Patent Publication Number: US-2022233686-A1

Title: Epitope-Based Approach for Allergy Treatments and Inhibitors for Crohn&#39;s Disease

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application claims the benefit of U.S. Provisional Patent Application No. 62/817,564 filed Mar. 13, 2019 entitled “Epitope-Based Approach For Virulence Factors And/Or Food Allergy Treatments And Detection Methods, Systems, And/Or Therapeutics”; U.S. Provisional Patent Application No. 62/817,621 filed Mar. 13, 2019 entitled “Epitope-Based Approach As A Detection And/Or Treatment Method, System, And/Or Therapeutic Composition For Peanuts Allergy And/Or Related Dietary Food”; U.S. Provisional Patent Application No. 62/824,095 filed Mar. 26, 2019 entitled “Unlocking The Microbiome For New Opportunities In Drug Discovery”; U.S. Provisional Patent Application No. 62/828,074 filed Apr. 2, 2019 entitled “Design Of Inhibitors Of Crohn&#39;s Disease-Associated I2 Superantigen And MHC-II”; U.S. Provisional Patent Application No. 62/832,811 filed Apr. 11, 2019 entitled “Unlocking The Microbiome For New Opportunities In Drug Discovery”, all of which are incorporated by reference herein in their entirety. 
    
    
     SEQUENCE LISTING SUBMISSION VIA EFS-WEB 
     A computer readable text file, entitled “SequenceListing.txt,” created on May 14, 2020 with a file size of 57,696 bytes contains the sequence listing for this application and is hereby incorporated by reference in its entirety. 
     BACKGROUND 
     Food allergy can include an hypersensitive immune response caused by a food exposure, particularly an agent, typically a protein. The origin of food allergy is unknown. Some proposal factors are genetic, excessive hygiene, geographical factors, amongst others. 
     Products which are used to treat diseases derived from allergens and pathogens, usually take advantage of the classic concept of a vaccine which has been developed to resemble the natural pathogen. Some treatments include some antigenic components typical of a pathogen or allergen; in other cases the components used had been inactivated, weakened and/or mimicked. Subcutaneous immunotherapy, recombinant vaccines, oral immunotherapy (OIT) and probiotics sublingual immunotherapy, are recent approaches reported to treat food allergy. 
     However, the microbiome can play an important role in preventing food allergy, and/or stimulating an adverse reaction. Epitopes, have been described as a valuable tool, to develop new methods against the pathogens, allergy or infectious agents and particularly epitope-based vaccines are intended to trigger an immune response through different proteins from a pathogen or allergen, and are focused on some specific short amino acid sequences which can be isolated to be rationally modified. The ability to rationally modify the sequence of epitopes aimed by in-silica tools can result in an increase or decrease, in the activity of those epitopes, which otherwise would not trigger an optimal immunity response. In this regard, an epitope can be a fragment derived from an antigen, which can be recognized by antibodies or immune cells, such as B or T cells. Epitopes from protein antigens can be classified into conformational or linear epitopes. Conformational epitopes are composed of discontinuous sections of a protein, meanwhile linear epitopes are formed by a continuous sequence of amino acids from an antigen. 
     Identification of potential T-cell epitopes in the food allergens can be important for development of peptide-based immunotherapy. Traditional methods to identify T-cell epitopes from allergens use overlapping short peptides spanning a full-length protein. However, this approach can be expensive because many peptides must be tested. 
     Peanut allergy is the most common food allergy and one of the causes of food-induced anaphylaxis; a sudden and potentially deadly condition that requires immediate attention and treatment, especially among school-aged children in the United States. Symptoms of anaphylaxis include impaired breathing, swelling in the throat, drop in blood pressure, pale skin or blue lips, fainting and dizziness. Anaphylaxis can be fatal unless treated immediately with epinephrine(adrenaline). 
     In recent years the number of peanut allergy cases reported has risen. In May 2010, a study noted that the rate of peanut allergies in children had more than tripled between 1997 and 2008. Thus, avoiding peanut and peanut-derived products and/or treatment with adrenaline are the only methods to prevent the allergy. 
     Recent approaches reported to treat peanut allergy include subcutaneous immunotherapy, oral immunotherapy (OIT), and probiotics sublingual immunotherapy. However, those approaches include using crude peanut extract (CPE) which may cause life-threatening anaphylactic reactions or low efficacy. 
     Differently, T-cell epitopes-based immunotherapy lacks of these disadvantages, providing desensitization avoiding secondary effects, because those epitopes are too short to induce cross-linking to allergen-specific IgE on basophils or mast cells, like CPE can do. This strategy was designed based on experimental results that demonstrated that tolerance against a complete allergen can be induced using small allergen-derived peptides, which are recognized by allergen specific T cells. Thus, it has been described that cocktails of defined epitopes or chimeric protein arrangements including the target epitopes can elicit convenient humoral or cellular immune responses. 
     Identification of potential T-cell epitopes in the peanut major allergens is essential for development of peptide-based immunotherapy. Traditional methods to identify T-cell epitopes from allergens use overlapping short peptides spanning a full-length protein, such as Arahl. However, this approach can be expensive because many peptides must be tested. 
     Crohn&#39;s disease (CD) is a type of inflammatory bowel disease, which can be associated with an abnormal immune system response that causes chronic inflammation in the digestive tract. Common symptoms of CD include abdominal pain, severe diarrhea, fatigue, loss of appetite, fever, cramping and weight loss. Complications of the disease can also cause ulcers within the intestines, fissures in the lining of the anus, increased risk of colorectal cancer, and development of chronic health conditions, including cardiovascular disease, respiratory disease, cancer, arthritis, kidney and liver diseases. CD is more frequently diagnosed in young adults. Family history and cigarette smoking could be risk factors in the development of Crohn&#39;s disease. 
     The causes of CD remain unknown, however genetic and environmental factors play significant roles in the pathogenesis. Evidence suggests that commensal bacteria is important in pathogenesis, and therefore bacteria can trigger immune activation in CD. Studies have identified a novel microbial T-cell superantigen I2 from  Pseudomonas fluorescens  that is involved in the pathogenesis of CD. The superantigen interacts with human MHC class 11 HLA-DR producing a non-specific activation of T-cells, which leads to activation of a large number of T-cells and to a massive cytokine release, and leading to a greater frequency of strictures, internal perforations, and/or other complications, which can require a small bowel surgery for treatment. The binding between I2 T-cell superantigen (implicated in the pathogenesis of Crohn&#39;s disease) and Human MHC Class 11 leads to a massive cytokine release and a large number of T-cells activation, which produce a greater frequency of strictures, internal perforations and small bowel surgery. 
     BRIEF SUMMARY OF THE DISCLOSURE 
     In some embodiments, the present disclosure relates to a peptide for treating an allergy comprising a sequence of X 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 X 13 X 14 X 15  (SEQ ID NO: 1); wherein:
         X 1  is E;   X 2  is E or T;   X 3  is Q or P;   X 4  is G;   X 5  is A or W;   X 6  is I;   X 7  is V;   X 8  is T;   X 9  is V;   X 10  is K;   X 11  is G or Q;   X 12  is G;   X 13  is L;   X 14  is R; and   X 15  is I, H or W.       

     In some embodiments, the present disclosure relates to a peptide comprising a sequence of X 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 X 13 X 14 X 15  (SEQ ID NO: 2); wherein:
         X 1  is N, A, C, D, F, G, H, L, M, P, R, S, T, W, or Y;   X 2  is Y, C, F, G, H, L, M, N, T, V, or W;   X 3  is A, C, E, F, G, H, I, K, L, Q, S, T, or Y;   X 4  is Y, C, D, F, H, I, K, L, M, N, Q, R, or S;   X 5  is N, A, D, H, I, K, L, M, P, Q, S, T, V, or W;   X 6  is Y, A, C, D, E, F, G, L, P, R, T, V, or W;   X 7  is S, A, C, F, I, L, N, P, Q, R, T, V, W, or Y;   X 8  is V, A, E, H, I, K, L, M, P, Q, R, W, or Y;   X 9  is V, A, C, D, E, F, G, H, K, L, N, Q, T, or W;   X 10  is G, A, E, F, H, I, K, L, N, P, Q, R, S, V, or Y;   X 11  is G, A, C, F, I, K, L, M, N, Q, R, S, T, V, W, or Y;   X 12  is V, A, D, E, H, K, M, N, S, or W;   X 13  is A, C, D, G, H, L, P, R, S, V, Y, or L;   X 14  is L, A, D, F, G, H, M, N, P, R, S, T, W, or Y; and   X 15  is P, D, F, H, I, K, M, T, or W.       

     In an embodiment, the peptide can have a sequence of EEQGAIVTVKGGLRI (SEQ ID NO: 3). In an embodiment, the peptide can have a sequence of ETPGWIVTVKGGLRI (SEQ ID NO: 4). 
     In an embodiment, the peptide has more than 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% sequence identity to one or more of the peptides stated above. One or more of the peptides stated above can be in the form of a pharmaceutical composition. 
     In some embodiments, the present disclosure relates to a method of treating an allergy comprising administering an effective amount of a pharmaceutical composition comprising any one of the peptides described herein to a subject, e.g., a human subject in need thereof. Such pharmaceutical composition can further comprise a pharmaceutically acceptable excipient, e.g., fillers, diluents, disintegrants, binders and lubricants. In an embodiment, the pharmaceutical composition further comprises a pharmaceutically acceptable additive. In an embodiment, the additive is selected from the group consisting of flavoring agents, coloring agents, taste-masking agents, pH-adjusting agents, buffering agents, preservatives, stabilizing agents, anti-oxidants, wetting agents, humidity-adjusting agents, surface-active agents, suspending agents and absorption enhancing agents. 
     In some embodiments, the present disclosure relates to a method for identifying an epitope for treating an allergy comprising the steps:
         a). predicting potential epitopes based proteomes of microbiome and that of an allergen;   b). filtering the potential epitopes obtained in step a) to result in a list of epitopes;   c). reengineering the list of epitopes obtained in step b) to result in the new epitope.       

     In an embodiment, a filter criterion is applied in step b). In an embodiment, the filter criterion comprises the potential epitopes having more than 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% sequence identity to any one or all of the peptide described herein. In an embodiment, the filter criterion comprises removing sequences that are not directly associated with bacteria. In an embodiment, the filter criterion comprises the molecular docking over human leukocyte antigen (HLA) class II. 
     In some embodiments, the present disclosure relates to a method for producing a peptide inhibitor for the treatment of Crohn&#39;s disease, the method comprising:
         a). identifying one or more binding regions of an HLA class II protein and/or hemagglutinin to I2 superantigen;   b). determining a first peptide sequence corresponding to the one or more binding regions; and   c). producing a peptide inhibitor having a second peptide sequence that is a mutation of the first peptide sequence, wherein the second peptide sequence has a stronger binding affinity to the I2 superantigen than the first peptide sequence.       

     In an embodiment, the mutation is a single amino acid mutation of the first peptide sequence. 
     In an embodiment, the first peptide sequence comprises QGALANIAVDKA (SEQ ID NO: 5). In an embodiment, the first peptide sequence comprises KQNTLK (SEQ ID NO: 6). 
     In some embodiments, the present disclosure relates to a pharmaceutically acceptable compound having a chemical structure selected from the group consisting of: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
     and pharmaceutically acceptable salts thereof. 
     In some embodiments, the present disclosure relates to a method of treating Crohn&#39;s disease comprising administering an effective amount of a pharmaceutical composition comprising any one or more of the compound described herein to a subject in need thereof. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates a specific example of a general view of the workflow employed to identify “de novo” epitopes from allergen proteins associated to a particular condition. 
         FIG. 2  illustrates a specific example of a complementary workflow, including alternative filtering options, employed to identify “de novo” epitopes from allergen proteins associated to a particular condition. 
         FIG. 3  illustrates a specific example of a complementary workflow, to describe a general process of epitopes prediction methods from virulence factors. 
         FIG. 4  illustrates a specific example of a general view of a workflow employed to identify “de novo” epitopes from allergen proteins associated with peanut allergy. 
         FIG. 5  illustrates the workflow of identifying the association between the host metabolism and major depressive disorder. 
         FIG. 6  illustrates the workflow of identifying the association between the taxonomic groups &amp; functions and mental health conditions. 
         FIG. 7  illustrate SI2-MHC complex three dimensional structure. 
         FIG. 8  illustrate the docking of de novo molecule “mol-6” with I2 receptor. 
     
    
    
     DETAILED DESCRIPTION OF THE DISCLOSURE 
     Definition 
     The articles “a” and “an” as used herein and in the appended claims are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article unless the context clearly indicates otherwise. By way of example, “an element” means one element or more than one element. 
     Embodiments of methods and/or systems can use, include, and/or be associated with bacteria and/or microorganisms strains, bacterial-derived products, proteins and/or epitopes belonging to bacteria, archaea and/or other suitable taxa, such as matching those found in food allergen proteomes. In an embodiment, bacteria-derived epitopes are used to trigger an immune response (e.g., as common vaccines do, etc.), by mimicking the response enabled by the an immune reaction and/or food allergen exposure, and/or decrease the immune reaction caused by the food allergen, virulence factors and/or similar agents. Such approaches (and/or other approaches described herein) can be used in developing, performing, generating, and/or can be otherwise associated with a detection method and/or for preventive vaccines, immunotherapy methods and/or other treatments. In an embodiment, the bacterial-derived products, up to and including the bacterium itself, are used to trigger an immune response, as common vaccines do, by mimicking the response enabled by an allergen and/or a virulence factors derived infection. 
     In examples, the epitope-based approach towards a vaccine development can be a preventive approach for diseases that affect the immune system, such as allergies, autoimmune and/or infectious diseases. In specific examples, any suitable vectors can be used including vaccines, suitable delivery methods such as DNA vectors that code the peptide (e.g., epitope), uses of nanoparticles, polymer-based methods, etc. 
     Virulence factors related with pathogenicity agents, describe an immune response from B or T cells. Under the same idea of food allergy, epitopes from virulence factors can be applied to detection and treatment. 
     In examples, T-cell epitopes-based immunotherapy can lack common disadvantages, providing desensitization avoiding secondary effects, because those epitopes are too short to induce cross-linking to allergen-specific lgE on basophils or mast cells, like CPE can do. In examples, approaches described herein can be based on experimental results that demonstrated that tolerance against a complete allergen can be induced using small allergen-derived peptides, which are recognized by allergen specific T cells. In specific examples, cocktails of defined epitopes or chimeric protein arrangements including the target epitopes can elicit convenient humoral and/or cellular immune responses. 
     Identification of potential T-cell epitopes in the food allergens is essential for development of peptide-based immunotherapy. 
     In examples, in-silica MHC class 11 “de novo” binding prediction of epitopes can represent a significant advantage to guide the screening in in-vivo assays (e.g., thereby reducing expenses; etc.). 
     In embodiments, we developed the following workflow to predict de novo epitopes against one or more food allergies, such as based in pathogen/allergen agent and/or based in bacterial species and/or suitable microorganism taxa, which could potentially be microbiota species present in mouth, gut, vaginal, skin, genitals, nose, and/or any suitable body sites (e.g., healthy sites; unhealthy sites; etc.) in relation to the microbiome. 
     A strategy to identify T-cell epitopes can include first (and/or at any suitable time and frequency) predicting HLA binding peptides by in-silica methods (and/or other suitable approaches). In specific examples, short length peptides (8-20 amino acids), are predicted with the support of methods that include neural networks (ANN), support vector machine (SVM), matrix based (MB) algorithms, and/or their combination, and/or any suitable artificial intelligence approach and/or analytical technique, including any one or more supervised learning (e.g., using logistic regression, using back propagation neural networks, using random forests, decision trees, etc.), unsupervised learning (e.g., using an Apriori algorithm, using K-means clustering), semi-supervised learning, a deep learning algorithm, (e.g., neural networks, a restricted Boltzmann machine, a deep belief network method, a convolutional neural network method, a recurrent neural network method, stacked auto-encoder method, etc.), reinforcement learning (.e.g., using a Q-learning algorithm, using temporal difference learning), regression algorithm (e.g., ordinary least squares, logistic regression, stepwise regression, multivariate adaptive regression splines, locally estimated scatterplot smoothing, etc.),an instance- based method (e.g., k-nearest neighbor, learning vector quantization, self-organization map, etc.), a regularization method (e.g., ridge regression least absolute shrinkage and selection operator, elastic net, etc.), a decision tree learning method (e.g., classification and regression tree, iterative dichotomiser 3, C4.5, chi-squared automatic interaction detection, decision stump, random forest, multivariate adaptive regression splines, gradient boosting machines, etc.), a Bayesian method (e.g., naive Bayes, averaged one-dependence estimators, Bayesian belief network, etc.), a kernel method (e.g., a support vector machine, a radial basis function, a linear discriminant analysis, etc.), a clustering method (e.g. , k-means clustering, expectation maximization, etc.), an associated rule learning algorithm (e.g., an Aprioiri algorithm, and Eclat algorithm, etc.), an artificial neural network method (e.g., a Perceptron method, a back-propagation method, a Hopfield network method, a self-organizing map method, a learning vector quantization method, etc.), an ensemble method (e.g., boosting, bootstrapped aggregation, AdaBoost, stacked generalization, gradient boosting machine method, random forest method, etc.). Additionally or alternatively, any suitable portions of embodiments of methods and/or systems can include, apply employ, perform, use, be based on, and/or otherwise be associated with artificial intelligence approaches and/or analytical techniques described herein. 
     Embodiments can leverage approaches described above and/or herein to predict peptides which can bind to human leukocyte antigen (HLA) class II, that correspond to the human version of the major histocompatibility complex (MHC). HLA complex can present those peptide antigens as epitopes. 
     In embodiments, then (and/or at any suitable time and frequency) the process workflow (e.g., portions of embodiments of a method, etc.) can include at least one or more of: First (and/or at any suitable time and frequency), embodiments can include identifying the microbiota which is present in the healthy (e.g., healthy samples; healthy subjects; etc.) that can be related with the one or more diseases (e.g., microorganism-related condition(s)). At the same time (and/or at any suitable time and frequency), embodiments can include identifying food allergens, proteins or agents. 
     Then (and/or at any suitable time and frequency), embodiments can include associating the allergens with some microbiota through the amino acid and/or genomic sequences. At the same time (and/or at any suitable time and frequency), embodiments can include obtaining a preliminary group of de novo epitopes, such as obtained through epitope prediction methods. In specific examples, the preliminary group of de novo epitopes are filtered, where repetitive sequences of epitopes are removed, such as based on analyzing the proteomes of the microbiome. In specific examples, with those filtered epitopes, a new database(s) can be made. 
     In specific examples, each epitope from the database(s) is correlated with proteome sequences obtained from an inversely-correlated organism proteome database, such as through local pairwise alignment tools (and/or other suitable tools and/or approaches) in order to find “de novo” predicted epitopes in those proteomes. In specific examples, what can be considered as “common epitopes” can be based on the predicted epitopes satisfying the following criteria:
         1. Alignments having more than 60% identity and 90% similarity*.   2. Alignments having 90% identity and more than 8 similar amino acids*. Where “match” is the local similarity of an amino acid position in a pairwise alignment.       

