstract

A method (100) for determining the fragrance notes of a composition, comprising: a step (105) of inputting at least one volatile molecule digital identifier on a computer interface, wherein the volatile molecule digital identifier represents an aromatic volatile molecule, and the input defines a formula; a step (110) of calculating, by the computing system, a value representing the influence of each molecule on the activity level of an olfactory receptor, represented by an olfactory receptor digital identifier, for at least one volatile molecule digital identifier of the formula, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, and the association is a many-to-many association; and a step (115) of determining, by the computing system, a value representing at least one olfactory note forming the composition as a function of the calculated influence of the at least one olfactory receptor activity level and a value representing an olfactory receptor activation threshold for the formula, wherein each olfactory receptor digital identifier is associated with one olfactory note digital identifier, and the association is a one-to-one association.

Description

[Technical field]

[0001] The present invention relates to a method for determining the tonality of a fragrance composition, a method for determining a fragrance composition, a system for determining the tonality of a fragrance composition and a system for determining a fragrance composition. It is particularly applicable to the fields of fragrance design and olfactometry, perfumery, fine fragrance perfumery and flavor design. The present invention also applies to odorless or non-perfumed compositions intended to enhance or reduce the perceptible specific tonality of other compositions.

[0002] 2. Background of the Invention Since the first identification of odorant receptors in 1991, much has been done to improve our understanding of smell and how humans perceive volatile chemicals. At the periphery of the human olfactory system, the main olfactory epithelium lining the nasal cavity contains millions of olfactory sensory neurons (OSNs), each expressing a single member from a family of approximately 400 intact odorant (olfactory) receptor (OR) genes. Each OR can be activated by several volatile compounds, but conversely, a single volatile compound may activate several ORs. This results in a combinatorial OSN activation code for each volatile chemical and its mixtures. Each receptor is stochastically expressed in a monogenic and monoallelic manner in OSNs, resulting in one OSN type for each OR allele present in the genome. Depending on the frequency of genetic selection for each OR, distinct subsets of the OSN population are specialized for each OSN type. Each of these subpopulations of OSN types provides a distinct channel of information about the molecular identity, or identity, and concentration of the volatile compound in contact at any given time. The level of activity induced in each OSN of each OSN type differs according to the concentration of the volatile compound to which that OR is receptive, and according to the binding and activation parameters associated with each OR-compound pair. Furthermore, some OR-ligand pairs induce or enhance OSN activity, whereas others reduce or prevent OSN activity. This can occur competitively, when a compound binds to an OR, or noncompetitively, when multiple compounds can bind to an OR simultaneously. The resulting combinatorial logic of these approximately 400 input channels (i.e., the peripheral olfactory system) is transformed by subsequent downstream neural networks to provide us with the sense of smell.

[0003] The Fragrance & Flavor (F&F) industry is constantly searching for new ingredients, novel fragrance and flavor applications, improved sensory experiences, and more stable, biodegradable and non-toxic compounds.

[0004] Because an odorant or aroma molecule may interact with several olfactory receptors (ORs), it is often difficult to infer the odor notes of a volatile compound based solely on its chemical structure. Conversely, because each OR may interact with several odorants or aroma molecules with different chemical structures and elicit a different set of odor notes, it is often difficult to infer the nature of the information encoded by an OR.

[0005] There remains a need to predict at least one olfactory note of a given compound or composition based on OR activation and to facilitate the discovery of new fragrance and flavor ingredients relevant to the F&F industry.

[0006] Summary of the Invention The present invention is intended to remedy all or part of these drawbacks.

[0007] To this effect, according to a first aspect, the present invention is directed to a method for determining the olfactory notes of a composition, said method comprising the following steps: - inputting at least one volatile molecule digital identifier on a computer interface, said volatile molecule digital identifier representing an aromatic volatile molecule, said input defining a formula; - calculating, by a computing system, for at least one volatile molecule digital identifier of the formula, a value representing the effect of each said molecule on an olfactory receptor activity level, as represented by an olfactory receptor digital identifier, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, the association being a many-to-many association; - determining, by the computing system, for the formula, a value representative of at least one fragrance note forming the composition as a function of the calculated influence of at least one olfactory receptor activity level and a value representative of an olfactory receptor activation threshold, wherein each olfactory receptor digital identifier is associated with one fragrance note digital identifier, said association being a one-to-one association; Includes.

[0008] Such prescriptions allow for automatic prediction of the olfactory notes of dynamically input compositions, enabling more efficient and productive fragrance and flavor design cycles.

[0009] In certain embodiments, the subject matter of the method of the present invention includes, downstream of the calculating step, a step of calculating, by a computing system, a total activity level for at least one olfactory receptor as a function of at least one effect on the calculated activity level.

[0010] Such a definition makes it possible to predict the overall impact on the perceptibility of the odor note of a given composition, as opposed to a molecule-by-molecule approach.

[0011] In a particular embodiment, the subject of the method of the present invention is the method comprising the following steps: - modifying, on a computer interface, a value representative of the fragrance tonality of the composition; - calculating, by a computing system, a change in the total activity level of at least one odorant receptor; - determining, by a computing system, a set of at least one volatile molecular digital identifier exhibiting a total activity level impact value equal to the calculated total activity level change; - providing said set to a computer interface; Includes.

[0012] Such a provision makes it possible to automatically modify the formula by inserting new molecules into it or by removing input molecules from it, so as to reach a target composition of at least one odor note.

[0013] In a particular embodiment, each scent note is associated with a scent note digital identifier, and the method comprises the step of automatically selecting a scent note as a function of a comparison of the scent note digital identifier of the composition with a set of at least one predefined scent note digital identifier, and the step of modifying the value representative of the scent of said selected scent note identifier of the composition is configured to modify the value of said selected scent note identifier to a reduced value, preferably zero.

[0014] Such provisions make it possible to automatically remove scent notes that are deemed unpleasant or unwanted.

[0015] In certain embodiments, the value representing the effect of a molecule on an olfactory receptor activity level, as represented by the volatile molecular digital identifier, is: - activation of said odorant receptors, - inactivation of said odorant receptors, - Enhancement of the above odorant receptors and / or - Inhibition of the above odorant receptors Represents.

[0016] Such embodiments make it possible to precisely define the type of effect that volatile molecules can have on odorant receptors.

[0017] In certain embodiments, the determining step is configured to provide at least one volatile molecule digital identifier that presents a value representative of an effect on the activity of an olfactory receptor associated with the altered olfactory note during the altering step, said effect corresponding to either an enhancement of said olfactory receptor or an inhibition of said olfactory receptor.

[0018] Such odor tone modifiers are relevant in the context of perfumery applications. For example, adding volatile molecules that reduce the activity of malodor receptors to a formula will result in a reduction in the perception of ambient malodors (applied in toilets, cat litter, deodorants, laundry, etc.). Similarly, enhancing the activity of receptors with enhancers (e.g. top notes) with faster release kinetics may allow selectively enhancing the base note odor tone at an earlier stage of the fragrance experience than would normally occur. In a particular embodiment, the subject of the method of the present invention is the following steps: - selecting, on a computer interface, a volatile molecular digital identifier of the formula; - determining, by the computing system, at least a set of at least one volatile molecule digital identifier that exhibits a value representing an effect on the activity level of the olfactory receptor equal to a value representing an effect of the selected volatile molecule digital identifier on the activity level of the olfactory receptor; - providing said set to a computer interface; Includes.

[0019] Such a provision allows for the automatic determination of replacement molecules that can be used to reformulate the formula, which may have better environmental or cost impacts than the originally entered molecule.

[0020] In a particular embodiment, the subject of the method of the present invention is the method comprising the following steps: - selecting at least two volatile molecule digital identifiers of the formula, wherein at least two of said volatile molecules are associated with the activation of at least two different olfactory receptors, called "target receptors"; - determining one volatile molecule digital identifier that exhibits a value representative of the effect on the activity level of each target receptor equal to a value representative of the effect of the selected volatile molecule digital identifier on the activity level of the odorant receptor; - providing the determined volatile molecular digital identifier to a computer interface; Includes.