     However, any suitable criteria (e.g., any suitable percent identity, percent matches, number of matches, any suitable percent similarity such as 50% similarity, etc.) can be used. 
     In variations, the common epitopes can be grouped, by agent, identity and/or MHC allele best affinity. However, a decrease of affinity can also considered, depending of the application of the epitope, considering that decreasing affinity, can involve a low sensitization against the allergen, or a better immune response. 
     In embodiments, to classify “common epitopes” according their affinity to the receptor, the database(s) can be tested using filtered de novo epitopes against a protein receptor class 11 structure, using molecular docking simulations, but any suitable simulations and/or processes can additionally or alternatively be performed. 
     In the next stage (and/or at any suitable time and frequency), in a variation to improve the affinity of epitopes for the MHC receptor, it is also possible to subject the best epitopes to a reengineering, which means that every (and/or any suitable number and type of) amino acid can be mutated in-silica, such as by other 22 proteinogenic amino acids (e.g., Alanine, Arginine, Asparagine, Aspartic acid, Cysteine, Glutamic acid, Glutamine, Glycine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine, Valine, Selenocysteine, and Pyrrolysine). In examples, those new epitopes obtained by reengineering can be tested by docking and/or other suitable techniques, and then classified according their energy of binding to the receptor, such as where in this way, it is possible to obtain new epitopes with a better affinity to the receptor. 
     In specific examples, a de-nova list of epitopes are then obtained which are final candidates to be used as preventive, treatment and/or therapeutics and/or diagnostics for one or more diseases (e.g., microorganism-related conditions, autoimmune conditions, etc.). 
     Accordingly in specific examples, a general view of the workflow employed to identify “de novo” epitopes from proteins associated to food allergy, and then search them in proteins from organisms (and/or other suitable approaches described herein; etc.), can be described in  FIG. 1 . 
     Additionally or alternatively, other in-silica methods used as filtering methods associated with protein(s), as detection of secreted proteins, virulence factors, domain identification, statistical filtering, taxonomy filtering, and/or other suitable aspects can be used, such as in  FIG. 2 . 
     Additionally or alternatively, epitopes prediction can be applied from virulence factors (similarly as allergen) to describe potential vaccine candidates, to diagnostic, treatment or any similar therapeutics application which can be used as the scheme shown in  FIG. 3 . 
     Embodiments can include the use of predicted epitopes from any strains of bacteria and/or archaea species and/or reengineered ones, and/or other suitable microorganisms, in different products for the diagnostics, treatment and/or prevention and/or suitable conditions described herein, such as based on approaches described herein. 
     Embodiments can include therapeutic compositions including one or more epitopes described herein, such as epitopes derived from microorganisms described herein and/or other suitable microorganisms, such as for use in diagnostics, therapeutics, and/or other suitable applications, such as in relation to one or more conditions (e.g. Asthma, Bronchitis, Cancer, Graves disease, Hashimoto&#39;s thyroiditis, Hypothyroidism, Lupus, Lyme Disease, Migraine, Multiple Sclerosis, Osteoarthritis, Rheumatoid Arthritis, Sinusitis, Strep throat, Celiac disease, Crohn&#39;s disease, Irritable Bowel Syndrome, Ulcerative Colitis, Yeast infection, Acne, Eczema, Psoriasis, Rosacea, Dental decay, Ectodermal dysplasia, Gingivitis, Periodontal disease, Sjogren&#39;s syndrome, Cold/cough, Diarrhea, Dizziness, Fever, Headache, Insomnia, Migraine, Muscle aches, Rash or other where virus, bacteria or some external agent is related with) described herein, such as based on approaches described herein. Additionally or alternatively, embodiments (e.g., of the method, of diagnostics, of therapeutic compositions, etc.) can include, be for, be performed for, apply, correspond to, be diagnostic of (e.g., for diagnosing, etc.), be therapeutic of (e.g., therapeutic composition including epitopes therapeutic of, etc.), and/or otherwise be associated with one or more conditions, including any one or more of: diseases, symptoms, causes (e.g., triggers, etc.), disorders, associated risk (e.g., propensity scores, etc.), associated severity, behaviors (e.g., caffeine consumption, habits, diets, etc.), and/or any other suitable aspects associated with conditions. Conditions can include one or more disease-related conditions, which can include any one or more of: gastrointestinal-related conditions (e.g., irritable bowel syndrome, inflammatory bowel disease, ulcerative colitis, celiac disease, Crohn&#39;s disease, bloating, hemorrhoidal disease, constipation, reflux, bloody stool, diarrhea, etc.); allergy-related conditions (e.g., allergies and/or intolerance associated with wheat, gluten, dairy, soy, peanut, shellfish, tree nut, egg, etc.); skin- related conditions (e.g., acne, dermatomyositis, eczema, rosacea, dry skin, psoriasis, dandruff, photosensitivity, etc.); locomotor-related conditions (e.g., gout, rheumatoid arthritis, osteoarthritis, reactive arthritis, multiple sclerosis, etc.); autoimmune-related conditions (e.g., Sprue, AIDS, Sjogren&#39;s, Lupus, etc.), endocrine-related conditions (e.g., Hashimoto&#39;s thyroiditis, metabolic disease, etc.), communication-related conditions, sleep-related conditions, metabolic-related conditions, weight-related conditions, pain-related conditions, genetic-related conditions, chronic disease, and/or any other suitable type of disease-related conditions. Additionally or alternatively, microorganism-related conditions can include one or more human behavior conditions which can include any one or more of: caffeine consumption, alcohol consumption, other food item consumption, dietary supplement consumption, probiotic-related behaviors (e.g., consumption, avoidance, etc.), other dietary behaviors, habitué behaviors (e.g., smoking; exercise conditions such as low, moderate, and/or extreme exercise conditions; etc.), menopause, other biological processes, social behavior, other behaviors, and/or any other suitable human behavior conditions. Conditions can be associated with any suitable phenotypes (e.g., phenotypes measurable for a human, animal, plant, fungi body, etc.). 
     Embodiments can include a method for diagnostics and/or therapeutic compositions using “de novo” predicted epitopes and/or reengineered ones, such as derived from suitable microorganism for the treatment and/or prevention of suitable conditions described herein, such as based on approaches described herein. 
     Embodiments can include a method (e.g., a workflow) to identify “de novo” epitopes and/or reengineered ones from proteins belonging to one or more pathogens (e.g., described herein; other suitable microorganisms), and/or searching them in inversely- associated bacteria, such as to propose them as new epitope-based vaccines and/or suitable therapeutic compositions, intended to trigger an immune response, and/or for diagnostics, therapeutics, and/or prevention of any one or more conditions described herein, such as based on approaches described herein. 
     Embodiments can include a method (e.g., a workflow) to identify “de novo” virulence factors and/or epitopes and/or reengineered ones, belonging to one or more pathogens (e.g., described herein; other suitable microorganisms), propose them as new epitope- based vaccines, adjuvants and/or suitable therapeutic compositions, intended to trigger an immune response, and/or for diagnostics, therapeutics, and/or prevention of any one or more conditions described herein, such as based on approaches described herein. 
     Embodiments can include a method for identifying epitopes from non-pathogenic microorganisms (e.g., any suitable type of microorganisms, virus, bacteria, archaea, etc.), such as based off of epitopes derived from pathogenic microorganisms or agents that produce an immunological response; such as finding non-pathogenic microorganism epitopes that are similar, reengineered, and/or analogous to pathogenic microorganism epitopes; such as for facilitating improved safety in relation to epitope usage in diagnostics and/or therapeutics; such as based on using approaches described herein. 
     Embodiments can include one or more therapeutic compositions including one or more epitopes determined based on approaches described herein. 
     Embodiments can include the use of predicted epitopes from allergens and/or reengineered ones, and/or other suitable microorganisms, in different products for the diagnostics, treatment and/or prevention of allergy and/or suitable conditions described herein, such as based on approaches described herein. 
     Embodiments can include therapeutic compositions including one or more epitopes described herein, such as epitopes derived from microorganisms described herein and/or other suitable microorganisms, such as for use in diagnostics, therapeutics, and/or other suitable applications, such as in relation to one or more conditions (e.g., cancer, warts, etc.) described herein, such as based on approaches described herein. 
     Embodiments can include a method for diagnostics and/or therapeutic compositions using “de novo” predicted epitopes and/or reengineered ones, such as derived from microorganisms described herein and/or other suitable microorganism for the treatment and/or prevention of allergy and/or suitable conditions described herein, such as based on approaches described herein. 
     Embodiments can include a method (e.g., a workflow) to identify “de novo” epitopes and/or reengineered ones from proteins belonging to one or more pathogens (e.g., described herein; other suitable microorganisms), and/or searching them in inversely-associated bacteria, such as to propose them as new epitope-based vaccines and/or suitable therapeutic compositions, intended to trigger an immune response, and/or for diagnostics, therapeutics, and/or prevention of any one or more conditions described herein, such as based on approaches described herein. 
     Embodiments can include a method for identifying epitopes from non-pathogenic microorganisms (e.g., any suitable type of microorganisms, virus, bacteria, archaea, etc.), such as based off of epitopes derived from pathogenic microorganisms, such as finding non-pathogenic microorganism epitopes that are similar, reengineered, and/or analogous to pathogenic microorganism epitopes, such as for facilitating improved safety in relation to epitope usage in diagnostics and/or therapeutics, such as based on using approaches described herein. 
     Embodiments can include one or more therapeutic compositions including one or more epitopes determined based on approaches described herein. 
     Embodiments can include a method (e.g., workflow, etc.) to predict T-cell epitopes “de novo” from known allergens, and/or then identify them in mentioned microorganisms, particularly applied to peanut allergy. Here, we used the evidence obtained in a previous submission (U.S. App. No. 62/434,917), which included at least disclosure of high and low abundance of several microorganisms in individuals with peanuts allergy. However, any suitable criteria of association between individuals and microbiome components for peanut allergy can be used. 
     Embodiments can function to include, perform, and/or be associated with in-silica MHC class II “de novo” binding prediction of epitopes, which can represent a significant advantage (e.g., reduced expenses, etc.) over in-vivo assays. 
       Clostridia -containing microbiota can confer food allergy-protective capacity to germ-free mice. Embodiments can include determining, using, and/or otherwise being associated with proteins from  Clostridia  and/or other microorganisms present in individuals (e.g., any suitable microorganism taxa, etc.) who do not have peanuts allergy may have epitopes in common with peanuts allergen proteins, which could explain the protective effect of  Clostridia.    
     Peanut allergens can share important part of their sequences with other vegetal species, or those results of dietary habits, which can be potentially allergenic. Embodiments can include determining, using, and/or otherwise being associated with vegetable species that describe suitable similarity with peanut allergy, and might be a cause of allergy. 
     In specific examples, some of the bacterial proteins where epitopes in common with allergens are found, including nitronate monooxygenase and pyruvate phosphate dikinase, which are proteins related with short-chain fatty acids metabolism. In specific examples, those proteins showed matches with Arah 14 and Arah 15, proteins from allergens involved in oil and fatty acids metabolism. 
     In an embodiment, the development of de novo (new) epitope can be followed the following steps. 
     Obtaining Allergen Proteins (Performable at any Time and Frequency) 
     In examples, the method can include determining one or more allergen proteins, such as from academic sources (e.g., literature, etc.), databases, and/or other suitable sources. Allergen proteins from  Arachis hypogaea  (peanut) described to date have been classified under 17 types. However, only 15 have been described in literature and validated (Arah 1-15, Table 1). In this example, Arah sequences from Uniprot database were clustered (with 90% of identity) to obtain only one representative sequence for each Arah type; however clustering and/or other suitable approach can be performed using any suitable identity threshold and/or any suitable condition to obtain one or more representative sequences. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Examples of Peanuts allergen proteins (e.g., evaluated using approaches 
               
               
                 described herein; etc.) 
               
            
           
           
               
               
            
               
                 Protein 
                 Type* 
               
               
                   
               
               
                 Ara h 1 
                 Cupin (Vicillin-type, 7S globulin) 
               
               
                 Ara h 2 
                 Conglutin (2S albumin) 
               
               
                 Ara h 3 
                 Cupin (Legumin-type, 11S globulin, Glycinin) 
               
               
                 Ara h 4 
                 renamed to Ara h 3.02, number not available for future 
               
               
                   
                 submissions 
               
               
                 Ara h 5 
                 Profilin 
               
               
                 Ara h 6 
                 Conglutin (2S albumin) 
               
               
                 Ara h 7 
                 Conglutin (2S albumin) 
               
               
                 Ara h 8 
                 Pathogenesis-related protein, PR-10, Bet v 1 family  
               
               
                   
                 member 
               
               
                 Ara h 9 
                 Nonspecific lipid-transfer protein type 1 
               
               
                 Ara h 10 
                 16 kDa oleosin 
               
               
                 Ara h 11 
                 14 kDa oleosin 
               
               
                 Ara h 12 
                 Defensin 
               
               
                 Ara h 13 
                 Defensin 
               
               
                 Ara h 14 
                 Oleosin 
               
               
                 Ara h 15 
                 Oleosin 
               
               
                 Agglutinin 
                 Not - 
               
               
                   
                 arah type, but recognized as Allergen (galactose binding) 
               
               
                   
               
            
           
         
       
     
     In embodiments, the method can include the following workflow to predict de nova epitopes from peanut allergens, and/or then, identify if those epitopes are present in gut microbiome (and/or present in any suitable microbiome associated with any body site including one or more of gut site, mouth site, nose site, genital site, skin site, etc.) from healthy and/or unhealthy patients (e.g., with or without peanut allergy). 
     In examples, the method can include identifying one or more T cell epitopes, such as through first (and/or at any suitable time and frequency, etc.) predicting one or more de nova HLA binding peptides by in-silica methods. As an example, we first (and/or at any suitable time and frequency) considered Ara-h allergens described in the Table I and processed under an Epitopes Prediction Pipeline, and obtaining lists of 15 mers predicted peptides (but any suitable peptides of any suitable size can be predicted). In examples, through this pipeline (and/or suitable approaches described herein, etc.), peptides can be predicted that bind human leukocyte antigen (HLA) class II, corresponding to the human counterpart of the maj or histocompatibility complex (MHC). Considering that HLA class  11  susceptibility varies typically between 9 and 20 amino acids, that range could be potentially included, such instead 15 mers length, but any suitable ranges and sizes can be used. Thus, HLA complex is able to present those peptide antigens as epitopes. The HLA alleles which have been described to provoke a higher incidence of peanut allergy were considered: 
     HLA-DRB1*O1 :01, HLA-DRB1*03:01,HLA-DRB1*04:01, HLA-DRB1*04:05, HLA-DRB1*08:02, HLA-DRB1*09:01, HLA-DRB1*11:01, HLA-DRB1*12:01, HLA-DRB1*13:02, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01, HLA-DRB5*01:01, HLA-DQA1*05:01/DQB1*02:01, HLA-DQA1*05:01/DQB1*03:01, HLA-DQA1*03:01/DQB1*03:02, HLA-DQA1*04:01/DQB1*04:02, HLA-DQA1*01:01/DQB1*05:01, HLA-DPA1*02:01/DPB1*01:01, HLA-DPA1*01:03/DPB1*02:01, HLA-DPA1*01/DPB1*04:01, HLA-DPA1*03:01/DPB1*04:02, HLA-DPA1*02:01/DPB1*05:01, HLA-DPA1*02:01/DPB 1*14:01, HLA-DQA1*02:01/DQB1*06:02, HLA-DQA1*01:02/DQB1*06:02, HLA-DRB1*07:01. 
     However, any suitable criteria to do a particular group or selection of HLA alleles can be used. 
     In examples, the list of unique epitopes was obtained after discard duplicated epitopes. Then (and/or at any suitable time and frequency), to find those epitopes in proteomes from associated bacteria, each epitope was aligned against each protein sequence, using local pairwise alignment tools (but any suitable alignment tools and/or suitable tools can be used). In examples, a “common epitope” between epitopes from peanuts allergens and from bacteria proteomes are those that meet the following criteria:
         a. Alignments having more than 70% identity and 90% similarity*.   b. Alignments having 90% identity and more than 11 similar amino acids*.
 
Where “match” is the local similarity of an amino acid position in a pairwise alignment.
       

     However, any suitable criteria (e.g., any suitable percent identity, percent matches, number of matches, any suitable percent similarity such as 60% identity, 8 similar amino acids, etc.) can be used. 
     In examples, then (and/or at any suitable time and frequency), the method can include determining a first screening of “common epitopes” according their affinity to the receptor, such as by testing our database of filtered de nova epitopes against a protein receptor class ii structure, using molecular docking simulations, but any suitable simulations and/or processes can additionally or alternatively be performed. In specific examples, the epitopes can be reengineered to improve (and/or eventually decrease) the immune response against MHC class II receptors, such as mutating by the 20 proteinogenic amino acids (Alanine, Arginine, Asparagine, Aspartic acid, Cysteine, Glutamic acid, Glutamine, Glycine, Histidine, isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine, Valine) (and/or suitable amino acids). In examples, the new epitopes obtained by reengineering can be tested by docking and/or other suitable techniques, and/or then classified according to their energy of binding to the receptor (and/or using any suitable criteria). In examples, in this way, it is possible to obtain new epitopes with a better affinity to the receptor. 
     In examples, a general view of the workflow employed to identify “de novo” epitopes from pathogen proteins associated to a particular condition, and then search them in proteomes from associated organisms (and/or other suitable approaches), can be shown in  FIG. 4 . 
     Embodiments can include, use, and/or be associated with, Bacteria present in high abundance in individuals who do not have peanuts allergy contains proteins could elicit protection against that type of allergy, where, those bacteria, such as  F. saccharivorans , might help individuals to do not trigger allergy. Consequently, epitopes found in proteins from those inversely-correlated bacteria can be considered for an allergy diagnostic and/or treatment method, system, and/or therapeutic composition. 
     In embodiments, epitopes from directly associated microorganisms (e.g., whose abundance is high in presence of allergy) can be used as a peanuts allergy diagnostics method. 
     In embodiments, the epitopes identification platform can be used to detect bacterial proteins/bacteria and/or suitable microorganisms that can be related to food allergies. 
     Embodiments can include the integration of “de nova” epitopes or reengineered ones as a part of a new protein and their potential application for the treatment and/or prevention of peanut or any nut allergy. 
     Embodiments can include the use of de-nova predicted T-cell epitopes, and/or reengineered ones, belonging to bacteria that are augmented (directly associated) in individuals with peanut allergy:  FlavonifraGtor plautii, LaGhnospira peGtinosGhiza, Dorea longiGatena, Anaerostipes  sp. 5_1_63FAA,  Blautia  sp.  SerB, Die/ma fastidiosa, Barnesiella intestinihominis, Alistipes  sp. EBA6-25Gl2,  Anaerostipes  sp. 3_2_56FAA,  BaGteroides vulgatus, Eisenbergiella tayi, Kluyvera georgiana, BaGteroides Glarus, AnaerotrunGus Golihominis, PhasGolarGtobaGterium faeGium, Alistipes  sp. RMA 9912,  FlavonifraGtor plautii, OdoribaGter splanGhniGus, BaGteroides fragilis, Bilophila  sp. 4_1_30,  BaGteroides  sp. D22,  AdlerGreutzia equolifaGiens, ErysipelatoGlostridium ramosum, Eggerthella  sp. HGA1,  LaGtonifaGtor longoviformis, GordonibaGter pamelaeae, Blautia  sp. YHC-4,  BaGteroides massiliensis  in different products as a diagnostics and/or treatment method, system, and/or therapeutic composition of peanuts or any related food which contain one or more protein related with peanut allergen. 
     Embodiments can include the use of de-nova predicted T-cell epitopes, and/or reengineered ones, belonging to bacteria that are decreased (inversely associated) in individuals with peanut allergy, and thus including one or more of:  FusiGatenibaGter saGGharivorans, LaGtobaGillus  sp. BL302,  LaGtobaGillus Grispatus, FaeGalibaGterium prausnitzii, Roseburia  sp. 11SE39,  Roseburia inulinivorans, Blautia luti, Alistipes  sp. NML05A004,  Collinsella aerofaGiens, Haemophilus parainfluenzae, Dorea formiGigenerans, BaGteroides thetaiotaomiGron  in different products for treatment and/or prevention of peanuts and/or any nut allergy. 
     Embodiments can include the use of de-nova predicted T-cell epitopes, and/or reengineered ones, as the association of bacteria itself with allergen related with peanut including one or more of:  Ethanoligenens harbinense, AdlerGreutzia equolifaGiens, Alistipes  sp. EBA6-25Gl2,  Alistipes  sp. NML05A004,  Alistipes  sp. RMA 9912,  AnaeroGolumna aminovaleriGa, AnaeroGolumna GellulosilytiGa, AnaeroGolumna jejuensis, AnaeroGolumna xylanovorans, AnaerosalibaGter massiliensis, Anaerostipes  sp. 3_2_56FAA,  Anaerostipes  sp. 5_1_63FAA,  AnaerotrunGus rubiinfantis, BaGteroides Glarus, BaGteroides massiliensis, BaGteroides ovatus, BaGteroides plebeius, BaGteroides  sp. D22,  BaGteroides sterGoris, BaGteroides thetaiotaomiGron, BaGteroides uniformis, Barnesiella intestinihominis, Bifidobacterium adolescentis, Bilophila  sp. 4_1_30,  Blautia caecimuris, Blautia coccoides, Blautia glucerasea, Blautia hansenii, Blautia hominis, Blautia hydrogenotrophica  CAG:147,  Blautia luti, Blautia marasmi, Blautia massiliensis, Blautia obeum, Blautia phocaeensis, Blautia producta, Blautia provencensis, Blautia  sp.,  Blautia  sp. SerB,  Blautia  sp. YHC-4,  Butyrivibrio  cf.  fibrisolvens  EAT6,  Butyrivibrio crossotus  CAG:259,  Butyrivibrio fibrisolvens, Butyrivibrio hungatei, Butyrivibrio proteoclasticus, Butyrivibrio  sp.,  Caproiciproducens galactitolivorans, Clostridia  cluster /Va,  Clostridia  cluster X/Va,  Clostridia  cluster X/Vb,  Clostridium difficile, Clostridium leptum, Collinsella aerofaciens, Coprococcus comes  CAG:19,  Coprococcus eutactus, Coprococcus eutactus  CAG:665,  Cysticercus cellulosi, Die/ma fastidiosa, Dorea formicigenerans, Dorea longicatena, Eggerthella  sp. HGA1,  Eisenbergiella tayi, Eubacterium aggregans, Eubacterium albensis, Eubacterium callanderi, Eubacterium dolichum  CAG:375,  Eubacterium eligens  CAG:72,  Eubacterium  ha/Iii CAG: 12,  Eubacterium pectinii, Eubacterium rectale  CAG:36,  Eubacterium siraeum  CAG:80,  Eubacterium  sp.,  Eubacterium ventriosum, Eubacterium xylanophilum, Faecalibacterium  sp.,  Faecalicatena contorta, Faecalicatena fissicatena, Faecalicatena orotica, Flavonifractor  sp.,  Fusicatenibacter saccharivorans, Gordonibacter pamelaeae, Haemophilus parainfluenzae, Helicobacter pylori, Hungate/la effluvii, Hungate/la hathewayi, Kluyvera georgiana, Lachnoclostridium edouardi, Lachnoclostridium pacaense, Lachnoclostridium phocaeense, Lachnoclostridium  sp.,  Lachnoclostridium urinimassiliense, Lachnospira pectinoschiza, Lactobacillus crispatus, Lactobacillus  sp. BL302,  Odoribacter splanchnicus, Oscilibacter massiliensis, Peptostreptococcus anaerobius  CAG:621,  Peptostreptococcus glycinophilus, Peptostreptococcus  sp.,  Phascolarctobacterium faecium, Prevotella tannerae, Pseudoflavonifractor phocaeensis, Pseudoflavonifractor  sp.,  Roseburia cecicola, Roseburia intestinalis  CAG:13,  Roseburia  sp.,  Roseburia  sp. 11SE39,  Ruminococcus gnavus, Ruminococcus obeum  CAG:39,  Ruminococcus  spp.,  Sporobacter  sp.,  Subdoligranulum variabile, Tissierella carlieri, Urmitella timonensis, [Clostridium] aerotolerans, [Clostridium] aldenense, [Clostridium] algidixylanolyticum, [Clostridium] aminophilum, [Clostridium] amygdalinum, [Clostridium] asparagiforme, [Clostridium] bolteae, [Clostridium] celerecrescens, [Clostridium] citroniae, [Clostridium] clostridioforme, [Clostridium] cocleatum, [Clostridium] fimetarium, [Clostridium] glycyrrhizinilyticum, [Clostridium] herbivorans, [Clostridium] hylemonae, [Clostridium] indolis, [Clostridium] innocuum, [Clostridium] lavalense, [Clostridium] methoxybenzovorans, [Clostridium] polysaccharolyticum, [Clostridium] populeti, [Clostridium] saccharogumia, [Clostridium] saccharolyticum, [Clostridium] scindens, [Clostridium] sphenoides, [Clostridium] symbiosum, [Clostridium] ultunense, [Clostridium] xylanolyticum, [Desulfotomaculum] guttoideum, [Eubacterium] cellulosolvens, [Eubacterium] eligens, [Eubacterium] ha/Iii, [Ruminococcus] gnavus, [Ruminococcus] gnavus  CAG:126, [ Ruminococcus] torques, [Ruminococcus] torques  CAG:61,  cetitomaculum ruminis, Subdoligranulum variabile, Lactonifactor longoviformis, Clostridia  cluster X/Va,  Clostridia  cluster IV. 
     Embodiments can include a workflow to identify “de novo” epitopes or reengineered ones from proteins belonging to a pathogen, and search them in inversely-associated bacteria, to propose them as new epitope-based vaccines intended to trigger an immune response. 
     Embodiments can include, use, and/or otherwise be associated with additional or alternative species related with peanut, inoculated through a similarity by allergens: 
     Arah1, Arah2, Arah3, Arah4:  Anacardium occidentale, Bertholletia excelsa, Cory/us ave/Jana, Fagopyrum esculentum, Glycine max, Jug/ans nigra, Jug/ans regia, Sesamum indicum.    
     Arah5:  Ananas comosus, Apium graveolens, Arabidopsis thaliana, Arachis hypogaea, Betula verrucosa  ( Betula pendula ),  Capsicum annuum, Chenopodium album, Cory/us ave/Jana, Cucumis melo, Cynodon dactylon, Daucus carota, Glycine max, Helianthus annuus, Hevea brasiliensis, Litchi chinensis, Lycopersicon esculentum, Ma/us domestica, Mercurialis annua, Musa acuminata, Olea europea, Parietaria judaica, Phleum pratense, Prunus avium, Prunus persica, Pyrus communis, Triticum aestivum.    
     Arah6, Arah7:  Ambrosia artemisiifolia, Anacardium occidentale, Arachis hypogaea, Bertholletia excelsa, Brassica juncea, Brassica napus, Cory/us ave/Jana, Fagopyrum esculentum, Glycine max, Hevea brasiliensis, Hordeum vulgare, Jug/ans nigra, Jug/ans regia, Lycopersicon esculentum, Ma/us domestica, Oryza sativa, Parietaria judaica, Prunus armeniaca, Prunus avium, Prunus domestica, Prunus persica, Pyrus communis, Ricinus communis, Sesamum indicum, Sinapis alba, Triticum aestivum, Vitis vinifera, Zea mays.    
     Arah8:  A/nus glutinosa, Apium graveolens, Arachis hypogaea, Betula verrucosa  ( Betula pendula ),  Carpinus betulus, Castanea sativa, Cory/us ave/Jana, Daucus carota, Glycine max, Ma/us domestica, Petroselinum crispum, Phaseolus vulgaris, Prunus armeniaca, Prunus avium, Pyrus communis, Taraxacum officinale.    
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Additional or alternative information of each epitope, and which protein of bacteria was found: 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 SEQUENCE_ 
                   
                   
                   
                   
                   
                   
                 DESCRIPTION_ 
                   
                   
               
               
                 EPI- 
                 ID_ 
                   
                 QUERY_ 
                 SUBJECT_ 
                   
                 SIMILI- 
                   
                 SEQUENCE_ID_ 
                 Obtained 
                 Core 
               
               
                 TOPE 
                 PROTEOM 
                 PRQTEOME 
                 ALIGN 
                 ALIGN 
                 IDENTITY 
                 TUDE 
                 ALIGN 
                 PROTEOME 
                 from 
                 (9mer) 
               
               
                   
               
               
                 GTIIG 
                 tr| 
                 Barnesiella_ 
                 TIIGL 
                 TMLGLA 
                 0.714 
                 0.929 
                 9 + 
                 _Uncharacterized_ 
                 Arah14 
                 IGLAI 
               
               
                 LAIAT 
                 K0XJA7| 
                 intestini- 
                 AIAT 
                 MATAPV 
                   
                   
                 14 
                 protien_OS = 
                   
                 ATPV 
               
               
                 PVFTF 
                 K0XJA7_ 
                 hominis 
                 PVFT 
                 FT 
                   
                   
                   
                 Barnesiella_ 
                   
                   
               
               
                   
                 9BACT 
                   
                   
                   
                   
                   
                   
                 intestinihominis_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 YIT_11860_GN = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 HMPREF9448_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 01764_PE = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 4_SV = 1 
                   
                   
               
               
                   
               
               
                 LGTII 
                 tr| 
                 Barnesiella 
                 TIIGL 
                 TMLGLA 
                 0.714 
                 0.929 
                 9 + 
                 _Uncharacterized 
                 Arah14 
                 IGLAI 
               
               
                 GLAIA 
                 K0XJA7| 
                 _intestini- 
                 AIAT 
                 MATAPV 
                   
                   
                 14 
                 _protien_OS = 
                   
                 ATPV 
               
               
                 TPVFT 
                 K0XJA7_ 
                 hominis 
                 PVFT 
                 FT 
                   
                   
                   
                 Barnesiella_ 
                   
                   
               
               
                   
                 9BACT 
                   
                   
                   
                   
                   
                   
                 intestinihominis_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 YIT_11860_GN = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 HMPREF9448_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 01764_PE = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 4_SV = 1 
                   
                   
               
               
                   
               
               
                   
               
               
                 TIIGL 
                 tr| 
                 Barnesiella 
                 TIIGL 
                 TMLGLA 
                 0.714 
                 0.929 
                 9 + 
                 _Uncharacterized_ 
                 Arah14 
                 IGLAI 
               
               
                 AIATP 
                 K0XJA7| 
                 _intestini 
                 AIAT 
                 MATAPV 
                   
                   
                 14 
                 protien_OS = 
                   
                 ATPV 
               
               
                 VFTFF 
                 K0XJA7_ 
                 hominis 
                 PVFT 
                 FT 
                   
                   
                   
                 Barnesiella_ 
                   
                   
               
               
                   
                 9BACT 
                   
                   
                   
                   
                   
                   
                 intestinihominis_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 YIT_11860_GN = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 HMPREF9448_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 01764_PE = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 4_SV = 1 
                   
                   
               
               
                   
               
               
                 AGVaL 
                 tr| 
                 collinsella_ 
                 AGVAL 
                 ASVALA 
                 0.714 
                 0.929 
                 14 
                 _Nitronate_ 
                 Arah3 
                 LSRLV 
               
               
                 SRLVL 
                 A0A173 
                 aerofaciens_ 
                 SRLVL 
                 RLVARR 
                   
                   
                   
                 monooxygenese_ 
                   
                 LRRN 
               
               
                 RRNAL 
                 WNP0| 
                 UP000095468 
                 RRNA 
                 GA 
                   
                   
                   
                 OS = 
                   
                   
               
               
                   
                 A0A173 
                   
                   
                   
                   
                   
                   
                 collinsella_ 
                   
                   
               
               
                   
                 WNP0_ 
                   
                   
                   
                   
                   
                   
                 aerofaciens_GN = 
                   
                   
               
               
                   
                 9ACTN 
                   
                   
                   
                   
                   
                   
                 ERS852381_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 00160_PE = 4_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 SV = 1 
                   
                   
               
               
                   
               
               
                 CAGVA 
                 tr| 
                 collinsella_ 
                 AGVAL 
                 ASVALA 
                 0.714 
                 0.929 
                 14 
                 _Nitronate_ 
                 Arah3 
                 LSRLV 
               
               
                 LSRLV 
                 A0A173 
                 aerofaciens_ 
                 SRLVL 
                 RLVARR 
                   
                   
                   
                 monooxygenese_ 
                   
                 LRRN 
               
               
                 LRRNA 
                 WNP0| 
                 UP000095468 
                 RRNA 
                 GA 
                   
                   
                   
                 OS = 
                   
                   
               
               
                   
                 A0A173 
                   
                   
                   
                   
                   
                   
                 collinsella_ 
                   
                   
               
               
                   
                 WNP0_ 
                   
                   
                   
                   
                   
                   
                 aerofaciens_GN = 
                   
                   
               
               
                   
                 9ACTN 
                   
                   
                   
                   
                   
                   
                 ERS852381_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 00160_PE = 4_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 SV = 1 
                   
                   
               
               
                   
               
               
                 PAAIT 
                 tr| 
                 collinsella_ 
                 ITLAL 
                 ISLALL 
                 0.818 
                 0.909 
                 5 + 
                 _L-aspartate_ 
                 Arah15 
                 ITLAL 
               
               
                 LALAA 
                 A0A17 
                 aerofaciens_ 
                 AaGGF 
                 AAGGF 
                   
                   
                 15 
                 transporter_OS = 
                   
                 AAGG 
               
               
                 GGFLF 
                 3X9L7| 
                 UP000095468 
                   
                   
                   
                   
                   
                 Collinsella_ 
                   
                   
               
               
                   
                 AQA173 
                   
                   
                   
                   
                   
                   
                 aerofaciens_GN = 
                   
                   
               
               
                   
                 X9L7_ 
                   
                   
                   
                   
                   
                   
                 yveA_PE = 4_ 
                   
                   
               
               
                   
                 9ACTN 
                   
                   
                   
                   
                   
                   
                 SV = 1 
                   
                   
               
               
                   
               
               
                 GVALS 
                 tr| 
                 collinsella_ 
                 VALSR 
                 VALARL 
                 0.75 
                 0.917 
                 12 
                 _Nitronate_ 
                 Arah3 
                 LVLR 
               
               
                 RLVLR 
                 A0A17 
                 aerofaciens_ 
                 lvlrrHA 
                 VARRGA 
                   
                   
                   
                 monooxygenese_OS = 
                   
                 RNALR 
               
               
                 RNALR 
                 3WNP0| 
                 UP000095468 
                   
                   
                   
                   
                   
                 collinsella_ 
                   
                   
               
               
                   
                 AOA173W 
                   
                   
                   
                   
                   
                   
                 aerofaciens_GN = 
                   
                   
               