[0021] Such a provision allows for the replacement of several molecules with a single molecule, making it possible to optimize the formula being designed.

[0022] In certain embodiments, the subject method of the present invention includes, downstream of any of the determining steps, a step of estimating an amount for at least one of said volatile molecular digital identifiers, said amount being used in a downstream step of providing a set of at least one volatile molecular digital identifier.

[0023] Such a definition makes it possible to predict both the molecules that will be added / removed from a formula and the amounts of such molecules that will be added / removed.

[0024] In certain embodiments, the step of determining, by the computing system, at least a set of at least one volatile molecular digital identifier is based on the following rules: - a first rule, wherein the determined set of at least one volatile molecular digital identifier is configured to present a minimum number of volatile molecular digital identifiers; - a second rule, in which the determined set of at least one volatile molecular digital identifier is configured to present a minimum total quantity indicator of the corresponding volatile molecular digital identifier; - a third rule, wherein the determined set of at least one volatile molecular digital identifier is configured to present a minimum number of adversely affecting volatile molecular digital identifiers; - a fourth rule, according to which at least one volatile molecule digital identifier is associated with a volatile molecule deliverability indicator, said rule being configured to match the determined set of at least one volatile molecule digital identifier as a function of said volatile molecule deliverability indicator for the volatile molecule digital identifiers in the set; - a fifth rule, wherein the set of at least two volatile molecular digital identifiers is configured to minimize the overlap of odorant receptors activated by said set of molecules; - a sixth rule, wherein the set of at least two volatile molecular digital identifiers is configured to minimize modulation of odorant receptors activated by the set of molecules; - a seventh rule, wherein the determined set of at least one volatile molecular digital identifier is configured to maximize the negative modulation or inhibition of odorant receptors associated with a given undesirable olfactory note; - an eighth rule, wherein the determined set of at least one volatile molecular digital identifier is configured to maximize a positive modulation or enhancement of an odorant receptor associated with a predetermined desired olfactory note; and / or - a ninth rule, wherein the determined set of at least one volatile molecule digital identifier is configured to minimize or maximize at least one cost function, and each volatile molecule is associated with at least one value representing a cost. Execute an optimization rule that is at least one of:

[0025] Such an embodiment allows optimizing the formula according to predefined optimization rules.

[0026] In certain embodiments, the subject method of the present invention includes a step of inputting an amount of at least one input volatile molecule on a computer interface, said amount being used by the computing system in a step of calculating a value representing the effect on the activity level of an olfactory receptor for at least one volatile molecule digital identifier of the formula.

[0027] Such an embodiment makes it possible to take into account the amount as a parameter for the odor note prediction.

[0028] In certain embodiments, at least one volatile molecule digital identifier is associated with a volatile molecule delivery capability index, and at least one of the calculating or determining steps is performed as a function of the volatile molecule delivery capability index associated with the at least one input volatile molecule digital identifier.

[0029] Such an embodiment makes it possible to more accurately determine the odour notes in a composition derived from an input formula, or conversely, to accurately determine the volatile molecules in a formula as a function of the input odour notes.

[0030] In certain embodiments, the volatile molecule delivery capability index is representative of the substrate on which the associated volatile molecule is disposed.

[0031] In a second aspect, the present invention is directed to a method for formula determination, the method comprising the steps of: - inputting, on a computer interface, for at least one fragrance note digital identifier, a value representative of the fragrance note of the composition derived from the formula to be determined; - determining, by a computing system, for the formula to be determined, a value of an olfactory receptor activity level for at least one olfactory receptor digital identifier representing an olfactory receptor as a function of at least one value representing at least one olfactory note of said composition, wherein each olfactory receptor digital identifier is associated with one olfactory note digital identifier, said association being a one-to-one association; - determining a formula represented by at least a set of at least one volatile molecule digital identifier that exhibits a value representing an effect on the activity level of the olfactory receptor digital identifier equal to a determined value representing the activity level on the olfactory receptor, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, the association being a many-to-many association; Includes.

[0032] The relationship between the volatile molecule digital identifiers and the odorant receptor digital identifiers may be one-to-many or many-to-one in certain embodiments.

[0033] Such a definition allows the reverse design of formulas, where the user determines the odour note to be reached and then a formula is deduced as a result of said target odour note.

[0034] In a third aspect, the present invention is directed to a system for determining a composition's odor note, the system comprising: - means for inputting at least one volatile molecule digital identifier, said volatile molecule digital identifier representing a fragrance volatile molecule, said input defining a formula; and - means for calculating, for at least one volatile molecule digital identifier of the formula, a value representing the effect of each said molecule on an olfactory receptor activity level, as represented by an olfactory receptor digital identifier, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, said association being a many-to-many association; - means for determining, for a composition, a value representative of at least one olfactory note forming the composition as a function of the effect of at least one calculated olfactory receptor activity level and a value representative of an olfactory receptor activation threshold, wherein each olfactory receptor digital identifier is associated with at least one olfactory note digital identifier, said association being a one-to-one association; Equipped with.

[0035] Such a system offers the same advantages as the corresponding methods.

[0036] In a fourth aspect, the present invention is directed to a formula determination system, said system comprising the following means: - means for inputting, on a computer interface, for at least one fragrance note digital identifier, a value representative of the fragrance note of the composition resulting from the formula to be determined; - means for determining, by a computing system, for a formula to be determined, a value of an olfactory receptor activity level for at least one olfactory receptor digital identifier representing an olfactory receptor as a function of at least one value representing at least one olfactory note of said composition, wherein each olfactory receptor digital identifier is associated with one olfactory note digital identifier, said association being a one-to-one association; - a means for determining a formula represented by at least a set of at least one volatile molecule digital identifier that exhibits a value representing an effect on the activity level of the olfactory receptor digital identifier equal to a determined value representing the activity level on the olfactory receptor, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, the association being a many-to-many association; and Equipped with.

[0037] Such a system offers the same advantages as the corresponding methods. [Brief description of the drawings]

[0038] Other advantages, objects and specific features of the present invention will become apparent from the following non-exhaustive description of at least one specific method or system that is the subject of this invention, taken in conjunction with the drawings attached hereto. [Figure 1] FIG. 1 shows a schematic representation of a first particular sequence of steps of the subject method of the invention. [Diagram 2] FIG. 2 shows a schematic representation of a second particular sequence of steps of the subject method of the invention. [Diagram 3] FIG. 1 shows a schematic diagram of a first particular embodiment of the subject system of the invention. [Figure 4] FIG. 2 shows a schematic diagram of a second particular embodiment of the subject system of the invention. [Diagram 5] FIG. 1 shows an example of the contents of four fragrance accords (A, B, C, and D) that activate ORD1, OR8B3, and OR5AU1, and their respective composition ratios. [Figure 6] FIG. 1 shows the activity levels of components that activate OR8D1, OR8B3, and OR5AU1 in percentage. [Figure 7] FIG. 1 shows the odorant receptor activity induced by validation of Accords A and B by comparison of the determined model with in vitro control experiments. [Figure 8] FIG. 13 shows agreement between flavor ratings for celery notes and sensory predictions from the model. [Figure 9] FIG. 1 shows odorant receptor activity induced by validation of Accords A, C and D by comparison with model and in vitro control experiments. [Figure 10] FIG. 13 shows the agreement between perfume ratings on Hay notes and sensory predictions from the model. [Figure 11] FIG. 1 shows agreement between fragrance ratings and sensory predictions from the model for coconut notes.

[0039] Detailed Description of the Invention This description is not exhaustive, as each feature of one embodiment may be advantageously combined with any other feature of any other embodiment.

[0040] Please note at this point that the diagram is not to scale.

[0041] The contents of US patent application Ser. No. 62 / 911,096 are incorporated herein by reference.

[0042] As used herein, the term "volatile molecule" refers to any molecule that preferably exhibits flavor or fragrance capabilities. The terms "compound" or "ingredient" refer to the same item as "volatile molecule."