               
                   
                 NP0_ 
                   
                   
                   
                   
                   
                   
                 ERS852381_ 
                   
                   
               
               
                   
                 9ACTN 
                   
                   
                   
                   
                   
                   
                 00160_PE = 4_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 SV = 1 
                   
                   
               
               
                   
               
               
                 VALSR 
                 tr| 
                 collinsella_ 
                 VALSR 
                 VALARL 
                 0.75 
                 0.917 
                 12 
                 _Nitronate_ 
                 Arah3 
                 IVLR 
               
               
                 LVLRS 
                 A0A17 
                 aerofaciens_ 
                 lvlrrN 
                 VARRGA 
                   
                   
                   
                 monooxygenese_ 
                   
                 RNALR 
               
               
                 NALRR 
                 3WNP0| 
                 UP000095468 
                 A 
                   
                   
                   
                   
                 OS = 
                   
                   
               
               
                   
                 AOA173 
                   
                   
                   
                   
                   
                   
                 collinsella_ 
                   
                   
               
               
                   
                 WNP0_ 
                   
                   
                   
                   
                   
                   
                 aerofaciens_GN = 
                   
                   
               
               
                   
                 9ACTN 
                   
                   
                   
                   
                   
                   
                 ERS852381_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 00160_PE = 4_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 SV = 1 
                   
                   
               
               
                   
               
               
                 LLGIL 
                 tr| 
                 Eggerthella_ 
                 LLGIL 
                 LLGLLV 
                 0.75 
                 0.917 
                 12 
                 _Putative_ 
                 Arah1 
                 ILVLA 
               
               
                 VLASV 
                 F0HJV5| 
                 sp._HGA1 
                 VLASV 
                 IALVSA 
                   
                   
                   
                 membrane 
                   
                 SVSA 
               
               
                 SATHA 
                 F0HJV5_ 
                   
                 SA 
                   
                   
                   
                   
                 protien_OS = 
                   
                   
               
               
                   
                 9ACTN 
                   
                   
                   
                   
                   
                   
                 Eggerthella_sp._ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 HAGA1_GN = HMPR 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 EF9404_3564_PE = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 4_SV = 1 
                   
                   
               
               
                   
               
               
                 GNVAS 
                 tr| 
                 Erysipelato- 
                 GNVAS 
                 GEVADF 
                 0.75 
                 0.917 
                 6 − 
                 _DegT/DnrJ/EryC1/ 
                 Agglutinin_ 
                 FLTS 
               
               
                 FLTSF 
                 B0N353| 
                 clostridium_ 
                 FLTSF 
                 TSFSF 
                   
                   
                 15 
                 strS_ 
                 LECG_ 
                 FSFEM 
               
               
                 SFEMK 
                 B0N353_ 
                 ramosum 
                 SF 
                   
                   
                   
                   
                 aminotransferase_ 
                   
                   
               
               
                   
                 9FIRM 
                   
                   
                   
                   
                   
                   
                 family_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 protien_OS = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 Erysipelato 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 clostridium_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 ramosum_DSM_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 1403_GN = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 CLORAM_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 00871_PE = 3_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 _SV = 1 
                   
                   
               
               
                   
               
               
                 TGNV 
                 tr| 
                 Erysipelato- 
                 GNV 
                 GEVA 
                 0.75 
                 0.917 
                 6 − 
                 _DegT/DnrJ/EryC1/ 
                 Agglutinin_ 
                 FLTS 
               
               
                 ASFL 
                 B0N353| 
                 clostridium_ 
                 ASFL 
                 DFTSF 
                   
                   
                 15 
                 strS_ 
                 LECG_ 
                 FSFEM 
               
               
                 TSFS 
                 B0N353_ 
                 ramosum 
                 TSFS 
                 SF 
                   
                   
                   
                 aminotransferase_ 
                   
                   
               
               
                 FEM 
                 9FIRM 
                   
                 F 
                   
                   
                   
                   
                 family_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 protien_OS = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 Erysipelato 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 clostridium_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 ramosum_DSM_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 1403_GN = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 CLORAM_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 00871_PE = 3_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 _SV = 1 
                   
                   
               
               
                   
               
               
                 ANYA 
                 tr| 
                 falvonii_ 
                 A 
                 AYGY 
                 0.75 
                 0.917 
                 12 
                 _Uncharacterized_ 
                 Arah8 
                 YNYSV 
               
               
                 YNYS 
                 G9YM06| 
                 factor_ 
                 YNYS 
                 AVVL 
                   
                   
                   
                 protien_OS = 
                   
                 VGGV 
               
               
                 VVGG 
                 353| 
                 plautii 
                 VVGG 
                 VVAL 
                   
                   
                   
                 falvoniifactor_ 
                   
                   
               
               
                 VAL 
                 G9YM06_ 
                   
                 VAL 
                   
                   
                   
                   
                 plautii_ 
                   
                   
               
               
                   
                 9FIRM 
                   
                   
                   
                   
                   
                   
                 ATCC_29863_GN = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 HMPREF0372_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 00521_PE = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 4_SV = 1 
                   
                   
               
               
                   
               
               
                 NYAY 
                 tr| 
                 falvonii_ 
                 A 
                 AYGY 
                 0.75 
                 0.917 
                 12 
                 _Uncharacterized_ 
                 Arah8 
                 YNYSV 
               
               
                 NYSV 
                 G9YM06| 
                 factor_ 
                 YNYS 
                 AYYL 
                   
                   
                   
                 protien_OS = 
                   
                 VGGV 
               
               
                 VGGV 
                 353| 
                 plautii 
                 VVGG 
                 GVAL 
                   
                   
                   
                 falvoniifactor_ 
                   
                   
               
               
                 ALP 
                 G9YM06_ 
                   
                 VAL 
                   
                   
                   
                   
                 plautii_ 
                   
                   
               
               
                   
                 9FIRM 
                   
                   
                   
                   
                   
                   
                 ATCC_29863_GN = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 HMPREF0372_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 00521_PE = 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 4_SV = 1 
                   
                   
               
               
                   
               
               
                 EEQG 
                 tr| 
                 Fusicateni 
                 QG 
                 QG 
                 0.727 
                 0.909 
                 2 − 
                 _Pyruvate_ 
                 Arah3 
                 IVTVT 
               
               
                 AIVT 
                 A0A17 
                 bacter_ 
                 AIVT 
                 ILT 
                   
                   
                 18 
                 phosphate_ 
                   
                 GGLR 
               
               
                 VRGG 
                 4PZ33| 
                 sacchari- 
                 VRGG 
                 VRG 
                   
                   
                   
                 dikinase_ 
                   
                   
               
               
                 LRI 
                 A0A174 
                 vorans 
                 L 
                 GM 
                   
                   
                   
                 OS = Fusicateni 
                   
                   
               
               
                   
                 PZ33_ 
                   
                   
                   
                   
                   
                   
                 bacter_ 
                   
                   
               
               
                   
                 9FIRM 
                   
                   
                   
                   
                   
                   
                 saccharivorans_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 GN = ppdX_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 PE = 4_SV = 1 
                   
                   
               
               
                   
               
               
                 EQGA 
                 tr| 
                 Fusicateni 
                 QGA 
                 QG 
                 0.727 
                 0.909 
                 2 − 
                 _Pyruvate_ 
                 Arah3 
                 IVTVT 
               
               
                 IVTV 
                 A0A17 
                 bacter_ 
                 IVTV 
                 ILT 
                   
                   
                 18 
                 phosphate_ 
                   
                 GGLR 
               
               
                 RGGL 
                 4PZ33| 
                 sacchari- 
                 RGGL 
                 VRG 
                   
                   
                   
                 dikinase_ 
                   
                   
               
               
                 RIL 
                 A0A174 
                 vorans 
                   
                 GM 
                   
                   
                   
                 OS = Fusicateni 
                   
                   
               
               
                   
                 PZ33_ 
                   
                   
                   
                   
                   
                   
                 bacter_ 
                   
                   
               
               
                   
                 9FIRM 
                   
                   
                   
                   
                   
                   
                 saccharivorans_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 GN = ppdX_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 PE = 4_SV = 1 
                   
                   
               
               
                   
               
               
                 QGAI 
                 tr| 
                 Fusicateni 
                 QGA 
                 QG 
                 0.727 
                 0.909 
                   
                 _Pyruvate_ 
                 Arah3 
                 IVTVT 
               
               
                 VTVR 
                 A0A17 
                 bacter_ 
                 IVTV 
                 ILT 
                   
                   
                   
                 phosphate_ 
                   
                 GGLR 
               
               
                 GGLR 
                 4PZ33| 
                 sacchari- 
                 RGGL 
                 VRG 
                   
                   
                   
                 dikinase_ 
                   
                   
               
               
                 ILS 
                 A0A174 
                 vorans 
                   
                 GM 
                   
                   
                   
                 OS = Fusicateni 
                   
                   
               
               
                   
                 PZ33_ 
                   
                   
                   
                   
                   
                   
                 bacter_ 
                   
                   
               
               
                   
                 9FIRM 
                   
                   
                   
                   
                   
                   
                 saccharivorans_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 GN = ppdX_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 PE = 4_SV = 1 
                   
                   
               
               
                   
               
               
                 FSGG 
                 tr| 
                 pseudo 
                 FSGG 
                 FSGGC 
                 0.8 
                 0.9 
                 5 + 
                 _Uncharacterized_ 
                 Arah15 
                 GVAAI 
               
               
                 CGVA 
                 A6NR8| 
                 flavoni- 
                 CGVA 
                 IGVSA 
                   
                   
                 14 
                 protien_OS = 
                   
                 AALS 
               
               
                 AIAA 
                 A6NR88_ 
                 fractor_ 
                 A 
                   
                   
                   
                   
                 flavonifractor_ 
                   
                   
               
               
                 LSW 
                 9FIRM 
                 capillosus 
                   
                   
                   
                   
                   
                 capillosus_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 ATCC_29799_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 GN = BACCAP_00713_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 PE = 4_SV = 1 
                   
                   
               
               
                   
               
               
                 AGGF 
                 tr| 
                 pseudo 
                 GFL 
                 GLLFS 
                 0.769 
                 0.923 
                 8 + 
                 _Uncharacterized_ 
                 Arah15 
                 FSGGC 
               
               
                 LFSG 
                 A6NR8| 
                 flavoni- 
                 FSGG 
                 GGGCG 
                   
                   
                 14 
                 protien_OS = 
                   
                 GVAA 
               
               
                 GCGV 
                 A6NR88_ 
                 fractor_ 
                 CGVA 
                 VSA 
                   
                   
                   
                 flavonifractor_ 
                   
                   
               
               
                 AAI 
                 9FIRM 
                 capillosus 
                 A 
                   
                   
                   
                   
                 capillosus_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 ATCC_29799_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 GN = BACCAP_00713_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 PE = 4_SV = 1 
                   
                   
               
               
                   
               
               
                 GFLF 
                 tr| 
                 pseudo 
                 GFLF 
                 GLLFS 
                 0.769 
                 0.923 
                 8 + 
                 _Uncharacterized_ 
                 Arah15 
                 GCGV 
               
               
                 SGGC 
                 A6NR8| 
                 flavoni- 
                 SGGC 
                 GGGCG 
                   
                   
                 14 
                 protien_OS = 
                   
                 AAIAA 
               
               
                 GVAA 
                 A6NR88_ 
                 fractor_ 
                 GVAA 
                 VSA 
                   
                   
                   
                 flavonifractor_ 
                   
                   
               
               
                 IAA 
                 9FIRM 
                 capillosus 
                   
                   
                   
                   
                   
                 capillosus_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 ATCC_29799_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 GN = BACCAP_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 00713_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 PE = 4_SV = 1 
                   
                   
               
               
                   
               
               
                 GGFL 
                 tr| 
                 pseudo 
                 GFL 
                 GLLFS 
                 0.769 
                 0.923 
                 8 + 
                 _Uncharacterized_ 
                 Arah15 
                 DGGC 
               
               
                 FSGG 
                 A6NR8| 
                 flavoni- 
                 FSGG 
                 GGGCG 
                   
                   
                 14 
                 protien_OS = 
                   
                 GVAAI 
               
               
                 CGVA 
                 A6NR88_ 
                 fractor_ 
                 CGVA 
                 VSA 
                   
                   
                   
                 flavonifractor_ 
                   
                   
               
               
                 AIA 
                 9FIRM 
                 capillosus 
                 A 
                   
                   
                   
                   
                 capillosus_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 ATCC_29799_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 GN = BACCAP_00713_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 PE = 4_SV = 1 
                   
                   
               
               
                   
               
               
                 LFSG 
                 tr| 
                 pseudo 
                 LFSGG 
                 LFSGG 
                 0.818 
                 0.909 
                 6 + 
                 _Uncharacterized_ 
                 Arah15 
                 CGVA 
               
               
                 GCGV 
                 A6NR8 
                 flavoni- 
                 C 
                 CIGYS 
                   
                   
                 14 
                 protien_OS = 
                   
                 AIAAL 
               
               
                 AAIA 
                 8|A6NR6 
                 fractor_ 
                 GVAA 
                 A 
                   
                   
                   
                 flavonifractor_ 
                   
                   
               
               
                 ALS 
                 8_9FIRM 
                 capillosus 
                   
                   
                   
                   
                   
                 capillosus_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 ATCC_29799_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 GN = BACCAP_00713_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 PE = 4_SV = 1 
                   
                   
               
               
                   
               
               
                 FLFS 
                 tr| 
                 pseudo 
                 FLFSG 
                 LLFSG 
                 0.75 
                 0.917 
                 7 + 
                 _Uncharacterized_ 
                 Arah15 
                 FSSGC 
               
               
                 GGC 
                 A6NR8 
                 flavoni- 
                 GC 
                 GCIGV 
                   
                   
                 14 
                 protien_OS = 
                   
                 GVaA 
               
               
                 GVAA 
                 8|A6NR6 
                 fractor_ 
                 GVAA 
                 SA 
                   
                   
                   
                 flavonifractor_ 
                   
                   
               
               
                 IAAL 
                 8_9FIRM 
                 capillosus 
                   
                   
                   
                   
                   
                 capillosus_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 ATCC_29799_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 GN = BACCAP_00713_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 PE = 4_SV = 1 
                   
                   
               
               
                   
               
               
                 LLGIL 
                 tr|A6NV 
                 pseudo 
                 LLGILV 
                 LLGLL 
                 0,75 
                 0.917 
                 12 
                 _Uncharacterized_ 
                 Arah1 
                 ILV 
               
               
                 VLAS 
                 M1|A6NV 
                 flavoni- 
                 LASVS 
                 VLVIV 
                   
                   
                   
                 protien_OS = 
                   
                 LAS 
               
               
                 VSAT 
                 M1_ 
                 fractor_ 
                 A 
                 SA 
                   
                   
                   
                 flavonifractor_ 
                   
                 VSA 
               
               
                 HA 
                 9FIRM 
                 capillosus 
                   
                   
                   
                   
                   
                 capillosus_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 ATCC_29799_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 GN = BACCAP_00713_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 PE = 4_SV = 1 
                   
                   
               
               
                   
               
               
                 VFLT 
                 tr|A6NP 
                 pseudo 
                 VFLTF 
                 VILTF 
                 0.75 
                 0.917 
                 8 + 
                 _Uncharacterized_ 
                 Agglutinin_ 
                 FLLLA 
               
               
                 FFLLL 
                 V3|A6NP 
                 flavoni- 
                 FLL 
                 FFLSL 
                   
                   
                 12 
                 protien_OS = 
                 LECG_ 
                 ASSK 
               
               
                 AASS 
                 V3_ 
                 fractor_ 
                 LAA 
                 AA 
                   
                   
                   
                 flavonifractor_ 
                   
                   
               
               
                 KK 
                 9FIRM 
                 capillosus 
                   
                   
                   
                   
                   
                 capillosus_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 ATCC_29799_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 GN = BACCAP_00713_ 
                   
                   
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                 PE = 4_SV = 1 
               
               
                   
               
            
           
         
       
     
     Embodiments of the method can, however, include any other suitable blocks or steps configured to facilitate reception of biological samples from subjects, processing of biological samples from subjects, analyzing data derived from biological samples, and generating models that can be used to provide customized diagnostics and/or probiotic- based therapeutics according to specific microbiome compositions and/or functional features of subjects. 
     Embodiments of the method and/or system can include every combination and permutation of the various system components and the various method processes, including any variants (e.g., embodiments, variations, examples, specific examples, figures, etc.), where portions of embodiments of the method and/or processes described herein can be performed asynchronously (e.g., sequentially), concurrently (e.g., in parallel), or in any other suitable order by and/or using one or more instances, elements, components of, and/or other aspects of the system and/or other entities described herein. 
     Any of the variants described herein (e.g., embodiments, variations, examples, specific examples, figures, etc.) and/or any portion of the variants described herein can be additionally or alternatively combined, aggregated, excluded, used, performed serially, performed in parallel, and/or otherwise applied. 
     Portions of embodiments of the method and/or system can be embodied and/or implemented at least in part as a machine configured to receive a computer-readable medium storing computer-readable instructions. The instructions can be executed by computer-executable components that can be integrated with the system. The computer-readable medium can be stored on any suitable computer-readable media such as RAMs, ROMs, flash memory, EEPROMs, optical devices (CD or DVD), hard drives, floppy drives, or any suitable device. The computer-executable component can be a general or application specific processor, but any suitable dedicated hardware or hardware/firmware combination device can alternatively or additionally execute the instructions. 
     As a person skilled in the art will recognize from the previous detailed description and from the figures and claims, modifications and changes can be made to embodiments of the method, system, and/or variants without departing from the scope defined in the claims. 
     In another aspect, this disclosure relates to a discovery of correlations between neurological disorders and taxonomic groups and functions from the microbiome. In an embodiment, the correlation is between the taxonomic groups &amp; functions and mental health conditions, including anxiety, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, chronic fatigue syndrome, depression, and stroke. In an embodiment, the discovery comprises four steps: 1. Transformation; 2. Removal of technical variation; 3, Dimension reduction; and 4. Modelling. A workflow of the procedure is illustrated in  FIG. 6 . 
     In an embodiment, the correlation is between the taxonomic groups &amp; functions and anxiety. It was found that anxiety is associated with alterations in more than 20 gut microbiome metabolic functions, for example, carbohydrate metabolism. Gut bacteria dysregulation of carbohydrate metabolism pathway may produce a higher energy demand and consequently, less activity levels as a symptom of anxiety. The test results are shown below based on 5947 gut samples of anxiety patients and 1265 gut samples of healthy patients. 
     
       
         
           
               
               
            
               
                   
               
               
                 Positively Associated Bacteria      
                 Negatively Associated Bacteria      
               
            
           
           
               
               
               
               
            
               
                 Species 
                 Odds ratio 
                 Species 
                 Odds ratio 
               
               
                   
               
               
                   Negativicoccus _ succinicivorans   
                 15.237 
                   Anaerotruncus _ colihominis   
                 0.012 
               
               
                   Flavonifractor _ plautii   
                 11.686 
                   Murdochiella _ asaccharolytica   
                 0.014 
               
               
                   Propionimicrobium _ lymphophilum   
                  4.054 
                   Varibaculum _ cambriense   
                 0.018 
               
               
                   Blautia _ hydrogenotrophica   
                  2.729 
                   Lactobacillus _ gasseri   
                 0.021 
               
               
                   Actinomyces _ europaeus   
                  2.510 
                   Corynebacterium _ pyruviciproducens   
                 0.034 
               
               
                   Corynebacterium _ glaucum   
                  2.254 
                   Anaerococcus _ senegaiensis   
                 0.040 
               
               
                   Peptoniphilus _ duerdenii   
                  2.085 
                   Anaerococcus _ octavius   
                 0.057 
               
               
                   Corynebacterium _ imitans   
                  2.057 
                   Parabacteroides _ gordonii   
                 0.105 
               
               
                   Lactobacillus _ crispatus   
                  1.764 
                   Eggerthella _ lenta   
                 0.143 
               
               
                   Finegoldia _ magna   
                  1.726 
                   Corynebacterium _ appendicis   
                 0.177 
               
               
                   Blautia _ faecis   
                  1.375 
                   Corynebacterium _ jeikeium   
                 0.243 
               
               
                   Prevoteila _ corporis   
                  1.311 
                   Mathanosphaera _ stadtmanae   
                 0.299 
               
               
                   Bacteroides _ fragilis   
                  1.276 
                   Facklamia _ ignava   
                 0.323 
               
               
                   Atopobium _ vaginae   
                  1.251 
                   Eremococcus _ coleocola   
                 0.394 
               
               
                   Tyzzerelia _ nexilis   
                  1.153 
                   Arthrobacter _ cumminsii   
                 0.500 
               
               
                   Corynebacterium _ aurimucosum   
                  1.140 
                   Brevibacterium _ massiliense   
                 0.530 
               
               
                   
               
            
           
         
       
     
     In an embodiment, the correlation is between the taxonomic groups &amp; functions and depression. The workflow of identifying the host metabolism and major depressive disorder (MDD) is illustrated in  FIG. 5 . It was found that depression is associated with alterations in more than 20 gut microbiome metabolic functions, for example, sphingolipid metabolism. High-fat diet induces depression-like behavior in mice associated with changes in the microbiome that count affect sphingolipid metabolism. The test results are shown below based on 5767 gut samples of depression patients and 1265 gut samples of healthy patients. 
     
       
         
           
               
               
            
               
                   
               
               
                 Positively Associated Bacteria      
                 Negatively Associated Bacteria      
               
            
           
           
               
               
               
               
            
               
                 Species 
                 Odds ratio 
                 Species 
                 Odds ratio 
               
               
                   
               
               
                   Flavonifractor _ plautii   
                 2.9293 
                   Hoidemania _ filiformis   
                 0.0065 
               
               
                   Mitsuokella _ jalatudinii   
                 2.2383 
                   Anaerotruncus _ colihominis   
                 0.0110 
               
               
                   Dielma _ fastidiosa   
                 2.1213 
                   Slackia _ exigua   
                 0.0255 
               
               
                   Parabacteroides _ goldsteinii   
                 2.1029 
                   Pephoniphilus _ obesi   
                 0.0329 
               
               
                   Bacteroides _ nordii   
                 1.5838 
                   Eubacterium _ coprostanoligenes   
                 0.1682 
               
               
                   Phascolarctobacterium _ faecium   
                 1.2091 
                   Facklamia _ hominis   
                 0.1828 
               
               
                   Bacteroides _ fragilis   
                 1.1541 
                   Coprococcus _ catus   
                 0.2689 
               
               
                   Parabacteroides _ distasonis   
                 1.1502 
                   Coprobacilius _ cateniformis   
                 0.3541 
               
               
                   Roseburia _ inulinivorans   
                 1.1418 
                   Anaetostipes _ caccae   
                 0.3674 
               
               
                   Prevoteila _ bivia   
                 1.1414 
                   Eggerthelia _ lenta   
                 0.4838 
               
               
                   Bilophila _ wadsworthia   
                 1.1396 
                   Facklamia _ ignava   
                 0.5208 
               
               
                   Finegoidia _ magna   
                 1.0750 
                   Senegalimassilla _ anaerobia   
                 0.5259 
               
               
                   Erysipelatoclostridium _ ramosum   
                 1.0657 
                   Phascolarctobacterium _ succinatutens   
                 0.7293 
               
               
                   Escherichia _ coli   
                 1.0254 
                   Dorea _ iongicatena   
                 0.7569 
               
               
                   Bacteroides _ dorei   
                 1.0127 
                   Catenibacterium _ mitsuokai   
                 0.8569 
               
               
                   Prevoteila _ corporis   
                 1.0002 
                   Tyzzerelia _ nexilis   
                 0.8837 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Specific example of microorganism taxa associations with depression condition 
               
               
                 and/or suitable neurological-related conditions (e.g., neurological disorders; etc.) 
               
            
           
           
               
               
               
               
               
               
            
               
                 Species 
                 Estimate 
                 Std_Error 
                 z.value 
                 Pr_z —   
                 oddsratio 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   Lactococcus _ raflinolactis   
                 25.92625512 
                 100.6593982 
                 0.2575641776 
                 0.7967432792 
                 181814926552 
               
               
                   Ruminococcus _ gauveaull   
                 24.70085812 
                 15.82844129 
                 1.560536358 
                 0.118633185 
                 53388335304 
               
               
                   Lactonifactor _ longoviformis   
                 12.16837513 
                 7.585223995 
                 1.604220935 
                 0.1086653617 
                 192600.8379 
               
               
                   Catabacter _ hongkongensis   
                 7.243905677 
                 44.48459127 
                 0.1628407831 
                 0.8706437965 
                 1399.549499 
               
               
                   Ezakiella _ peruensis   
                 5.776784609 
                 2.8770511462 
                 2.007883657 
                 0.0446556563 
                 322.71985 
               
               
                   Blautia _ hydrogenotrophica   
                 4.925477517 
                 1.883166366 
                 2.615529677 
                 0.008908917899 
                 137.7551063 
               
               
                   Flavonifractor _ plautii   
                 1.074756929 
                 0.3623787962 
                 2.965838344 
                 0.003018591092 
                 2.929280791 
               
               
                   Mitsuokelia _ jalaludinii   
                 0.8057207134 
                 0.3460498335 
                 2.328337238 
                 0.01989420346 
                 2.238309097 
               
               
                   Dielma _ fastidiosa   
                 0.7520298809 
                 3.31676003 
                 0.2267362951 
                 0.8206288026 
                 2.121301639 
               
               
                   Parabacteroides _ goldsteinii   
                 0.7433142975 
                 0.377155426 
                 1.970843441 
                 0.04874178612 
                 2.102893593 
               
               
                   Bacteroides _ nordii   
                 0.4598274282 
                 0.4161121775 
                 1.105056408 
                 0.2691351477 
                 1.583800642 
               
               
                   Phascolarctobacterium _ faecium   
                 0.1898497981 
                 0.08631944639 
                 2.199386188 
                 0.02785047391 
                 1.20906798 
               
               
                   Bacteroides _ fragilis   
                 0.143319106 
                 0.06989655104 
                 2.050446035 
                 0.04032092479 
                 1.154098022 
               
               
                   Parabacteroides _ distasonis   
                 0.1399064057 
                 0.0644175361 
                 2.171868316 
                 0.0298655969 
                 1.150166145 
               
               
                   Roseburia _ inulinivorans   
                 0.1325807887 
                 0.1334045184 
                 0.9938253236 
                 0.3203079152 
                 1.141771255 
               
               
                   Prevotella _ bivia   
                 0.1322498156 
                 0.2044677207 
                 0.6468004591 
                 0.5177610952 
                 1.141393422 
               
               
                   Bilophila _ wadsworthia   
                 0.1306891544 
                 0.1431310902 
                 0.9130731434 
                 0.3612040741 
                 1.139613482 
               
               
                   Finegoidia _ magna   
                 0.07234557142 
                 0.04412224032 
                 1.639662241 
                 1.1010754141 
                 1.075026778 
               
               
                   Erysipelatoclostridium _ ramosum   
                 0.06365580729 
                 0.7502243897 
                 0.08484902406 
                 0.9323814185 
                 1.065725521 
               
               
                   Escherichia _ coli   
                 0.02509884321 
                 0.03218956316 
                 0.7797199077 
                 0.4355557583 
                 1.025416471 
               
               
                 Bacteroides_ dorei   
                 0.01259406637 
                 0.01293352046 
                 0.9737539296 
                 0.330178733 
                 1.012673706 
               
               
                   Prevotella _ corporis   
                 0.0001784591323 
                 0.07616242943 
                 0.002343138653 
                 0.9981304476 
                 1.000178475 
               
               
                   Ruminococcus _ lastaris   
                 −0.002506467631 
                 0.1852290938 
                 −0.01353171675 
                 0.9892035816 
                 0.9974966709 
               
               
                   Prevotella _ copri   
                 −0.006006660422 
                 0.01006321154 
                 −0.5971135951 
                 0.05504315417 
                 0.9940091368 
               
               
                   Faecalibacterium _ prausnitzii   
                 −0.01555792055 
                 0.01163830363 
                 −1.336785931 
                 0.1812925339 
                 0.9845624787 
               
               
                   Bacteroides _ caccae   
                 −0.02260762112 
                 0.04209459773 
                 −0.5370670428 
                 0.591221305 
                 0.9776460162 
               
               
                   Ruminococcus _ bicirculans   
                 −0.03481920224 
                 0.0450024059 
                 −0.7737186833 
                 0.439097169 
                 0.9657800113 
               
               
                   Staphylococcus _ aureus   
                 −0.05387622358 
                 0.06751085759 
                 −0.7980379084 
                 0.4248484919 
                 0.9475493835 
               
               
                   Akkermansia _ muciniphilia   
                 −0.05939841805 
                 0.03426110215 
                 −1.733698402 
                 0.08297161019 
                 0.9423312526 
               
               
                   Collinselia _ aerofaciens   
                 −0.08065078472 
                 0.05458390385 
                 −1.477556185 
                 0.1395266093 
                 0.9225157918 
               
               
                   Tyzzerelia _ nexilis   
                 −0.1236303025 
                 0.09618060088 
                 −1.259213138 
                 0.2079533574 
                 0.8837064845 
               
               
                   Catenibacterium _ mitsuokai   
                 −0.1544717347 
                 0.1193189705 
                 −1.294611696 
                 0.1954542156 
                 0.8568677114 
               
               
                   Dorea _ longicatena   
                 −0.2785384278 
                 0.09928248079 
                 −2.805514383 
                 0.005023633931 
                 0.7568891816 
               
               
                 
                   Phascolarctobacterium 
                   — 
                 
                 −0.3156557789 
                 0.1542750253 
                 −2.046058838 
                 0.04075058215 
                 0.729310451 
               
               
                 
                   succinatutens 
                 
                   
                   
                   
                   
                   
               
               
                   Senegalimassilia _ anaerobia   
                 −0.6425621752 
                 0.4774957255 
                 −1.345691994 
                 0.1784018693 
                 0.5259431378 
               
               
                   Facklamia _ ignava   
                 −0.6522963828 
                 0.5768918567 
                 −1.130708252 
                 0.258177907 
                 0.5208483352 
               
               
                   Eggerthella _ lenta   
                 −0.7261828301 
                 0.6672543125 
                 −1.08831493 
                 0.2764561019 
                 0.483752034 
               
               
                   Anaerostipes _ caccae   
                 −1.001266482 
                 0.7119086622 
                 −1.406453574 
                 0.1595894814 
                 0.3674139233 
               
               
                   Coprobacillus _ cateniformis   
                 −1.038157432 
                 1.305326731 
                 −0.7953237436 
                 0.4264252054 
                 0.3541065784 
               
               
                   Coprococcus _ catus   
                 −1.313387739 
                 0.3922019079 
                 −3.348754078 
                 0.0008117581281 
                 0.2689075231 
               
               
                   Facklamia _ hominis   
                 −1.699317894 
                 2.844072339 
                 −0.5974946104 
                 0.5501772043 
                 0.182808176 
               
               
                   Eubacterium _ coprostanoligenes   
                 −1.782653987 
                 3.027447456 
                 −0.5888306942 
                 0.5559748533 
                 0.1681911771 
               
               
                   Peptoniphilus _ obesi   
                 −3.412858743 
                 2.83962237 
                 −1.201870634 
                 0.2294136537 
                 0.03294687897 
               
               
                   Slackia _ exigua   
                 −3.668734786 
                 9.101934173 
                 −0.4030719972 
                 0.6868952602 
                 0.02550872354 
               
               
                   Anaerotruncus _ colihominis   
                 −4.510705012 
                 3.990003657 
                 −1.130501473 
                 0.258264978 
                 0.01099070886 
               
               
                   Holdemania _ filiformis   
                 −6.036662008 
                 5.425738426 
                 −0.9282906055 
                 0.3532568459 
                 0.006495393741 
               
               
                   Mucispirillum _ schaedieri   
                 −6217.437082 
                 186413.6539 
                 −0.03335290604 
                 0.9733931643 
                 0 
               
               
                   Dysgonomonas _ gadei   
                 −3902.892997 
                 8127638.917 
                 −0.000480200097 
                 0.9996168558 
                 0 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Specific examples of microorganism taxa associations with anxiety conditions 
               
               
                 and/or suitable neurological-related conditions (e.g., neurological disorders; etc.) 
               
            
           
           
               
               
               
               
               
               
            
               
                 Species 
                 Estimate 
                 Std_Error 
                 z.value 
                 Pr_z —   
                 odds ratio 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                   Corynebacterium _ tuscaniense   
                 28.88700848 
                 33.33390603 
                 0.866595366 
                 0.386163754 
                 3.51E+12 
               
               
                   Lactobacillus _ rhamnosus   
                 21.11387021 
                 10.79718117 
                 1.955498373 
                 0.050524275 
                 1477873708 
               
               
                   Peptoniphilus _ obesi   
                 19.99180686 
                 16.37166267 
                 1.221122574 
                 0.222039614 
                 481206407.3 
               
               
                   Actinomyces _ neuii   
                 19.00186185 
                 10.04658753 
                 1.891374738 
                 0.058574338 
                 178814918.6 
               
               
                   Dielma _ fastidiosa   
                 11.73565119 
                 6.640134109 
                 1.767381652 
                 0.077164334 
                 124947.7829 
               
               
                   Granulicateila _ elegans   
                 9.243940721 
                 23.72739094 
                 0.38958943 
                 0.696840169 
                 10341.71216 
               
               
                   Ezaliella _ peruensis   
                 8.973880479 
                 8.793483021 
                 1.020514904 
                 0.307484325 
                 7894.175426 
               
               
                   Dermabacter _ hominis   
                 6.507886973 
                 23.12230257 
                 0.28145497 
                 0.778361461 
                 670.4083292 
               
               
                   Atopobium _ parvulum   
                 6.411615724 
                 39.99441753 
                 0.0160312767 
                 0.872634703 
                 608.8766631 
               
               
                   Streptococcus _ gordonii   
                 5.614561356 
                 18.19154593 
                 0.308635746 
                 0.757598626 
                 274.392992 
               
               
                   Porphyromonas _ uenonis   
                 5.120162121 
                 3.466553628 
                 1.477018004 
                 0.139670811 
                 167.3625004 
               
               
                   Pseudoclavibacter _ bifida   
                 4.577686684 
                 8.237756448 
                 0.555695803 
                 0.578418826 
                 97.28907331 
               
               
                   Prevotella _ bergensis   
                 4.520988154 
                 7.946104768 
                 0.568956525 
                 0.569385644 
                 91.92639055 
               
               
                   Corynebacterium _ urealyticum   
                 4.186035977 
                 3.47752236 
                 1.203740924 
                 0.22868973  
                 65.76159316 
               
               
                   Lactobacillus _ vaginalis   
                 3.258756064 
                 1.269263358 
                 2.567438857 
                 0.010245286 
                 26.01715334 
               
               
                   Negativicoccus _ succinicivorans   
                 2.723738379 
                 20.62614794 
                 0.132052693 
                 0.894942614 
                 15.23717826 
               
               
                   Flavonifractor _ plautii   
                 2.45841356 
                 0.951815394 
                 2.582868038 
                 0.009798279 
                 11.68625728 
               
               
                   Propionimicrobium _ lymphophilum   
                 1.399646117 
                 1.869289711 
                 0.748758263 
                 0.45400292  
                 4.053765153 
               
               
                   Blautia _ hydrogenotrophica   
                 1.003997618 
                 3.254495371 
                 0.308495636 
                 0.757705221 
                 2.729170231 
               
               
                   Actinomyces _ europaeus   
                 0.920300088 
                 15.85011759 
                 0.058062666 
                 0.953698712 
                 2.51004351 
               
               
                   Corynebacterium _ glaucum   
                 0.812810056 
                 1.046147918 
                 0.776955191 
                 0.437185207 
                 2.254233617 
               
               
                   Peptoniphilus _ duerdenii   
                 0.734753727 
                 3.532209304 
                 0.208015342 
                 0.835216988 
                 2.084968457 
               