[0043] The term "formula" refers to a liquid, solid or gaseous collection of at least one volatile molecule.

[0044] The term "composition" refers to the olfactory perception of a formula. A composition is defined by the perceptibility of at least one odor note.

[0045] As used herein, "olfactory note" or "olfactory note" refers to the sensory stimulant properties of volatile molecules initiated by the activation of ORs, which activity is processed by the central nervous system via the olfactory bulb, resulting in a specific experience in the subject. The experience is of a nature that the subject can describe linguistically, often with reference to the everyday object with which the olfactory experience is associated. Additional modifiers are usually required to capture the specificity of an olfactory note. Everyday objects with a characteristic "smell" usually induce the experience of multiple separable olfactory notes when evaluated by a trained expert such as a perfumer. The experience of a single olfactory note is entirely dependent on the specific ORs activated in the subject, such that a single OR generates the perception of a single olfactory note, whereas the multiple olfactory notes imparted by everyday objects are determined by the set of ORs activated by the set of volatile molecules they emit. Although the mechanisms differ in many important respects, the perception of an olfactory note can be considered analogous to the perception of a single identifiable musical note via the auditory system, which is identifiable even when multiple notes are played at once. Similarly, just as the same musical note can be described in different ways (F sharp clef, G flat clef, etc.), the same olfactory note can be described in different ways.

[0046] Non-limiting examples of olfactory notes include earthy, coconut, celery, hay, etc. (see US Patent Application No. 62 / 911,096, Example 1). For example, all OR11A1 agonists share a common earthy note, even though they induce a different overall set of scent notes (see US Patent Application No. 62 / 911,096, Example 2). A volatile molecule may have more than one scent note. For example, beta ionone has violet and blonde woody notes due to the activation of OR5A1 and OR7A17, respectively (see US Patent Application No. 62 / 911,096, Example 3).

[0047] As used herein, "aroma" refers to an olfactory perception resulting from the sum of the activation, enhancement, and inhibition (if present) of an odorant receptor by at least one volatile molecule. Thus, by way of example and not intended to limit the scope of the present disclosure in any way, an "aroma" is attributable to an olfactory perception resulting from the sum of a first volatile molecule that activates an OR associated with a coconut note, a second volatile molecule that activates an OR associated with a celery note, and a third volatile molecule that inhibits an OR associated with a hay note.

[0048] The inventors have found that activation of one OR triggers the perceivability of one odor note in a one-to-one relationship, such that a composition that is a collection of at least one odor note can be coded by a set of corresponding activated ORs, potentially with associated activation levels.

[0049] As used herein, "note" or "olfactory note" or "fragrance note" identifies an odor category. For example, floral notes include lily of the valley and violet notes.

[0050] The term "OR" or "olfactory receptor" or "odorant receptor" refers to one or more members of a family of G protein-coupled receptors (GPCRs) expressed in olfactory cells. OSNs (olfactory sensory neurons) can also be identified based on morphology or by the expression of proteins that are specifically expressed in olfactory cells. Members of the OR family may have the ability to act as receptors for olfactory signal transduction.

[0051] By "agonist of an OR" or "agonist compound" is meant a volatile compound or ligand that binds to an OR, activates the OR, and induces the olfactory receptor transduction cascade.

[0052] "Antagonist of an OR" or "antagonist compound" refers to a volatile compound or ligand that binds to an OR and reduces the measured activity of an olfactory receptor in the presence of an agonist. "Enhancer" refers to a compound or ligand that binds to an OR and enhances the activity of a receptor through the olfactory receptor transduction cascade exposed to an agonist compound when compared to the activity of the receptor exposed to an agonist compound in the absence of the enhancer. In one embodiment, a non-agonist compound binds to a site on the receptor that is different from the site to which the agonist compound binds.

[0053] "Efficacy" refers to the measure of receptor activity induced by agonist (odorant) binding in terms of the amount or concentration required to produce a given level of activity. It indicates the sensitivity of the receptor to different agonist concentrations and is often evaluated by calculating the EC50 (agonist concentration required to achieve half-maximal receptor activity).

[0054] "Efficacy" refers to a measure of the level of activity that an OR responds to a given agonist, and is obtained by measuring the activation span between constitutive activity (baseline in the absence of agonist) and agonist-induced activity.

[0055] The "receptive field" or "molecular receptive range" of an odorant receptor refers to the range of volatile compounds that activate the receptor. It represents the set of different volatile compounds that can bind to the receptor, trigger a transduction cascade within the cell, and transmit the chemical stimulus via the olfactory neuron to the brain.

[0056] "OR" or "odorant receptor" or "olfactory receptor" polypeptides belong to the seven-transmembrane domain G protein-coupled receptor superfamily encoded by a single exon approximately 1 kb long, and are considered as such if they exhibit characteristic olfactory receptor-specific amino acid motifs. The seven domains are referred to as "transmembrane" or "TM" domains TM I-TM VII, connected by three "intracellular loop" or "IC" domains IC I-IC III, and three "extracellular loop" or "EC" domains EC I-EC III. The motifs and variants thereof are defined as, but are not limited to, the presence of the MAYDRYVAIC motif (SEQ ID NO: 7) that overlaps with TM III and IC II, the FSTCSSH motif (SEQ ID NO: 8) that overlaps with IC III and TM VI, the PMLNPFIY motif (SEQ ID NO: 9) in TM VII as well as three conserved C residues in EC II and the highly conserved GN residue in TM I [Zhang, X. & Firestein, S. Nat. Neurosci. 5, 124 - 133 (2002); Malnic, B., et al. Proc. Natl. Acad. Sci. USA 101, 2584 - 2589 (2004)].

[0057] "Delivery capacity" refers to the factor that converts the amount of volatile molecules in a formula into the amount delivered to the olfactory receptors in a subject's nose.

[0058] In the context of the present invention, it should be understood that two important relationships are established: - the first relationship relating volatile molecules to the activation of ORs and - A second relationship relates the activation of ORs to specific odor notes.

[0059] In particular, a given volatile molecule may interact with several ORs, and one OR may interact with several volatile molecules. However, the activity of one OR may correspond to one perceived odor note triggered by the activity of one given OR. The perception of a single compound exhibiting several odor notes is due to the activation of several ORs that code for said odor notes. This "one-to-one" relationship is not easy to discover and has a major impact on the design of formulas and fragrances. Indeed, in a system where only the relationship between volatile molecules and odor notes is known, it is impossible to accurately predict or estimate the odor notes of a combination of volatile molecules, due to the lack of knowledge about the intermediate layers of interactions between molecules and ORs on the one hand, and ORs and odor notes on the other hand.

[0060] The first relationship can be obtained by contacting samples of volatile molecules with isolated ORs and monitoring the activity of each said OR. The results of such experiments can be stored in a database that cross-references volatile molecule digital identifiers representing the actual volatile molecules with the effects of said volatile molecules on the ORs monitored during the experiment.

[0061] In such a method, any form of OR can be used in the methods or assays described herein as long as the function of the OR is not impaired. For example, tissues or cells that endogenously express OR, such as olfactory neurons isolated from living organisms and cultures thereof, olfactory cell membranes carrying OR, recombinant cells genetically modified to express OR and cultures thereof, membranes of recombinant cells, and artificial lipid bilayer membranes carrying OR can be used.

[0062] Indicators for monitoring the activity of olfactory receptors include, for example, fluorescent calcium indicator dyes, calcium indicator proteins (e.g., GCaMP, a genetically encoded calcium indicator), fluorescent cAMP indicators, cell recruitment assays, cell dynamic mass redistribution assays, label-free cell-based assays, cAMP response element (CRE)-mediated reporter proteins, biochemical cAMP HTRF assays, β-arrestin assays, or electrophysiological recordings. In certain embodiments, a calcium indicator dye is selected that can be used to monitor the activity of olfactory receptors expressed on the membrane of olfactory neurons (e.g., Fura-2 AM). Molecules may be screened sequentially, and odorant-dependent changes in calcium dye fluorescence are measured using a fluorescent microscope or a fluorescence-activated cell sorter (FACS).

[0063] Such a method allows identification of commonalities in olfactory perception between chemically and organoleptically diverse volatile compounds based on OR activation profiles. Without intending to be limited to a particular theory, OR activation profiles represent a better predictor of the olfactory notes of a given volatile compound compared to physicochemical similarity alone. Without intending to be limited to a particular theory, physicochemical similarity may only partially predict olfactory similarity.

[0064] As an example, olfactory neurons activated by target agonists, e.g., molecules with specific olfactory notes, are isolated using either glass microelectrodes attached to a micromanipulator or a FACS machine. Mouse olfactory neurons are screened by Ca2+ imaging, similar to procedures previously described (Malnic, B., et al. Cell 96, 713-723 (1999); Araneda, RC et al. J. Physiol. 555, 743-756 (2004); and WO 2014 / 210585). In particular, the number of cells that can be screened is increased to at least 1,500 per experiment using a motorized movable microscope stage. Since mice have approximately 1,200 different olfactory receptors and each olfactory neuron expresses only one of the 1,200 olfactory receptor genes, this screening capacity will cover virtually the entire mouse odorant receptor repertoire. In other words, the combination of calcium imaging for high-throughput olfactory neuron screening leads to the identification of almost all odorant receptors that respond to a particular profile of odorants.In one embodiment, odorant receptors that respond to target agonists, for example, with a particular olfactory note, can be isolated for receptor identification.For example, at least one neuron is isolated for receptor identification.

[0065] A second relationship can be obtained by relating at least one olfactory note to an OR by screening a library of chemically and organoleptically diverse volatile compounds against the OR and identifying at least one olfactory note common to the volatile compounds that are activators of the screened OR.

[0066] Such a method of associating at least one olfactory note with an olfactory receptor can be obtained by providing an OR, contacting the OR with a volatile molecule having at least one known odor note, determining whether the compound activates the at least one olfactory receptor, repeating the contacting and determining steps with a different compound having at least one known odor note, classifying a subset of compounds that activate the OR, identifying at least one known odor note that is common to the subset of compounds, and associating the identified at least one known odor note with the OR.

[0067] The common olfactory notes of compounds that activate a given receptor can be related by comparing the overall description of the compounds and identifying common descriptors between activators.It should be understood that such olfactory notes can be semantically described in several ways, for example by perfumers.Examples of such semantic similarities that capture the same olfactory note include, for example, marine, watery and ozone; earthy, humus and moss; hay, coumarin and tonka; celery, fenugreek and maple; lily of the valley and lily of the valley.

[0068] The results of such experiments can be stored in a database that cross-references OR digital identifiers representing actual ORs with information representing the scent notes associated with activation of those ORs.

[0069] FIG. 1 shows a specific sequence of steps that are the subject of the method 100 of the present invention. This method 100 for determining the odor notes of a composition comprises the following steps: - inputting 105, on a computer interface, at least one volatile molecule digital identifier, said volatile molecule digital identifier representing an aromatic volatile molecule, said input defining a formula; - calculating 110, by the computing system, for at least one volatile molecule digital identifier of the formula, a value representing the effect of each said molecule on the activity level of an olfactory receptor, represented by an olfactory receptor digital identifier, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, said association being a many-to-many association; - determining, by the computing system, for the formula, a value representative of at least one olfactory note forming the composition as a function of the calculated influence of at least one olfactory receptor activity level and a value representative of an olfactory receptor activation threshold, wherein each olfactory receptor digital identifier is associated with one olfactory note digital identifier, said association being a one-to-one association; Includes.

[0070] The inputting step 105 can be performed using any type of computer interface, such as, for example, a keyboard, a mouse or a touch screen. Such an interface may further include a Graphical User Interface (GUI) allowing user interaction and input, said GUI being part of a software executed by a computing means such as a personal computer or a computer server. In a variant, the computer interface is logical in nature, the inputs corresponding to commands received via an electronic network or cable and emanating from a command means.

[0071] The particular architecture of the computing systems used in Figures 1-4 is not important to the present invention. That is, such computing systems may be distributed, integrated, using a client-server architecture, or using local and / or remote computing resources. Data stored and accessed may be stored in conventional databases, computer memory, or distributed databases.

[0072] During this inputting step 105, the user may select one or more volatile molecule digital identifiers to add to the formula. A volatile molecule digital identifier may be, for example, an icon, a text label or a number. Such a volatile molecule digital identifier preferably corresponds to an entry in a computer memory or database.

[0073] The formula may further include the amount of volatile molecules expressed as an amount in either the liquid, solid or gas phase. Such amounts may be expressed, for example, in parts per million (ppm) or as a measure of the headspace concentration of the gas phase of said molecules (moles / m 3 ) can be expressed as

[0074] The resulting collection of odor notes perceived from the evaporation and / or gaseous form of volatile molecules and their transport is called a composition.

[0075] The calculating step 110 is performed, for example, by a computing system configured to run dedicated software. During this calculating step 110, each input volatile molecular digital identifier is matched with a corresponding activated OR. If an OR is activated or enhanced, the effect on that OR is positive. If an OR is inactivated or its activation is inhibited, the effect on that OR is negative. One volatile molecular digital identifier may activate / enhance / inactivate / inhibit several ORs simultaneously.

[0076] This calculating step 110 may include a step of accessing an information storage device, such as a database or computer memory, in which the effect of the volatile molecular digital identifier on at least one referenced OR is stored, and retrieving said information (not shown).

[0077] Such a calculating step 110 is shown in Example 2 of US patent application Ser. No. 62 / 911,096.

[0078] The determining step 115 is carried out, for example, by a computing system configured to execute dedicated software. During this determining step 115, information is generated regarding the olfactory note associated with at least one OR activated by at least one volatile molecule. Such information may be the presence of said olfactory note or the effectiveness of said OR with respect to said olfactory note.

[0079] This is a value that represents the fragrance tone, - the perceptibility of one or more odor notes, - quantification of said perceivability, - Inhibition of the above-mentioned aroma notes, - increasing the perceptibility of the above notes and / or - Decrease in the above scent This means that it is possible to represent

[0080] This determining step 115 may include a step (not shown) of accessing an information storage device, such as a database or computer memory, in which the perfume note information to be generated is stored for at least one OR, and retrieving said information.

[0081] The determining step 115 may include calculating a value for the total activity of at least one OR, where the at least one value represents a quantification of the stored notes. Such a value may indicate, for example, whether to retrieve an associated note, the perceived intensity of the note, or the probability that the note will be perceived by the subject.

[0082] Such information may be obtained, for example, by reading said information in a suitable information storage device, or may be the result of a calculation by a computing system.

[0083] Preferably, an OR activation level threshold is used to determine the value representing the olfactory note as disclosed above. In such a variant, the activation threshold may be common for all ORs or may be determined for each OR, said threshold being empirically observed and recorded. Such a threshold is, for example, 20% of the average maximum activation level of the ORs. Such a threshold is, for example, stored in an activation threshold database used during the determining step 115.

[0084] OR activity depends on the potency and efficacy of any given agonist for this OR, obtained from receptor screening experiments. With this information, one can determine the minimum amount of material (based on efficacy data) required to generate sufficient activity (based on efficacy data) to generate the perception of the corresponding odor note. The amount of compound that inhibits or enhances the OR can be obtained from the receptor screening data as well. This quantification can be adjusted to the target outcome (presence of desired odor notes, reduction of undesired odor notes) for each OR presented in the compound mixture (or formula).

[0085] The output of the determining step 115 may be, for example, providing the result information on a computer interface, such as a computer screen.

[0086] In certain embodiments, such as that depicted in FIG. 1, the subject matter of the method 100 of the present invention includes, downstream of the calculating step 110, a step 120 of calculating, by a computing system, a total activity level for at least one olfactory receptor as a function of at least one effect on the calculated activity level.