               
                   Corynebacterium _ imitans   
                 0.721348024 
                 1.18103059 
                 0.610778443 
                 0.541346267 
                 2.057204504 
               
               
                   Lactobacillus _ crispatus   
                 0.567502033 
                 0.339907225 
                 1.669579199 
                 0.095002649 
                 1.763855491 
               
               
                   Finegoldia _ magna   
                 0.545610605 
                 0.209036 
                 2.610127468 
                 0.009050849 
                 1.725661759 
               
               
                   Blautia _ faecis   
                 0.318525524 
                 0.168852983 
                 1.886407438 
                 0.059240071 
                 1.375098719 
               
               
                   Prevotella _ corporis   
                 0.270961456 
                 0.377306221 
                 0.718147333 
                 0.472666448 
                 1.31122453 
               
               
                   Bacteroides _ fragills   
                 0.243933672 
                 0.074303722 
                 3.282926689 
                 0.001027354 
                 1.276259676 
               
               
                   Atopobium _ vaginae   
                 0.224288419 
                 0.895985969 
                 0.250325816 
                 0.802335393 
                 1.251431904 
               
               
                   Tyzzerella _ nexilis   
                 0.142547638 
                 0.289696869 
                 0.492057918 
                 0.6226784  
                 1.153208016 
               
               
                   Corynebacterium _ aurimucosum   
                 0.131034408 
                 0.493668766 
                 0.265429812 
                 0.790678373 
                 1.140007006 
               
               
                   Bacteroides _ dorei   
                 0.04248077 
                 0.021216196 
                 2.002280182 
                 0.045254606 
                 1.043395991 
               
               
                   Clostridium _ aff   
                 0.038898807 
                 0.351616041 
                 0.110628647 
                 0.91191083  
                 1.039665271 
               
               
                 Facklamia_ languida   
                 0.017621502 
                 1.215040383 
                 0.014502812 
                 0.988428836 
                 1.017777676 
               
               
                   Staphylococcus _ aureus   
                 −0.011099298 
                 0.09793054 
                 −0.113338476 
                 0.909762214 
                 0.988962072 
               
               
                   Helcococcu s_ sueciensis   
                 −0.050673274 
                 2.782691424 
                 −0.018210166 
                 0.985471192 
                 0.950589202 
               
               
                   Holdemania _ filiformis   
                 −0.082775902 
                 11.98352498 
                 −0.006907475 
                 0.994488676 
                 0.920557419 
               
               
                   Bilophiia _ wadsworthia   
                 −0.09606582 
                 0.428295059 
                 −0.224298221 
                 0.822525261 
                 0.908404223 
               
               
                   Bacteroides _ eggerthii   
                 −0.145278783 
                 0.162593845 
                 −0.893507271 
                 0.37158558  
                 0.864781173 
               
               
                   Porphyromonas _ somerae   
                 −0.185986213 
                 3.299746407 
                 −0.05636379 
                 0.955052003 
                 0.830285042 
               
               
                   Bacteroides _ caccae   
                 −0.285970853 
                 0.163276025 
                 −1.75145648 
                 0.079867311 
                 0.751284514 
               
               
                   Actinotignum _ schaalii   
                 −0.542543077 
                 1.079876653 
                 −0.502412082 
                 0.615377682 
                 0.581268161 
               
               
                   Brevibacterium _ massiliense   
                 −0.63525475 
                 1.154210386 
                 −0.550380379 
                 0.582058503 
                 0.529800505 
               
               
                   Arthrobacter _ cumminsii   
                 −0.6932348 
                 1.537019905 
                 −0.451025259 
                 0.651971344 
                 0.499956192 
               
               
                   Eremococcus _ coleocoia   
                 −0.931586328 
                 1.316534356 
                 −0.707605027 
                 0.47919057  
                 0.393928315 
               
               
                   Facklamia _ ignava   
                 −1.12950589 
                 1.96819152 
                 −0.573880071 
                 1.56604896  
                 0.32319291 
               
               
                   Methanosphaera _ stadtmanae   
                 −1.206170934 
                 0.917098773 
                 −1.315202865 
                 0.188441733 
                 0.299341285 
               
               
                   Corynebacterium _ jeikeium   
                 −1.413836488 
                 2.033967949 
                 −0.695112471 
                 0.48698482  
                 0.243208425 
               
               
                   Corynebacterium _ appendicis   
                 −1.732756774 
                 3.850746158 
                 −0.449979485 
                 0.652725233 
                 0.17679635 
               
               
                   Eggerthelia _ lenta   
                 −1.944497166 
                 1.839517495 
                 −1.057069134 
                 0.290480037 
                 0.14305914 
               
               
                   Parabacteroides _ gordonii   
                 −2.253239682 
                 3.946613049 
                 −0.570929973 
                 0.568047112 
                 0.105058317 
               
               
                   Anaerococcus _ octavius   
                 −2.856759275 
                 5.135458001 
                 −0.556281304 
                 0.578018566 
                 0.057454654 
               
               
                   Anaerococcus _ senegaiensis   
                 −3.211024441 
                 2.506104603 
                 −1.281281091 
                 0.200094952 
                 0.040315291 
               
               
                   Corynebacterium _ pyruviciproducens   
                 −3.378515004 
                 5.601837299 
                 −0.603108377 
                 0.546436594 
                 0.034098053 
               
               
                   Lactobacillus _ gasseri   
                 −3.879495278 
                 3.262354057 
                 −1.189170523 
                 0.234372572 
                 0.020661251 
               
               
                   Varibaculum _ cambriense   
                 −4.014206957 
                 1.589684729 
                 −2.525159161 
                 0.01156459  
                 0.018057269 
               
               
                   Murdochiella _ asaccharolytica   
                 −4.278966763 
                 2.26930703 
                 −1.885583003 
                 0.05935117  
                 0.013856972 
               
               
                   Anaerotruncus _ colihominis   
                 −4.400890949 
                 9.97406788 
                 −0.441233306 
                 0.659044103 
                 0.012266406 
               
               
                   Parvimonas _ micra   
                 −4.718913446 
                 13.56532043 
                 −0.347865977 
                 0.727940838 
                 0.008924871 
               
               
                   Oligeila _ urethralis   
                 −14.32726797 
                 2931.657258 
                 −0.004887088 
                 0.996100683 
                 5.99E−07 
               
               
                   Veillonelia _ montpellierensis   
                 −15.25074562 
                 2384.342406 
                 −0.006396206 
                 0.994896601 
                 2.38E−07 
               
               
                   Corynebacterium _ frankenforstense   
                 −15.66630912 
                 1573.347352 
                 −0.009957311 
                 0.992055346 
                 1.57E−07 
               
               
                   Dolosigranulum _ pigrum   
                 −15.7627745 
                 1702.156777 
                 −0.009260472 
                 0.992611318 
                 1.43E−07 
               
               
                   Corynebacterium _ massiliense   
                 −15.96939252 
                 2505.014981 
                 −0.006374969 
                 0.994913545 
                 1.16E−07 
               
               
                   Flavobacterium _ ceti   
                 −16.11439341 
                 1233.22524 
                 −0.01306687 
                 0.989574443 
                 1.00E−07 
               
               
                   Corynebacterium _ negelii   
                 −16.19965849 
                 1956.113512 
                 −0.008281553 
                 0.993392352 
                 9.22E−08 
               
               
                   Bacteroides _ bamesiae   
                 −16.32926677 
                 4019.994832 
                 −0.004062012 
                 0.996758992 
                 8.10E−08 
               
               
                   Actinomyces _ georgiae   
                 −17.21723234 
                 2933.245633 
                 −0.005869687 
                 0.995316695 
                 3.33E−08 
               
               
                   Corynebacterium _ matruchotii   
                 −17.8241343 
                 2276.734553 
                 −0.007828815 
                 0.993753573 
                 1.82E−08 
               
               
                   Meiothermus _ silvanus   
                 −17.89826458 
                 1664.703556 
                 −0.010751623 
                 0.991421612 
                 1.69E−08 
               
               
                   Barnesielia _ intestinihominis   
                 −19.37960413 
                 1353.41733 
                 −0.014319016 
                 0.988575469 
                 3.83E−09 
               
               
                   Solobacterium _ moorei   
                 −19.66994142 
                 25.52075749 
                 −0.770742852 
                 0.440859367 
                 2.87E−09 
               
               
                   Dialister _ pneumosintes   
                 −20.92348439 
                 14.80371047 
                 −1.413394597 
                 0.157539734 
                 8.19E−10 
               
               
                   Capnocytophaga _ gingivalis   
                 −20.96264082 
                 3460.310549 
                 −0.006058023 
                 0.995166427 
                 7.87E−10 
               
               
                   Ignavigranum _ rouffiae   
                 −25.37807617 
                 2096.742142 
                 −0.012103575 
                 0.99034298  
                 9.52E−12 
               
               
                   Gardnerell a_ vaginalis   
                 −27.18677167 
                 27.08955513 
                 −1.003588709 
                 0.315576899 
                 1.56E−12 
               
               
                   Propionibacterium _ avidum   
                 −151.8557409 
                 101.7134754 
                 −1.492975639 
                 0.135443564 
                 1.12E−66 
               
               
                   
               
            
           
         
       
     
     Administration 
     The compounds/peptides of this invention may be administered orally, pulmonary, parenteral (intramuscular, intraperitoneal, intravenous (IV) or subcutaneous injection), inhalation (a fine powder composition), transdermal, intranasal, vaginal, rectal or tongue the administration route, and may be formulated for various routes of administration of the dosage form 
     Embodiments (e.g., of a method, of a system, of a therapeutic composition, etc.) can include one or more (e.g., two, etc.) strategies to inhibit the interaction between Crohn&#39;s disease-associated I2 superantigen and MHC class II, such as for use as a therapy (and/or diagnostics) for CD (e.g., for improving one or more conditions and/or health states associated with CD, etc.). In a specific example, embodiments can include peptide inhibitor and/or small molecules inhibiting the interaction between Crohn&#39;s disease-associated I2 superantigen and MHC class II. 
     Embodiments can function to inhibit this the binding between I2 T-cell superantigen and MHC-II. Embodiments can include designing peptides and/or de novo molecules inhibitors (e.g., for inhibiting the binding between I2 T-cell superantigen and MHC-II. Embodiments can include an in-silico approach involving docking and/or structural biology approaches to design new specific inhibitors against Crohn&#39;s disease. In specific examples, determined (e.g., designed) specific inhibitors can be tested by in vitro experiments, but any suitable experiments and/or validation approaches can additionally or alternatively be used to evaluate specific inhibitors. 
     Embodiments (e.g., therapeutic compositions, formulations etc.) including and/or otherwise associated with the inhibitors can be used as treatment and/or as a palliative against Crohn&#39;s disease and/or Inflammatory bowel disease (IBD), and/or any other condition characterized by an inflammation of the gastrointestinal tract. Conditions can additionally or alternatively include one or more of an abnormal immune system response, chronic inflammation in the digestive tract, abdominal pain, severe diarrhea, fatigue, loss of appetite, fever, cramping, weight loss, ulcers within the intestines, fissures in the lining of the anus, increased risk of colorectal cancer, colorectal cancer, development of chronic health conditions, cardiovascular disease, respiratory disease, cancer, arthritis, kidney diseases, liver diseases, and/or any suitable associated condition. Conditions can include at least one of: symptoms, causes, diseases, disorders, associated risk, associated severity, and/or any other suitable aspects associated with conditions. 
     In an embodiment, the method of producing peptide inhibitors of Crohn&#39; disease-associated I2 superantigen comprises: identifying potential immunogenic peptides from I2 superantigen by identifying the area of interaction with HLA-DR class II using bioinformatics prediction (and/or other suitable approaches), and/or reengineering the peptides corresponding to the HLA-DR class II area of interaction with I2 in-silico, such as to obtain new peptides with higher affinity to I2 and in consequence, inhibit the I2 superantigen/HLA-DR class II interaction. 
     In an embodiment, potential immunogenic peptides belonging to I2 that bind HLA-DRB1*37 and HLA-DRB1*07 alleles were identified using different epitope-prediction softwares. To this, the sequence of I2 superantigen from pfiT gene was obtained from Protein Data Bank database (code: 4M07). Using this method, five peptides of 15 amino acids length comprising the blue region of I2 sequence were identified as potential immunogenic peptides: 
     
       
         
           
               
               
            
               
                   
                 &gt;4M07: 
               
               
                   
                 (SEQ ID NO: 103) 
               
               
                   
                 AIPDBIDICHAINISEQUENCEGPLGSMDEHKALGVMRTMVDS 
               
               
                   
               
               
                   
                 GQLTDPESARGKLLQTAAHLFRNKGFERTTVRDLASAVGIQSG 
               
               
                   
               
               
                   
                 SIFHHFKSKDEILRAVMEENHYNTAMMRASLEEASTVRERVLA 
               
               
                   
               
               
                   
                 LIRCELQSIMGGSGEAMAVLVYEWRSLSAEGQAHVLALRDVYE 
               
               
                   
               
               
                   
                 QIWLQVLGEAKAAGYIRGDVFITRRFLTGALSWTTTWFRAQGS 
               
               
                   
               
               
                   
                 LTLEELAEEALLMVLKSD 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
               
                   
               
               
                 The summary of five peptides: 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Binding area 1 
                 E ETIHYNTAMMRA SL 
                 Peptide 1 
               
               
                   
                   
                 (SEQ ID NO: 104) 
                   
               
               
                   
               
               
                   
                   
                 ME ETIHYNTAMMRA S 
                 Peptide 2 
               
               
                   
                   
                 (SEQ ID NO: 105) 
                   
               
               
                   
               
               
                   
                   
                   ETIHYNTAMMRA SLE 
                 Peptide 3 
               
               
                   
                   
                 (SEQ ID NO: 106) 
                   
               
               
                   
               
               
                   
                   
                 VME ETIHYNTAMMRA   
                 Peptide 4 
               
               
                   
                   
                 (SEQ ID NO: 107) 
                   
               
               
                   
               
               
                   
                 Binding area 2 
                 RGKLLQTAAHLFRNK 
                 Peptide 5 
               
               
                   
                   
                 (SEQ ID NO: 108) 
               
               
                   
               
            
           
         
       
     
     A common region between peptides 1, 2, 3 and 4 is underlined. The common motif among them correspond to the “ETIHYNTAMMRA” (SEQ ID NO: 109) sequence (Binding area 1). The region correspond to Binding area 2 comprising for “RGKLLQTAAHLFRNK” (SEQ ID NO: 108) sequence. Both regions will be used as binding area for docking against HLA-DR. 
     In another embodiment, design of peptide inhibitors can include identifying the corresponding HLA binding region to I2. In a specific example, as shown by competition binding experiments, the predicted I2-binding site to HLA-DR can overlap with the corresponding HLA binding site of mycoplasma arthritidis mitogen (MAM), a phylogenetically and structurally distinct superantigen. In a specific example, based on the crystal structure of the MAM-MHC complex (PDB code: 1R5I), we identified the HLA binding region (from alpha and beta chains) and the hemagglutinin peptide ( FIG. 7 ). In specific examples, the peptides can comprise one or more sequences: QGALANIAVDKA (SEQ ID NO: 110) (from HLA-DR) and/or KQNTLK (SEQ ID NO: 111) (from Hemagglutinin). 
     In specific examples, the peptides corresponding to HLA-DR and Hemagglutinin binding regions to I2 will be reengineered in the following stage. 
     In a specific example, in a first step (and/or performable at any suitable time and frequency in any suitable order), a structural analysis was performed to identify whether the immunogenic peptides of I2 superantigen from  P. fluorescens  are exposed to the solvent and therefore, can interact with the HLA-DR class II receptor. Thus, the solvent-accessible surface area (SASA) was calculated for these 5 peptides (and/or any suitable number of peptides) considering all (and/or any suitable amount of) the protein structure of the superantigen. In a specific example, all the peptides were predicted to be on the surface of the protein. 
     Then (and/or performable at any suitable time and frequency in any suitable order), a control molecular docking was performed to model the interaction between I2 superantigen and the two peptides (and/or suitable number of peptides) corresponding to HLA and Hemagglutinin binding regions: “QGALANIAVDKA” (SEQ ID NO: 110) and “KQNTLK” (SEQ ID NO: 111). However, any suitable modeling and/or approaches can be performed to evaluate the interactions between any suitable peptides and/or regions. In a specific example, the peptides were considered flexible for docking, in order to evaluate all the possible conformations. In a specific example, the docking binding energy were −5.9 and −5.7 kcal/mol respectively. 
     In a specific example, considering this, we designed new inhibitors against I2 superantigen to treat or palliate Crohn&#39;s disease based on reengineering of the two “QGALANIAVDKA” (SEQ ID NO: 110) and “KQNTLK” (SEQ ID NO: 111) peptides (but any suitable types of peptides can be reengineered, and/or selected for reengineering based on any suitable criteria). In this way, the new peptides can have better affinity to I2 than for those two peptides and can prevent the binding of I2 to HLA-DR. The modifications can include mutating each position of peptides for the 19 amino acids remaining (and/or any suitable number of amino acids). In a specific example, subsequently, docking between modified peptides and I2 superantigen was performed; and finally, a number of contacts analysis between the I2 receptor and the inhibitory modified peptides was performed to determine the main amino acids involved with the interaction. In a specific example, a distance of 5 angstrom was considered for the analysis (but any suitable distance can be used). According to the above specific examples, the results can be shown in Table 6 and Table 7: 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Specific examples of results of single mutations 
               
               
                 on “QGALANIAVDKA” (SEQ ID NO: 110) 
               
               
                 inhibitory peptide. The first column corresponds 
               
               
                 to amino acid mutation and the of the number 
               
               
                 position in the peptide. The second column 
               
               
                 corresponds to the sequence reengineered peptide. 
               