[0087] The calculating step 120 is carried out, for example, by a computing system configured to run dedicated software. During this calculating step 120, a sum of the individual effects of the activated / enhanced / inhibited / deactivated ORs is obtained, and this result is then used to provide information during the determining step 115.

[0088] In a particular embodiment, such as the one depicted in FIG. 1, the subject of a method 100 of the invention comprises the following steps: - changing, on a computer interface, a value representative of the aroma note of the formula, step 125; - calculating 130, by the computing system, a change in the total activity level of at least one olfactory receptor; - determining 135, by the computing system, a set of at least one volatile molecule digital identifier exhibiting a total activity level impact value equal to the calculated total activity level change; - providing said set to a computer interface at a step 140; Includes.

[0089] The modifying step 125 is performed similarly to the entering step 105, for example by collecting user input via a human machine interface, said input representing a change to the value representing the fragrance note of the formula originally entered, said change being part of a formula modification command received electronically by the computing system.

[0090] A change in odor note may be a decrease in the degree to which a given odor note is perceptible or an increase in the degree to which a given odor note is perceptible.

[0091] The calculating step 130 is carried out, for example, by a computing system configured to execute dedicated software. During this calculating step 130, a modification affecting at least one olfactory note is converted into a modification of the activity level for the underlying OR or ORs.

[0092] The determining step 135 is performed, for example, by a computing system configured to run dedicated software. During this determining step 135, the change in activity level for the OR or ORs calculated during the calculating step 130 is translated into a change in the input of volatile molecules that activate / enhance / inhibit / inactivate said OR or ORs.

[0093] It should be understood that the total activity level impact value, which is equal to the calculated total activity level change, is understood as a value lying within an interval representing an acceptable deviation from the exact equation.

[0094] Such changes may: - removal of volatile molecules from the formula (which translates into removal of the corresponding digital identifiers from the formula), - the addition of a volatile molecule to the formula (which translates into the addition of a corresponding digital identifier from the formula) and / or - Change in the amount of volatile molecules in the formula (which is translated into a change in the index that represents the amount of the corresponding digital identifier in the formula) It can correspond to.

[0095] Given the fact that there is a many-to-many relationship between volatile molecules and the impact of OR activity, and a one-to-one relationship between the impact of OR activity and odor note perceptibility for each OR and the corresponding odor note, there are several combinatorial solutions for the calculating step 130 and the determining step 135.

[0096] In order to determine the optimal solution of these steps, an optimization solution rule is preferably put in place. Such a solution rule may be: - a first rule, wherein the determined set of at least one volatile molecular digital identifier is configured to present a minimum number of volatile molecular digital identifiers; - a second rule, in which the determined set of at least one volatile molecular digital identifier is configured to present a minimum total quantity indicator of the corresponding volatile molecular digital identifier; - a third rule, wherein the determined set of at least one volatile molecular digital identifier is configured to present a minimum number of adversely affecting volatile molecular digital identifiers; - a fourth rule, according to which at least one volatile molecule digital identifier is associated with a volatile molecule deliverability indicator, said rule being configured to match the determined set of at least one volatile molecule digital identifier as a function of said volatile molecule deliverability indicator for the volatile molecule digital identifiers in the set; - a fifth rule, wherein the set of at least two volatile molecular digital identifiers is configured to minimize the overlap of odorant receptors activated by said set of molecules; - a sixth rule, wherein the set of at least two volatile molecular digital identifiers is configured to minimize modulation of odorant receptors activated by the set of molecules; - a seventh rule, wherein the determined set of at least one volatile molecular digital identifier is configured to maximize the negative modulation or inhibition of odorant receptors associated with a given undesirable olfactory note; - an eighth rule, wherein the determined set of at least one volatile molecular digital identifier is configured to maximize a positive modulation or enhancement of an odorant receptor associated with a predetermined desired olfactory note; and / or - A ninth rule, wherein the determined set of at least one volatile molecule digital identifier is configured to minimize or maximize at least one cost function, and each volatile molecule is associated with at least one value representing a cost.

[0097] The fourth rule may represent the availability of volatile molecules in the headspace to produce the desired level of activation. This rule accounts for non-linear factors associated with the delivery of the composition that affect the amount that reaches the OR. Examples of these factors include deposition onto the substrate, evaporation from the substrate, rate of sorption into mucus, transport by dedicated molecules in mucus, and biodegradation of the molecule in mucus.

[0098] In certain embodiments, at least one volatile molecule digital identifier is associated with a volatile molecule delivery capability index, and the calculating step 110 is performed as a function of the volatile molecule delivery capability index associated with the at least one input volatile molecule digital identifier.

[0099] The volatile molecule deliverability index is stored in a volatile molecule deliverability index database and is, for example, empirically determined.

[0100] In one example, to determine a deliverability index, a formula containing at least one volatile molecule is administered at a predetermined concentration to a relevant substrate, such as fabric, bare skin, kitchen tile, cat litter, etc., or aerosolized directly into the air and placed under relevant environmental conditions, such as in a chamber of constant temperature, pressure and humidity, and allowed to sit for a relevant period of time. A known volume of air in the chamber is sampled for a known period of time by a suitable device, such as a sorbent tube or fiber, which can then be analyzed by a quantitative chemical analyzer, such as a gas chromatography mass spectrometer, to determine the gas phase concentration of the at least one molecule.

[0101] In another example, a known gas phase concentration of at least one volatile molecule representative of the formula can be established over a period of time under appropriate pressure, temperature and humidity in a suitable chamber that includes an interface of known surface area with a known volume of liquid phase substrate, such as mucus, The concentration of the at least one molecule can then be determined by applying a sample of the liquid phase substrate to a quantitative analytical chemistry device, such as a liquid chromatography mass spectrometer.

[0102] In a third example, calculation of more complex deliverability indices is possible by combining the previous two examples and / or by measuring physicochemical constants such as Henry's constants by established methods and combining them with relevant physical models.

[0103] The calculating step 110 may for example be configured to calculate losses due to a molecular deliverability index, said losses affecting the value representative of the odour note determined in the determining step 115 .

[0104] In embodiments where a value representative of an odor note is set, the determining step 135, 155 or 165 may be performed as a function of the molecular deliverability index. In such embodiments, a loss in the molecular deliverability index for a given volatile molecular digital identifier may be compensated for, for example, by increasing the amount of said volatile molecule in the formula.

[0105] In certain embodiments, the volatile molecule delivery capability index is representative of the substrate on which the associated volatile molecule is disposed.

[0106] Such substrates may be, for example, fabric types, food types, or the absence of such substrates, such as the aerosolization of fragrances into the air.

[0107] Additional rules relating to external parameters may be in place. In a variant, each volatile molecular digital identifier is associated with a cost, which may be environmental, economic or other cost.

[0108] In a first example of such an additional rule, the corresponding rule may be that the determined set of at least one volatile molecular digital identifier is configured to exhibit a minimum cost value.

[0109] In a second example of such an additional rule, the corresponding rule may be that the determined set of at least one volatile molecular digital identifier is configured to exhibit a cost value inferior or superior to a predetermined threshold.

[0110] In a third example of such an additional rule, the corresponding rule may be that the determined set of at least one volatile molecular digital identifier is configured to exhibit a minimum sum of cost values, where at least two types of cost are taken into account.

[0111] The step 140 of providing the result of the step 135 of determining corresponds to the step 140 of providing described above.

[0112] In a particular embodiment, such as the one shown in FIG. 1, each scent note is associated with a scent note digital identifier, and the method includes a step 145 of automatically selecting a scent note as a function of the result of comparing the scent note digital identifier of the formula with a set of at least one predefined scent note digital identifier, and the step 125 of modifying the value representative of the scent of said selected scent note identifier of the formula is configured to set the value of said selected scent note identifier to a reduced value, preferably zero.

[0113] The step 145 of automatically selecting scent notes is carried out, for example, by a computing system configured to execute dedicated software. In this step 145 of automatically selecting scent notes, the objective is to remove unpleasant scent notes from the composition. Such unpleasant scent notes may correspond to certain predetermined scent note identifiers stored in a computer memory or database. During this step 145 of automatically selecting scent notes, the scent notes determined during the step 115 of determining may be matched against predetermined unpleasant scent note identifiers, and during the step 125 of modifying, at least one of the matched scent notes may be modified, set to a reduced value, preferably zero.

[0114] In a particular embodiment, such as that shown in FIG. 1, the method 100 of the present invention is the subject of the following steps: - selecting 150, on a computer interface, a volatile molecular digital identifier of the formula; - determining 155, by the computing system, at least a set of at least one volatile molecule digital identifier that exhibits a value representing an effect on the activity level of the olfactory receptor equal to a value representing an effect of the selected volatile molecule digital identifier on the activity level of the olfactory receptor; - providing said set to a computer interface at a step 140; Includes.

[0115] The selecting step 150 is performed in a similar manner as, for example, the entering step 105. This selecting step 150 can be performed manually or automatically, as a result of a selection command sent to a computing system. The selection criteria can be arbitrary or can follow an algorithmic solution based on information associated with each volatile molecular digital identifier, such as a cost value for each volatile molecular digital identifier.

[0116] The determining step 155 is performed, for example, by a computing system configured to run dedicated software. This determining step 155 can be performed in a similar manner to the determining step 135 described above. Such determining step 155 may follow optimization rules as described above.

[0117] This determining step 155 allows for the replacement of a volatile molecule in the formula by at least one other volatile molecule represented by a corresponding digital identifier or digital identifiers.

[0118] The step 140 of providing the result of the step 155 of determining corresponds to the step 140 of providing described above.

[0119] In a particular embodiment, such as that shown in FIG. 1, the method 100 of the present invention is the subject of the following steps: - a step 160 of selecting at least two volatile molecule digital identifiers of the formula, said at least two volatile molecules being associated with the activation of at least two different olfactory receptors, called "target receptors"; - determining 165 one volatile molecule digital identifier that exhibits a value representative of the effect on the activity level of each target receptor equal to the value representative of the effect of the selected volatile molecule digital identifier on the activity level of said olfactory receptor; - providing 140 the determined volatile molecular digital identifier to a computer interface; Includes.

[0120] Such an embodiment aims to simplify the formula with respect to the number of volatile molecules used.

[0121] The selecting step 160 is performed in a similar manner as, for example, the entering step 105. This selecting step 160 can be performed manually or automatically, as a result of a selection command sent to a computing system. The selection criteria can be arbitrary or can follow an algorithmic solution based on information associated with each volatile molecular digital identifier, such as a cost value for each volatile molecular digital identifier.

[0122] The determining step 165 is carried out, for example, by a computing system configured to execute dedicated software. This determining step 165 is designed to select a volatile molecule digital identifier that plays the same role as the at least two volatile molecule digital identifiers selected during the selecting step 160. Role in this context is defined by the influence of said volatile molecule on at least two ORs. In other words, the OR influence signature of the identified volatile molecule should correspond to the OR influence signature of the selected volatile molecule.

[0123] This determining step 165 may follow optimization rules such as those described above for the other determining steps, 135 or 155 .

[0124] The step 140 of providing the result of the step 165 of determining corresponds to the step 140 of providing described above.

[0125] In certain embodiments, such as that shown in FIG. 1, the subject matter of the method 100 of the present invention includes, downstream of the determining step 135, 155 or 165, a step 170 of estimating an amount for at least one of said volatile molecular digital identifiers, said amount being used in the downstream step 140 of providing.

[0126] The estimating step 170 is performed, for example, by a computing system configured to execute dedicated software. This estimating step 170 uses, for example, an influence function that relates the amount of volatile molecules to the activity level of the OR. Said influence function may be generic for all volatile molecules or may be specific for each volatile molecule.

[0127] Volatile molecules can compete for odorant receptor binding and subsequently activate the receptor, in which case the relative amounts of the molecules, their respective binding coefficients and propensity to induce activation determine the total activation of the OR.

[0128] A single molecule that activates an OR does so with a sigmoidal dependence on the logarithm of the concentration of the molecule in contact with the receptor. To determine the dependence, one skilled in the art can contact a given molecule at different concentration levels and record the activation level of the OR. By determining the range of activation levels of the OR by increasing the concentration of the molecule, and using a sigmoidal fit function, a resulting formula can be obtained to estimate the resulting activation level of the OR from any concentration value.

[0129] Multiple molecules that activate an OR do so as a nonlinear function of the ratio of their binding coefficients, the logarithm of the concentration of the molecular species, and their individual propensities to activate the receptor. In another mode of operation, two or more volatiles may bind to the receptor noncompetitively and unidirectionally or mutually affect the binding affinity and / or activation propensity of the other binding molecules. The total activity of the receptor is then a nonlinear combination of the logarithm of the concentration, the binding coefficient, the activation propensity, and the modulation coefficients of the binding coefficient and activation propensity. In all these cases, the resulting total activity can be measured directly in an experimental assay and used to determine a function relating the amount of volatile molecule to the total activity.

[0130] Such a function is used by regression to determine the amount of the corresponding volatile molecule from the determined effects.

[0131] Such an embodiment may trigger additional optimization rules based on the amount of volatile molecules as described above.

[0132] In certain embodiments, such as that shown in FIG. 1, the subject matter of the method 100 of the present invention includes a step 175 of inputting an amount of at least one input volatile molecule on a computer interface, said amount being used by the computing system in a step 110 of calculating a value representing the effect on the activity level of an olfactory receptor for at least one volatile molecule digital identifier of the formula.

[0133] The inputting step 175 is for example carried out in a similar manner as the inputting step 105. In the inputting step 175 of a value representative of the amount of input molecules, during the inputting step 105 a numerical value is input, said value being representative of the amount of said volatile molecules.

[0134] The calculating step 110 may use an influence function that relates the amount of a volatile molecule to the activity level of an OR. Said influence function may be general for all volatile molecules or may be specific for each volatile molecule. The amount entered makes it possible to calculate the influence of said volatile molecule, which in turn makes it possible to determine the degree of perceptibility of the olfactory note of the formula.

[0135] 2 shows a particular sequence of steps of the subject of the method 100 of the invention. This formula determination method 200 comprises the following steps: - a step 205 of inputting, on a computer interface, for at least one fragrance note digital identifier, a value representative of the fragrance note of the composition derived from the formula to be determined; - determining 210, by the computing system, for the formula to be determined, a value of an olfactory receptor activity level for at least one olfactory receptor digital identifier representing an olfactory receptor as a function of at least one value representing at least one olfactory note of said composition, wherein each olfactory receptor digital identifier is associated with one olfactory note digital identifier, said association being a one-to-one association; - determining 215 a formula represented by at least a set of at least one volatile molecule digital identifier that presents a value representing an effect on the activity level of the olfactory receptor digital identifier equal to a determined value representing the activity level on the olfactory receptor, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, the association being a many-to-many association; Includes.

[0136] The input step 205 is carried out in a similar manner to the input step 105 described with reference to figure 1. This step can be manual or automatic, depending on the use of the invention. During this input step 205, instead of inputting a volatile molecular identifier as in figure 1, a fragrance note digital identifier is input. Such fragrance note digital identifier can correspond to the presence of a fragrance note in the formula, or to the degree of perceptibility of said fragrance note.

[0137] The determining step 210 is performed, for example, by a computing system configured to execute dedicated software. This determining step 210 is configured to perform the reverse of the determining step 115 of Fig. 1, and can determine the impact on OR activity from the input of a given scent note identifier. This determining step 210 functions similarly to the step 130 of calculating the change in total activity level, but is not limited to only the change, but rather the entire impact evaluation.

[0138] The determining step 215 is performed, for example, by a computing system configured to execute dedicated software. This determining step 215 functions in a similar manner to the determining step 135.

[0139] The output of the determining step 215 may be a computer interface. Such output is similar to the providing step 140 disclosed with respect to FIG.