               
                 The third column is the complex docking affinity 
               
               
                 energy expressed in kcal/mol. The fourth 
               
               
                 column corresponds to the total number of 
               
               
                 amino acids of 12 that interact with the 
               
               
                 inhibitory peptide. 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 Complex 
                 Total 12 
               
               
                   
                   
                 affinity 
                 contacts 
               
               
                 Mutation 
                 Peptide 
                 energy 
                 number 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 Al2F 
                 QGALANIAVDKF 
                 −7 
                 28 
               
               
                   
                 (SEQ ID NO: 112) 
                   
                   
               
               
                   
               
               
                 G2W 
                 PWALANIAVDKA 
                 −6.9 
                 25 
               
               
                   
                 (SEQ ID NO: 113) 
                   
                   
               
               
                   
               
               
                 L4W 
                 PWALANIAVDKA 
                 −6.9 
                 29 
               
               
                   
                 (SEQ ID NO: 114) 
                   
                   
               
               
                   
               
               
                 V9W 
                 QGALANIAVVDKA 
                 −6.9 
                 27 
               
               
                   
                 (SEQ ID NO: 115) 
                   
                   
               
               
                   
               
               
                 K11T 
                 QGALANIAVDTA 
                 −6.8 
                 27 
               
               
                   
                 (SEQ ID NO: 116) 
                   
                   
               
               
                   
               
               
                 V9P 
                 QGALANIAPDKA 
                 −6.7 
                 28 
               
               
                   
                 (SEQ ID NO: 117) 
                   
                   
               
               
                   
               
               
                 I7R 
                 QGALANRAVDKA 
                 −6.6 
                 28 
               
               
                   
                 (SEQ ID NO: 118) 
                   
                   
               
               
                   
               
               
                 N6L 
                 OGALALIAVDKA 
                 −6.6 
                 31 
               
               
                   
                 (SEQ ID NO: 119) 
                   
                   
               
               
                   
               
               
                 A85 
                 QGALANIAGDKA 
                 −6.6 
                 26 
               
               
                   
                 (SEQ ID NO: 120) 
                   
                   
               
               
                   
               
               
                 V9R 
                 QGALANIARDKA 
                 −6.5 
                 27 
               
               
                   
                 (SEQ ID NO: 121) 
                   
                   
               
               
                   
               
               
                 WOE 
                 GALANIAVEKA 
                 −6.5 
                 29 
               
               
                   
                 (SEQ ID NO: 122) 
                   
                   
               
               
                   
               
               
                 17G 
                 QGALANGAVDKA 
                 −6.5 
                 26 
               
               
                   
                 (SEQ ID NO: 123) 
                   
                   
               
               
                   
               
               
                 Al2H 
                 C/GALANIAVDKH 
                 −6.5 
                 27 
               
               
                   
                 (SEQ ID NO: 124) 
                   
                   
               
               
                   
               
               
                 ASL 
                 QGALLNIAVDKA 
                 −6.5 
                 26 
               
               
                   
                 (SEQ ID NO: 125) 
                   
                   
               
               
                   
               
               
                 01F 
                 FGALANIAVDKA 
                 −6.5 
                 28 
               
               
                   
                 (SEQ ID NO: 126) 
                   
                   
               
               
                   
               
               
                 K11E 
                 OGALANIAVDEA 
                 −6.4 
                 27 
               
               
                   
                 (SEQ ID NO: 127) 
                   
                   
               
               
                   
               
               
                 V9G 
                 QGALANIAGDKA 
                 −6.4 
                 27 
               
               
                   
                 (SEQ ID NO: 128) 
                   
                   
               
               
                   
               
               
                 K11H 
                 OGALANIAVDHA 
                 −6.4 
                 28 
               
               
                   
                 (SEQ ID NO: 129) 
                   
                   
               
               
                   
               
               
                 A8H 
                 OGALANIHVDKA 
                 −6.4 
                 27 
               
               
                   
                 (SEQ ID NO: 130) 
                   
                   
               
               
                   
               
               
                 A31 
                 QGILANIAVDKA 
                 −6.4 
                 27 
               
               
                   
                 (SEQ ID NO: 131) 
                   
                   
               
               
                   
               
               
                 G2P 
                 QPALANIAVDKA 
                 −6.4 
                 25 
               
               
                   
                 (SEQ ID NO: 132) 
                   
                   
               
               
                   
               
               
                 L4Y 
                 QGAYANIAVDKA 
                 −6.4 
                 26 
               
               
                   
                 (SEQ ID NO: 133) 
                   
                   
               
               
                   
               
               
                 G2F 
                 QFALANIAVDKA 
                 −6.3 
                 25 
               
               
                   
                 (SEQ ID NO: 134) 
                   
                   
               
               
                   
               
               
                 AST 
                 QGALTNIAVDKA 
                 −6.3 
                 26 
               
               
                   
                 (SEQ ID NO: 135) 
                   
                   
               
               
                   
               
               
                 D1OW 
                 QGALANIAVVVKA 
                 −6.3 
                 26 
               
               
                   
                 (SEQ ID NO: 136) 
                   
                   
               
               
                   
               
               
                 A3W 
                 QGWLANIAVDKA 
                 −6.3 
                 27 
               
               
                   
                 (SEQ ID NO: 137) 
                   
                   
               
               
                   
               
               
                 L4T 
                 QGATANIAVDKA 
                 −6.2 
                 27 
               
               
                   
                 (SEQ ID NO: 138) 
                   
                   
               
               
                   
               
               
                 17W 
                 QGALANWAVDKA 
                 −6.2 
                 25 
               
               
                   
                 (SEQ ID NO: 139) 
                   
                   
               
               
                   
               
               
                 G2Y 
                 QYALANIAVDKA 
                 −6.2 
                 25 
               
               
                   
                 (SEQ ID NO: 140) 
                   
                   
               
               
                   
               
               
                 A8Y 
                 OGALANIYVDKA 
                 −6.2 
                 26 
               
               
                   
                 (SEQ ID NO: 141) 
                   
                   
               
               
                   
               
               
                 17D 
                 QGALANDAVDKA 
                 −6.1 
                 29 
               
               
                   
                 (SEQ ID NO: 142) 
                   
                   
               
               
                   
               
               
                 I7C 
                 QGALANCAVDKA 
                 −6.1 
                 25 
               
               
                   
                 (SEQ ID NO: 143) 
                   
                   
               
               
                   
               
               
                 V9E 
                 QGALANIAEDKA 
                 −6.1 
                 29 
               
               
                   
                 (SEQ ID NO: 144) 
                   
                   
               
               
                   
               
               
                 Al2N 
                 QGALANIAVDKQ 
                 −6 
                 30 
               
               
                   
                 (SEQ ID NO: 145) 
                   
                   
               
               
                   
               
               
                 A8N 
                 OGALANIOVDKA 
                 −6 
                 28 
               
               
                   
                 (SEQ ID NO: 146) 
                   
                   
               
               
                   
               
               
                 N6K 
                 QGALAKIAVDKA 
                 −6 
                 27 
               
               
                   
                 (SEQ ID NO: 147) 
                   
                   
               
               
                   
               
               
                 K11V 
                 QGALAKIAVDKA 
                 −6 
                 25 
               
               
                   
                 (SEQ ID NO: 148) 
                   
                   
               
               
                   
               
               
                 A8V 
                 QGALANIVVDKA 
                 −6 
                 28 
               
               
                   
                 (SEQ ID NO: 149) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Specific examples of results of single mutations 
               
               
                 on “KQNTLK” (SEQ ID NO: 111) inhibitory peptide. 
               
               
                 The first column corresponds to amino acid 
               
               
                 mutation and the position in the peptide. The 
               
               
                 second column corresponds to peptide sequence. 
               
               
                 The third column includes the docking complex 
               
               
                 affinity energy expressed in kcal/mol. The 
               
               
                 fourth column corresponds to the total number 
               
               
                 of amino acids of 12 that interact with the 
               
               
                 inhibitory peptide. 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 Complex 
                 Total 12 
               
               
                   
                   
                 affinity 
                 contacts 
               
               
                 Mutation 
                 Peptide 
                 energy 
                 number 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 K1W 
                 WQNTLK (SEQ ID NO: 150) 
                 −6.6 
                 23 
               
               
                   
               
               
                 K6W 
                 KQNTLW (SEQ ID NO: 151) 
                 −6.4 
                 22 
               
               
                   
               
               
                 K6Y 
                 KQNTLY (SEQ ID NO: 152) 
                 −6.4 
                 25 
               
               
                   
               
               
                 K6P 
                 KQNTLP (SEQ ID NO: 153) 
                 −6.2 
                 23 
               
               
                   
               
               
                 K3P 
                 KQPTLK (SEQ ID NO: 154) 
                 −6.1 
                 25 
               
               
                   
               
               
                 K1V 
                 VQNTLK (SEQ ID NO: 155) 
                 −6.1 
                 22 
               
               
                   
               
               
                 Q2N 
                 KNNTLK (SEQ ID NO: 156) 
                 −6 
                 22 
               
               
                   
               
               
                 N3I 
                 KQITLK (SEQ ID NO: 157) 
                 −6 
                 21 
               
               
                   
               
               
                 LDS 
                 KQNTDK (SEQ ID NO: 158) 
                 −6 
                 22 
               
               
                   
               
               
                 Q2T 
                 KTNTLK (SEQ ID NO: 159) 
                 −6 
                 23 
               
               
                   
               
               
                 K6R 
                 KQNTLR (SEQ ID NO: 160) 
                 −5.9 
                 22 
               
               
                   
               
               
                 K1S 
                 SQNTLK (SEQ ID NO: 161) 
                 −5.9 
                 22 
               
               
                   
               
               
                 Q2P 
                 KPNTLK (SEQ ID NO: 162) 
                 −5.8 
                 22 
               
               
                   
               
               
                 N3D 
                 KQDTLK (SEQ ID NO: 163) 
                 −5.8 
                 23 
               
               
                   
               
               
                 T4V 
                 KQNVLK (SEQ ID NO: 164) 
                 −5.8 
                 22 
               
               
                   
               
               
                 K1L 
                 LQNTLK (SEQ ID NO: 165) 
                 −5.8 
                 21 
               
               
                   
               
            
           
         
       
     
     In an embodiment, the peptide inhibitor described herein has the following characteristics: an affinity energy of less than −5.7 kcal/mol for the case of the “KQNTLK” (SEQ ID NO: 111) peptide and less than −5.9 kcal/mol for the “QGALANIAVDKA” (SEQ ID NO: 110) peptide and/or high number of total contacts. 
     In an embodiment, the present disclosure relates to a therapeutic composition comprising a peptide comprising a sequence having 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100% identity to the “KQNTLK” (SEQ ID NO: 111) peptide or the “QGALANIAVDKA” (SEQ ID NO: 110) peptide. 
     In a specific example, using as a base the six amino acid peptide “WQNTLK” (SEQ ID NO: 166) attached to the receptor by docking, a cavity detection was performed to identify the positions and binding site on the protein surface. In a specific example, with this information, a pharmacophore model was designed using the peptide geometrical structure and physical chemistry properties of the binding site. 
     In an embodiment, one or more small molecules were constructed iteratively using organic fragments databases (and/or other suitable databases) and/or genetic algorithms (and/or other suitable algorithms). In a specific example, the protein-molecule binding affinity was evaluated by a scoring function. In a specific example, then (and/or at any suitable time and frequency in any suitable order), de novo molecules were docked to the I2 receptor using the molecular docking methodology (but any suitable approaches can be used). In a specific example, later (and/or at any suitable time and frequency in any suitable order), de novo molecules were evaluated by different rules to select the best ligands based on ADME/T properties (absorption, distribution, metabolism, excretion, and toxicity), druggability and/or synthetic accessibility, and/or any suitable criteria can be used for selection. 
     Additionally or alternatively, a contact analysis between de novo molecules and the I2 protein can be performed with the objective of maintaining the interactions of the molecules with the amino acids reported in literature that are important in the binding with HLA-DR, as described in the previous section with peptides mutated. 
     In specific examples, such as according to any combination of the above, embodiments can include any suitable method, system, and/or therapeutic composition including and/or associated with (e.g., for determining, designing, generating, etc.) molecules to be protected as inhibitors of I2 superantigen meeting one or more of the following criteria:
         They are druggable molecules (e.g., meet Lipinski&#39;s rules; meet any suitable druggability rules),   They have a higher binding affinity for I2 protein than the original peptides from HLA binding zone (e.g., docking energies less than −6.8 kcal/mol; any suitable docking energies),   They have a molecular weight less than 500 g/mol (and/or any suitable molecular weight),   Their score of synthetic accessibility is less than 3 (and/or other suitable score) indicating that they are feasible to be synthesized, and/or   Compared with the original peptides, they maintain the main contacts (and/or any suitable contacts) with the I2 protein.       

     The region of interaction of the molecules with the I2 superantigen is depicted in  FIG. 8 . Molecules mol-1 to mol-7 are detailed in Table 8. 
     Embodiments (e.g., therapeutic compositions, etc.) can thus include and/or otherwise be associated with de novo small molecules to be protected as inhibitory compounds of I2 superantigen for Crohn&#39;s disease treatment or palliative treatment, including any one or more of the following compounds in pharmaceutically acceptable form or a pharmaceutically acceptable salt thereof: 
     
       
         
           
               
             
               
                 TABLE 8 
               
               
                   
               
               
                 Small molecules inhibiting I2 superantigen. 
               
               
                   
               
             
            
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
               
                   
               
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 Details of the contact interactions: 
               
            
           
           
               
               
            
               
                 Name 
                 Residues of I2 that interact with the protected small molecules 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 mol-1 
                 107 
                 108 
                 109 
                 11 
                 110 
                 12 
                 13 
                 14 
                 17 
                 18 
                 19 
                 21 
                 22 
                 26 
                 66 
                 69 
                 70 
                 72 
                 73 
                 76 
               
               
                   
                 SER 
                 GLY 
                 GLU 
                 THR 
                 ALA 
                 ASP 
                 PRO 
                 GLU 
                 ARG 
                 GLY 
                 LYS 
                 LEU 
                 GLN 
                 HIS 
                 VAL 
                 GLU 
                 THR 
                 HIS 
                 TYR 
                 ALA 
               
               
                 mol-2 
                 107 
                 108 
                 109 
                 11 
                 110 
                 13 
                 21 
                 22 
                 25 
                 26 
                 65 
                 66 
                 69 
                 70 
                 72 
                 73 
                 74 
                 76 
                 — 
                 — 
               
               
                   
                 SER 
                 GLY 
                 GLU 
                 THR 
                 ALA 
                 PRO 
                 LEU 
                 GLN 
                 ALA 
                 HIS 
                 ALA 
                 VAL 
                 GLU 
                 THR 
                 HIS 
                 TYR 
                 ASN 
                 ALA 
                   
                   
               
               
                 mol-3 
                 107 
                 11 
                 110 
                 21 
                 22 
                 26 
                 66 
                 69 
                 70 
                 72 
                 73 
                 76 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 SER 
                 THR 
                 ALA 
                 LEU 
                 GLN 
                 ALA 
                 VAL 
                 GLU 
                 THR 
                 HIS 
                 TYR 
                 ALA 
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 mol-4 
                 107 
                 108 
                 109 
                 11 
                 110 
                 13 
                 21 
                 22 
                 25 
                 26 
                 65 
                 66 
                 69 
                 70 
                 72 
                 73 
                 74 
                 76 
                 — 
                 — 
               
               
                   
                 SER 
                 GLY 
                 GLU 
                 THR 
                 ALA 
                 PRO 
                 LEU 
                 GLN 
                 ALA 
                 HIS 
                 ALA 
                 VAL 
                 GLU 
                 THR 
                 HIS 
                 TYR 
                 ASN 
                 ALA 
                   
                   
               
               
                 mol-5 
                 107 
                 108 
                 109 
                 11 
                 110 
                 18 
                 21 
                 22 
                 25 
                 65 
                 66 
                 69 
                 70 
                 72 
                 73 
                 76 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 SER 
                 GLY 
                 GLU 
                 THR 
                 ALA 
                 GLY 
                 LEU 
                 GLN 
                 ALA 
                 ALA 
                 VAL 
                 GLU 
                 THR 
                 HIS 
                 TYR 
                 ALA 
                   
                   
                   
                   
               
               
                 mol-6 
                 107 
                 108 
                 109 
                 110 
                 13 
                 19 
                 22 
                 23 
                 25 
                 26 
                 44 
                 45 
                 69 
                 70 
                 73 
                 — 
                 — 
                 — 
                 — 
                 — 
               
               
                   
                 SER 
                 GLY 
                 GLU 
                 ALA 
                 PRO 
                 LYS 
                 GLN 
                 THR 
                 ALA 
                 HIS 
                 ALA 
                 VAL 
                 GLU 
                 THR 
                 TYR 
                   
                   
                   
                   
                   
               
               
                 mol-7 
                 105 
                 106 
                 107 
                 108 
                 109 
                 11 
                 110 
                 18 
                 21 
                 22 
                 25 
                 26 
                 66 
                 69 
                 70 
                 73 
                 77 
                 — 
                 — 
                 — 
               
               
                   
                 GLY 
                 GLY 
                 SER 
                 GLY 
                 GLU 
                 THR 
                 ALA 
                 GLY 
                 LEU 
                 GLN 
                 ALA 
                 HIS 
                 VAL 
                 GLU 
                 THR 
                 TYR 
                 MET 
               
               
                   
               
            
           
         
       
     
     EXAMPLES 
     Example 1: Epitopes for Treating Peanut Allergy 
     As an example, from  Arachis hypogaea  (peanut) Ara-h allergen protein sequences, we predicted 58002 potential epitopes. These epitopes were filtered by rank, affinity, and removing duplicated sequences (and/or any suitable combination of approaches described herein; etc.), which resulted in an obtained 305 de novo epitopes. Those sub-database of sequences was aligned against  Clostridiales  bacteria  Fusicatenibacter  spp., a species eventually associated with peanut allergy, obtaining the final epitope “EEQGAIVTVRGGLRI” (SEQ ID NO: 167) (however, any suitable variation of the epitope sequence can be used in associated with approaches described herein; etc.). Epitopes that did not fit with the criteria described in Methodology section were discarded. The candidate epitope “EEQGAIVTVKGGLRI” (SEQ ID NO: 3), was reengineered obtaining better affinity with WIC receptor type II, mutating positions, 2, 3 and 5 by T, P and W, respectively. 
     Example 2: Epitopes Derived from  Arachis hypogaea  Ara-h Allergen Protein Sequences 
     From  Arachis hypogaea  Ara-h allergen protein sequences, we predicted 58002 potential epitopes from T cell Prediction Epitopes Pipeline (and/or suitable approaches described herein), where 1614 of them were high-ranked epitopes according scoring provided by each server. Duplicated sequences were discarded, then only 305 “de nova” epitopes resulted to be unique sequences. Then, this sequences were aligned against  Fusicatenibacter saccharivorans  and  Flavonifractor plautii . Consequently, we obtained six “common epitopes” between allergen sequences from  Arachis hypogaea  and  F. saccharivorans  (EEQGAIVTVRGGLRI (SEQ ID NO: 167), EQGAIVTVRGGLRIL (SEQ ID NO: 168), GLMSLSWMINFIRQV (SEQ ID NO: 169), LVALALFLLAAHASA (SEQ ID NO: 170), QGAIVTVRGGLRILS (SEQ ID NO: 171), TGNVASFLTSFSFEM (SEQ ID NO: 172)), and nine between  A. hypogaea  and  F. plautii  (ANYAYNYSVVGGVAL (SEQ ID NO: 173), FCIFFLILFLAQEYG (SEQ ID NO: 174), GFCIFFLILFLAQEY (SEQ ID NO: 175), GTIIGLAIATPVFTF (SEQ ID NO: 176), GTLLLFAGLALAGTL (SEQ ID NO: 177), LRRPFYSNAPQEIFI (SEQ ID NO: 178), NYAYNYSVVGGVALP (SEQ ID NO: 179), PAAITLALAAGGFLF (SEQ ID NO: 180), RRPFYSNAPQEIFIQ (SEQ ID NO: 181)). Epitopes that did not fit with the criteria described in Methodology section were discarded. However, any suitable criteria can be used. 
     Proteomes: 
       
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 Organisms, association, and taxonomy. 
               