[0140] In certain embodiments, the providing step 140 is configured to provide corresponding data to a corresponding actuator, such as a formula assembly means configured to assemble a formula corresponding to the volatile molecules provided in the determined amount (or standard amount). In such embodiments, the assembly means may comprise a sample of the volatile molecules and a reactor configured to receive all or a portion of said sample, and the volatile molecules are provided to the reactor as a function of a formula derived from the method, 100 or 200.

[0141] FIG. 3 shows a particular embodiment of the subject matter of the present invention, a system 300. This composition odor determination system 300 comprises: - means 305 for inputting at least one volatile molecule digital identifier, said volatile molecule digital identifier representing a fragrance volatile molecule, said input defining a formula; and - means 310 for calculating, for at least one volatile molecule digital identifier of the formula, a value representing the effect of the activity level of each said molecule on the activity level of an olfactory receptor, as represented by an olfactory receptor digital identifier, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, said association being a many-to-many association; - determining, for the composition, a value representative of at least one olfactory note forming the composition as a function of the effect of the at least one calculated olfactory receptor activity level and a value representative of an olfactory receptor activation threshold, wherein each olfactory receptor digital identifier is associated with one olfactory note digital identifier, said association being a one-to-one association; and Equipped with.

[0142] Particular embodiments of the means of system 300 have been described with reference to the functional steps performed in the description of Figures 1 and 2 above.

[0143] The means for inputting 305 is, for example, a keyboard, a mouse and / or a touch screen adapted to interact with the computing system in such a way as to collect user input. In a variant, the means for inputting 305 is logical in nature, such as a network port of the computing system configured to receive electronically transmitted input commands. Such an inputting means 305 can be associated with a GUI or an API (Application Programming Interface) that is presented to the user.

[0144] The means for calculating 310 and the means for determining 315 may for example be computing systems configured to execute dedicated software in charge of executing the corresponding algorithms.

[0145] FIG. 4 illustrates a particular embodiment of the subject matter of the present invention, a system 400 for determining a fragrance formula. The system 400 includes: - means 405 for inputting, on a computer interface, for at least one fragrance note digital identifier, a value representative of the fragrance note of the composition derived from the formula to be determined; - means 410 for determining, by a computing system, for a formula to be determined, a value of an olfactory receptor activity level for at least one olfactory receptor digital identifier representing an olfactory receptor as a function of at least one value representing at least one olfactory note of said composition, wherein each olfactory receptor digital identifier is associated with one olfactory note digital identifier, said association being a one-to-one association; - determining a formula represented by at least a set of at least one volatile molecule digital identifier that exhibits a value representing an effect on the activity level of the olfactory receptor digital identifier equal to a determined value representing an activity level on the olfactory receptor, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, the association being a many-to-many association; and Equipped with.

[0146] The means for inputting 405 is similar to the means for inputting 305 described with reference to FIG.

[0147] The means for determining 410 and the means for determining 415 may for example be computing systems configured to execute dedicated software in charge of executing the corresponding algorithms.

[0148] It should be understood from the above that a formula defined by the selection of at least one volatile molecule can be coded into a set of activated OR indices, said ORs corresponding to perceived odor notes. Such a coding system offers several applications in terms of formula optimization or performance prediction. Figures 5-11 provide an example of modeling OR activity and its impact on odor note prediction.

[0149] As an example, in FIG. 5, a fragrance accord (Accord A) containing ingredients that activate the odorant receptors OR8B3 (resulting in a hay note), OR8D1 (resulting in a celery note) and OR5AU1 (resulting in a lactonic coconut note) is shown together with three accords with minor modifications (Accords B-D). Ingredients that do not activate any of the three target ORs are aggregated for simplicity and listed as "other ingredients" in FIG. 5. Using the receptor screening data for each OR (described in Example 1 of US Patent Application No. 62 / 911,096), alternative activators can be substituted for ingredients present in the original formula. This approach allows for prioritizing the use of preferred ingredients to optimize multiple factors, including cost reduction, increased biodegradability, or the use of compounds with environmentally friendly properties.

[0150] Using this computing system, the total receptor activity levels of the Accords shown in Figure 5 were determined from a nonlinear combination of empirically determined information on the individual volatile molecules shown in Figure 6, and were verified to match the empirical mixed responses shown in Figures 7 and 9. The activity levels can be normalized to the maximum cellular response to forskolin, a known pharmacological transduction cascade activator, to serve as an anchor point for data comparison. The Accord activity predicted by the model was compared to cell-based data generated with the same Accords (cell-based assay described in Example 2 of US Patent Application 62 / 911,096). Concordant activity levels were observed between the model and the in vitro data, confirming that the model is valid. The resulting activity predictions between the original and modified Accords were used to make sensory predictions based on the change in OR activity (i.e., more or less active) and to infer the corresponding change in odor note (i.e., stronger or weaker). The sensory predictions were validated by a sensory panel of fragrance experts who were asked to perform a blind evaluation of the three target odor notes for each accord: hay, celery and lactonic coconut.

[0151] With regard to OR8D1 activity, the case of a composition in which cyclotene was removed and replaced by maple furanone is shown in Figure 5 (compare Accords A and B). The target activity level was set such that OR8D1 was lower than its original activity level. Figure 7 shows the predicted activity levels from the model compared to the in vitro validation of the receptor, normalized to a 100% forskolin response. A corresponding reduction in the perception of celery tones was predicted, which was confirmed by the expert panelists' evaluation, as summarized in Figure 8.

[0152] The case of a composition in which nonalactone was removed and replaced with coumarin, with respect to OR8B3 and OR5AU1 activity, is shown in Figure 5 (compare Accords A and C). In this case, the target activity level was set for OR8B3 to be higher than the original activity level and for OR5AU1 to be null relative to the original activity level. Figure 9 shows the predicted activity levels from the model compared to the in vitro validation of both receptors, normalized to a 100% forskolin response. A corresponding increase in the perception of hey tone and a corresponding loss of lactonic coconut tone was predicted, which was confirmed by the expert panelists' evaluation, as summarized in Figure 10.

[0153] The case of compositions where nonalactone was replaced by coumarin and tuberolide was added resulting in the desired OR8B3 and OR5AU1 activity is shown in Figure 5 (compare Accords A, C and D). Target activity levels were set to be the same for Accord D vs Accord C for OR8B3, and for OR5AU1, Accord D restored to the level of Accord A. Figure 9 shows predicted activity levels from the model compared to in vitro validation of both receptors, normalized to 100% forskolin response. A corresponding restoration of the perception of coconut tone with restored OR5AU1 activity was predicted along with a maintenance of increased perception of hay tone, which was confirmed by expert panelist evaluation, as summarized in Figure 11.

[0154] These examples of modification of fragrance accords capture the ability of the system to model the receptor activity of complex mixtures before and after compound removal and replacement using only single compound input data (obtained in Examples 1-3 of US Patent Application Serial No. 62 / 911,096). The ability of the system to predict sensory outcomes based on calculated or measured receptor activity allows the use of different compositions to maintain the perception of a particular desired odor note, adjusting the compound concentrations or ratios in the mixture to reduce or increase the desired odor note, and adding compounds to rebalance the composition by restoring the desired odor note lost during modification. As will become clear from these examples, a set of desired perceived odor notes can be set in the computing system (representing the target odor notes) and a set of compounds and their concentrations that will result in the required total OR activity can be determined, or conversely, compositions can be modified as required and their effect on the resulting perceived odor note determined by calculating the resulting OR activity, or even further, a set of desired or measured receptor activity levels can be input to calculate both the resulting perceived odor notes and a plausible set of compositions.

Claims

1. A method for determining a composition's fragrance note (100) comprising the steps of: - inputting (105) on a computer interface at least one volatile molecule digital identifier, said volatile molecule digital identifier representing an aromatic volatile molecule, said input defining a formula; - calculating (110) by a computing system, for at least one volatile molecule digital identifier of said formula, a value representing the effect of each said molecule on the activity level of an olfactory receptor, represented by an olfactory receptor digital identifier, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, said association being a many-to-many association; - determining (115) by the computing system, for said formula, a value representative of at least one olfactory note forming the composition as a function of the calculated influence of at least one olfactory receptor activity level and a value representative of an olfactory receptor activation threshold, wherein each olfactory receptor digital identifier is associated with one olfactory note digital identifier, said association being a one-to-one association; A method (100), comprising:

2. The method (100) of claim 1 further comprises, downstream of the calculating step (110), a step (120) of calculating, by a computing system, a total activity level for at least one olfactory receptor as a function of at least one effect on the calculated activity level.

3. Steps below: - modifying (125) on a computer interface a value representative of the scent note of said composition; - calculating (130) by a computing system the change in the total activity level of at least one olfactory receptor; - determining (135) by the computing system a set of at least one volatile molecule digital identifier that exhibits a total activity level impact value equal to the calculated total activity level change; - providing (140) said set to a computer interface; The method (100) of claim 1 or 2, comprising:

4. 4. The method (100) of claim 3, wherein each scent note is associated with a scent note digital identifier, the method comprising a step (145) of automatically selecting a scent note as a function of a result of comparing the scent note digital identifier of the composition with a set of at least one predefined scent note digital identifier, and the step (125) of changing the value representing the scent of the selected scent note identifier of the composition is configured to set the value of the selected scent note identifier to a reduced value, preferably zero.

5. The value representing the effect of a molecule on the activity level of an odorant receptor, as represented by a volatile molecular digital identifier, - activation of said odorant receptors, - inactivation of said odorant receptors, - enhancement of said odorant receptors and / or - inhibition of said odorant receptors The method (100) of any one of claims 1 to 4, wherein:

6. The method (100) of claim 5, which cites claim 3 or 4, wherein the determining step (135) is configured to provide at least one volatile molecule digital identifier that presents a value representative of an effect on the activity of an olfactory receptor associated with the fragrant note changed during the changing step (125), the effect corresponding to either an enhancement of the olfactory receptor or an inhibition of the olfactory receptor.

7. Steps below: - selecting (150) on a computer interface a volatile molecular digital identifier of said formula; - determining (155) by a computing system a set of at least one volatile molecule digital identifier that exhibits a value representing an effect on the activity level of an olfactory receptor equal to a value representing an effect of the selected volatile molecule digital identifier on the activity level of the olfactory receptor; - providing (140) said set to a computer interface; The method (100) of any one of claims 1 to 5, comprising:

8. Steps below: - selecting (160) at least two volatile molecule digital identifiers of said formula, said at least two volatile molecules being associated with the activation of at least two different olfactory receptors, called "target receptors"; - determining (165) one volatile molecule digital identifier that exhibits a value representative of the effect on the activity level of each target receptor equal to the value representative of the effect of the selected volatile molecule digital identifier on the activity level of the olfactory receptor; - providing (140) said determined volatile molecular digital identifier to a computer interface; The method (100) of any one of claims 1 to 7, comprising:

9. The method (100) of any one of claims 3 to 8, further comprising a step (170) of estimating an amount for at least one of the volatile molecular digital identifiers downstream of any of the determining steps (135, 155, 165), the amount being used in a downstream step (140) of providing.

10. The step of determining (135, 155) at least a set of at least one volatile molecular digital identifier by the computing system is performed according to the following rules: a first rule, in which the determined set of at least one volatile molecular digital identifier is configured to present a minimum number of volatile molecular digital identifiers; a second rule, in which the determined set of at least one volatile molecular digital identifier is configured to exhibit a minimum total quantity index of the corresponding volatile molecular digital identifiers; a third rule, in which the determined set of at least one volatile molecular digital identifier is configured to present a minimum number of adverse volatile molecular digital identifiers; a fourth rule, according to which at least one volatile molecule digital identifier is associated with a volatile molecule deliverability index, said rule being configured to match the determined set of at least one volatile molecule digital identifier as a function of said volatile molecule deliverability index for the volatile molecule digital identifiers in the set; A fifth rule, wherein the set of at least two volatile molecular digital identifiers is configured to minimize the overlap of odorant receptors activated by the set of molecules; a sixth rule, wherein the set of at least two volatile molecular digital identifiers is configured to minimize the modulation of the olfactory receptors activated by the set of molecules; - a seventh rule, wherein the determined set of at least one volatile molecular digital identifier is configured to maximize the negative modulation or inhibition of odorant receptors associated with a given undesirable olfactory note; an eighth rule, wherein the determined set of at least one volatile molecular digital identifier is configured to maximize a positive modulation or enhancement of an odorant receptor associated with a predetermined desired olfactory note; and / or A ninth rule, in which the determined set of at least one volatile molecule digital identifier is configured to minimize or maximize at least one cost function, and each volatile molecule is associated with at least one value representing a cost. The method (100) of any one of claims 3 to 9, further comprising: executing an optimization rule, the optimization rule being at least one of:

11. A method (100) as described in any one of claims 1 to 10, comprising a step (175) of inputting an amount of at least one input volatile molecule on a computer interface, said amount being used by a computing system in a step (110) of calculating a value representing the effect on the activity level of an olfactory receptor for at least one volatile molecule digital identifier of the formula.

12. 12. The method (100) of any one of claims 1 to 11, wherein at least one volatile molecule digital identifier is associated with a volatile molecule delivery capability index, and at least one of the calculating (110) and determining (135, 155, 165) steps is performed as a function of the volatile molecule delivery capability index associated with at least one input volatile molecule digital identifier.

13. The method (100) of claim 12, wherein the volatile molecule delivery capability index is representative of a substrate on which the associated volatile molecule is disposed.

14. The method (200) for formula determination comprises the following steps: - inputting (205), on a computer interface, for at least one fragrance note digital identifier, a value representative of the fragrance note of the composition derived from the formula to be determined; - determining (210) by a computing system, for the formula to be determined, a value of an olfactory receptor activity level for at least one olfactory receptor digital identifier representing an olfactory receptor as a function of at least one value representing at least one olfactory note of the composition, wherein each olfactory receptor digital identifier is associated with at least one olfactory note digital identifier, said association being a one-to-one association; - determining (215) a formula represented by at least a set of at least one volatile molecule digital identifier that presents a value representing an effect on the activity level of the olfactory receptor digital identifier equal to a determined value representing the activity level on the olfactory receptor, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, the association being a many-to-many association; A method (200), comprising:

15. In the system (300) for determining the composition fragrance note, the following means are provided: - means (305) for inputting at least one volatile molecule digital identifier, said volatile molecule digital identifier representing a fragrant volatile molecule, said input defining a formula; - means (310) for calculating, for at least one volatile molecule digital identifier of said formula, a value representing the effect of the activity level of each said molecule on the activity level of an olfactory receptor, represented by an olfactory receptor digital identifier, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, said association being a many-to-many association; - means (315) for determining, for said composition, a value representative of at least one olfactory note forming said composition as a function of the effect of at least one calculated olfactory receptor activity level and a value representative of an olfactory receptor activation threshold, wherein each olfactory receptor digital identifier is associated with one olfactory note digital identifier, said association being a one-to-one association; A system (300) comprising:

16. In the system (400) for formula determination, the following means are provided: means (405) for inputting, on a computer interface, for at least one digital odor note identifier, a value representative of the odor note of the composition resulting from the formula to be determined; - means (410) for determining, by a computing system, for the formula to be determined, a value of an olfactory receptor activity level for at least one olfactory receptor digital identifier representing an olfactory receptor as a function of at least one value representing at least one olfactory note of the composition, wherein each olfactory receptor digital identifier is associated with one olfactory note digital identifier, said association being a one-to-one association; - means (415) for determining a formula represented by at least a set of at least one volatile molecule digital identifier that presents a value representative of an effect on the activity level of the olfactory receptor digital identifier equal to a determined value representative of the activity level on the olfactory receptor, wherein each volatile molecule digital identifier is associated with at least one olfactory receptor digital identifier, the association being a many-to-many association; and A system (400) comprising:

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