            
           
           
               
               
               
               
               
            
               
                 NCBI 
                   
                   
                 Taxonomic 
                 Best Protein Match 
               
               
                 TaxaID 
                 Organism 
                 Association 
                 Order 
                 of Organism 
               
               
                   
               
               
                 292800 
                   Flavoni - 
                 Increased in 
                 
                   Clostridiales 
                 
                 Uncharacterized 
               
               
                   
                 
                   fractor 
                 
                 individuals 
                   
                 Protein 
               
               
                   
                 
                   plautii 
                 
                 with peanut 
                   
                 (Uniprot1D:G9YMO 
               
               
                   
                   
                 allergy 
                   
                 5) 
               
               
                 1150298 
                   Fusicateni - 
                 Decreased in 
                 
                   Clostridiales 
                 
                 Pyruvate phosphate 
               
               
                   
                 
                   bacter 
                 
                 individuals 
                   
                 dikinase 
               
               
                   
                   sacchari - 
                 with peanut 
                   
                 (Uniprot1D:AOA174 
               
               
                   
                 
                   vorans 
                 
                 allergy. 
                   
                 PZ33) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 11 
               
             
            
               
                   
               
               
                 Epitope origin and organism match. 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Found 
                   
                   
                   
                   
                 Docking 
               
               
                 Epi+31 
                 Aller+31 
                   
                   
                   
                 Pairwise 
                 results 
               
               
                 tope 
                 gen 
                 Organism 
                 %id 
                 %sim 
                 match 
                 (kcal/mol) 
               
               
                   
               
               
                 ANYA 
                 Arah8 
                 
                   F. plautii 
                 
                 75 
                 91.7 
                 12 
                 −7.2 
               
               
                 YNYS 
                   
                   
                   
                   
                   
                   
               
               
                 VVGG 
                   
                   
                   
                   
                   
                   
               
               
                 VAL 
                   
                   
                   
                   
                   
                   
               
               
                 (SEQ 
                   
                   
                   
                   
                   
                   
               
               
                 ID 
                   
                   
                   
                   
                   
                   
               
               
                 NO: 
                   
                   
                   
                   
                   
                   
               
               
                 173) 
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 NYAY 
                 Arah8 
                 
                   F. plautii 
                 
                 75 
                 91.7 
                 12 
                 −6.9 
               
               
                 NYSV 
                   
                   
                   
                   
                   
                   
               
               
                 VGGV 
                   
                   
                   
                   
                   
                   
               
               
                 ALP 
                   
                   
                   
                   
                   
                   
               
               
                 (SEQ 
                   
                   
                   
                   
                   
                   
               
               
                 ID 
                   
                   
                   
                   
                   
                   
               
               
                 NO: 
                   
                   
                   
                   
                   
                   
               
               
                 179) 
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 EQGA 
                 Arah3 
                   F. saccharivorans 
                 73 
                 90.9 
                 12 
                 −6.4 
               
               
                 IVTV 
                   
                   
                   
                   
                   
                   
               
               
                 RGGL 
                   
                   
                   
                   
                   
                   
               
               
                 RIL 
                   
                   
                   
                   
                   
                   
               
               
                 (SEQ 
                   
                   
                   
                   
                   
                   
               
               
                 ID 
                   
                   
                   
                   
                   
                   
               
               
                 NO: 
                   
                   
                   
                   
                   
                   
               
               
                 168) 
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 EEQG 
                 Arah3 
                   F. saccharivorans 
                 73 
                 90.9 
                 12 
                 −7.2 
               
               
                 AIVT 
                   
                   
                   
                   
                   
                   
               
               
                 VRGG 
                   
                   
                   
                   
                   
                   
               
               
                 LRI 
                   
                   
                   
                   
                   
                   
               
               
                 (SEQ 
                   
                   
                   
                   
                   
                   
               
               
                 ID 
                   
                   
                   
                   
                   
                   
               
               
                 NO: 
                   
                   
                   
                   
                   
                   
               
               
                 167) 
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                 QGAI 
                 Arah3 
                   F. saccharivorans 
                 73 
                 90.9 
                 12 
                 −5.8 
               
               
                 VTVR 
                   
                   
                   
                   
                   
                   
               
               
                 GGLR 
                   
                   
                   
                   
                   
                   
               
               
                 ILS 
                   
                   
                   
                   
                   
                   
               
               
                 (SEQ 
                   
                   
                   
                   
                   
                   
               
               
                 ID 
                   
                   
                   
                   
                   
                   
               
               
                 NO: 
                   
                   
                   
                   
                   
                   
               
               
                 171) 
               
               
                   
               
            
           
         
       
     
     Finally (and/or at any suitable time and frequency), to classify “common epitopes” according their affinity to the receptor, we ran docking simulations of 5 filtered de-nova epitopes from Arah-type allergens against HLA-DPB1; a MEC class II receptor structure (PDB code: 3LQZ). 
     In specific examples to find an improvement of best epitopes, epitopes can be evaluated through a re-engineering process, consisting of sequential mutation in-silica and considering the other 19 amino acids, one at the time, by checking their effect over the docking affinity. As an example one of the inverse associated (EEQGAIVTVKGGLRI (SEQ ID NO: 3), docking energy: −7.2 kcal/mol) and one of associated organism (NYANYSVVGGVALP (SEQ ID NO: 182), docking energy: −6.9 kcal/mol) wild-type epitopes were re-engineered with values of binding energy obtained from docking results, described in Table 12 and Table 13 respectively. Bold letters represent single mutation that improves the most the energy over the WT epitope. 
     
       
         
           
               
             
               
                 TABLE 12 
               
             
            
               
                   
               
               
                 Docking results for the reengineering epitope EEQGAIVTVKGGLRI (SEQ ID NO: 3) 
               
            
           
           
               
               
            
               
                   
                 EEOGAIVTVKGGLRI Docking Values of single mutants (kcal/mol) 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
                 7 
                 8 
                 9 
                 10 
                 11 
                 12 
                 13 
                 14 
                 15 
               
               
                 AA 
                 E 
                 E 
                 Q 
                 G 
                 A 
                 I 
                 V 
                 T 
                 V 
                 K 
                 G 
                 G 
                 L 
                 R 
                 I 
               
               
                   
               
               
                 A 
                 −5.6 
                 −5.9 
                 −6.3 
                 −6.2 
                 − 
                 −6.4 
                 −5.6 
                 −6.5 
                 −6.8 
                 −4.7 
                 −6.2 
                 −6.0 
                 −6.1 
                 −6.4 
                 −6.7 
               
               
                   
               
               
                 C 
                 −6.5 
                 −5.6 
                 −6.5 
                 −6.3 
                 −6.8 
                 −6.4 
                 −4.4 
                 −6.6 
                 −6.1 
                 −6.4 
                 −6.4 
                 −6.0 
                 −4.9 
                 −6.2 
                 −6.5 
               
               
                   
               
               
                 D 
                 −6.6 
                 −5.9 
                 −5.9 
                 −6.2 
                 −6.1 
                 −6.4 
                 4.3 
                 −5.6 
                 −7.1 
                 −6.3 
                 −6.4 
                 −6.5 
                 −6.4 
                 −5.9 
                 −6.7 
               
               
                   
               
               
                 E 
                 − 
                 − 
                 −6.3 
                 −6.3 
                 −4.7 
                 −6.8 
                 −6.4 
                 −4.9 
                 −6.0 
                 −6.9 
                 −6.1 
                 −5.8 
                 −6.8 
                 −5.3 
                 −6.6 
               
               
                   
               
               
                 F 
                 −6.9 
                 −5.8 
                 −6.5 
                 −6.3 
                 −6.0 
                 −5.4 
                 −6.5 
                 −6.5 
                 −6.2 
                 −6.3 
                 −5.8 
                 −6.7 
                 −6.5 
                 −6.4 
                 −6.6 
               
               
                   
               
               
                 G 
                 −6.7 
                 −6.4 
                 −6.2 
                 − 
                 −6.2 
                 −6.4 
                 −6.6 
                 −5.7 
                 −6.0 
                 −6.0 
                 − 
                 − 
                 −5.6 
                 −6.2 
                 −6.1 
               
               
                   
               
               
                 H 
                 −64 
                 −6.0 
                 −6.1 
                 −6.8 
                 −6.3 
                 −5.9 
                 −6.4 
                 −6.6 
                 −6.5 
                 −5.9 
                 −5.9 
                 −6.5 
                 −5.8 
                 −5.1 
                 −7.9 
               
               
                   
               
               
                 I 
                 −5.4 
                 −6.1 
                 −5.2 
                 −5.1 
                 −6.2 
                 − 
                 −6.2 
                 −6.5 
                 −6.1 
                 −5.5 
                 −5.3 
                 −5.8 
                 −5.6 
                 −5.3 
                 − 
               
               
                   
               
               
                 K 
                 −5.9 
                 −5.7 
                 −5.8 
                 −6.6 
                 −6.4 
                 −6.0 
                 −6.2 
                 −5.5 
                 −6.0 
                 − 
                 −6.6 
                 −5.6 
                 −5.9 
                 −6.0 
                 −4.9 
               
               
                   
               
               
                 L 
                 −7.0 
                 −5.1 
                 −6.9 
                 −6.1 
                 −5.2 
                 −6.3 
                 −5.5 
                 −5.6 
                 −6.6 
                 −6.0 
                 −6.2 
                 −6.6 
                 − 
                 −6.4 
                 −6.3 
               
               
                   
               
               
                 M 
                 −6.7 
                 −5.9 
                 −6.9 
                 −6.2 
                 −6.1 
                 −6.1 
                 −6.4 
                 −5.8 
                 −6.1 
                 −6.1 
                 −5.8 
                 −5.3 
                 −6.4 
                 −5.9 
                 −6.6 
               
               
                   
               
               
                 N 
                 −6.3 
                 −6.2 
                 −5.6 
                 −5.1 
                 −5.6 
                 −6.2 
                 −5.8 
                 −6.2 
                 −6.3 
                 −6.4 
                 −6.4 
                 −6.3 
                 −6.9 
                 −6.4 
                 −6.5 
               
               
                   
               
               
                 P 
                 −6.7 
                 −5.9 
                 −8.5 
                 −5.2 
                 −6.5 
                 −7.1 
                 −5.9 
                 −6.3 
                 −4.5 
                 −5.9 
                 −5.3 
                 −7.0 
                 −6.7 
                 −6.1 
                 −6.0 
               
               
                   
               
               
                 Q 
                 −6.0 
                 −5.8 
                 − 
                 −5.6 
                 −5.8 
                 −6.5 
                 −5.8 
                 −5.6 
                 −6.2 
                 −6.9 
                 −7.3 
                 −6.4 
                 −6.3 
                 −6.0 
                 −6.8 
               
               
                   
               
               
                 R 
                 −6.5 
                 −6.6 
                 −5.8 
                 −5.0 
                 −5.5 
                 −6.3 
                 −6.2 
                 −5.9 
                 −4.9 
                 −5.6 
                 −5.0 
                 −6.8 
                 −4.7 
                 − 
                 −5.5 
               
               
                   
               
               
                 S 
                 −5.8 
                 −6.2 
                 −5.4 
                 −5.9 
                 −6.1 
                 −6.2 
                 −6.3 
                 −6.1 
                 −6.6 
                 −5.9 
                 −6.9 
                 −6.4 
                 −5.5 
                 −5.1 
                 −6.0 
               
               
                   
               
               
                 T 
                 −6.4 
                 −7.2 
                 −6.8 
                 −5.8 
                 −5.6 
                 −6.4 
                 −5.3 
                 − 
                 −5.2 
                 −6.2 
                 −6.6 
                 −6.2 
                 −6.6 
                 −7.0 
                 −6.0 
               
               
                   
               
               
                 V 
                 −6.3 
                 −5.2 
                 −5.9 
                 −6.6 
                 −5.7 
                 −6.2 
                 − 
                 −6.3 
                 − 
                 −4.4 
                 −5.9 
                 −6.2 
                 −6.1 
                 −6.6 
                 −6.3 
               
               
                   
               
               
                 W 
                 −6.6 
                 −6.3 
                 −6.4 
                 −6.1 
                 −7.3 
                 −6.6 
                 −5.4 
                 −6.5 
                 −5.1 
                 −6.1 
                 −5.9 
                 −6.9 
                 −6.3 
                 −6.3 
                 −8.1 
               
               
                   
               
               
                 Y 
                 −6.4 
                 −7.0 
                 −6.9 
                 −6.2 
                 −5.8 
                 −6.4 
                 −6.7 
                 −6.7 
                 −5.6 
                 −6.1 
                 −6.1 
                 −6.5 
                 −6.2 
                 −5.9 
                 −6.2 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 13 
               
             
            
               
                   
               
               
                 Docking results for the reengineering epitope NYAYNYSVVGGVALP (SEQ ID NOL 179) 
               
            
           
           
               
               
            
               
                   
                 NYAYNYSWGGVALP Docking values of single mutants (kcal/mol) 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 1 
                 2 
                 3 
                 4 
                 5 
                 6 
                 7 
                 8 
                 9 
                 10 
                 11 
                 12 
                 13 
                 14 
                 15 
               
               
                 AA 
                 N 
                 Y 
                 A 
                 Y 
                 N 
                 Y 
                 S 
                 V 
                 V 
                 G 
                 G 
                 V 
                 A 
                 L 
                 P 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 A 
                 −6.9 
                 −6.5 
                 — 
                 −6.8 
                 −7.4 
                 −7.3 
                 −7.5 
                 −7.0 
                 −6.9 
                 −8.0 
                 −9.1 
                 −7.3 
                 — 
                 −7.0 
                 −6.2 
               
               
                   
               
               
                 C 
                 −7.6 
                 −7.4 
                 −17.3 
                 −7.6 
                 −6.8 
                 −7.2 
                 −7.3 
                 −6.6 
                 −7.3 
                 −6.4 
                 −7.1 
                 −6.3 
                 −8.1 
                 −6.8 
                 −6.6 
               
               
                   
               
               
                 D 
                 −7.1 
                 −6.7 
                 −6.8 
                 −7.0 
                 −7.9 
                 −6.9 
                 −6.5 
                 −6.8 
                 −7.2 
                 −6.4 
                 −5.0 
                 −7.7 
                 −7.1 
                 −7.2 
                 −8.1 
               
               
                   
               
               
                 E 
                 −6.7 
                 −5.8 
                 −7.0 
                 −5.7 
                 −6.7 
                 −7.4 
                 −6.7 
                 −7.1 
                 −6.9 
                 −6.9 
                 −6.0 
                 −8.3 
                 −6.4 
                 −6.8 
                 −6.8 
               
               
                   
               
               
                 F 
                 −8.0 
                 −7.4 
                 −6.9 
                 −6.9 
                 −6.8 
                 −7.5 
                 −7.4 
                 −6.4 
                 −7.3 
                 −7.0 
                 −7.5 
                 −6.4 
                 −6.7 
                 −7.0 
                 −8.0 
               
               
                   
               
               
                 G 
                 −7.0 
                 −7.8 
                 −7.8 
                 −5.9 
                 −6.2 
                 −7.0 
                 −6.1 
                 −5.8 
                 −7.7 
                 — 
                 — 
                 −6.7 
                 −7.3 
                 −8.0 
                 −6.1 
               
               
                   
               
               
                 H 
                 −8.2 
                 −7.0 
                 −6.9 
                 −7.0 
                 −7.9 
                 −6.8 
                 −6.0 
                 −7.6 
                 −7.6 
                 −8.3 
                 −6.4 
                 −7.1 
                 −7.6 
                 −7.4 
                 −7.9 
               
               
                   
               
               
                 I 
                 −6.7 
                 −6.3 
                 −8.2 
                 −7.0 
                 −6.9 
                 −5.7 
                 −7.5 
                 −7.1 
                 −6.1 
                 −7.2 
                 −6.9 
                 −5.9 
                 −6.6 
                 −6.7 
                 −7.6 
               
               
                   
               
               
                 K 
                 −6.7 
                 −6.6 
                 −8.1 
                 −7.4 
                 −7.2 
                 −6.3 
                 −5.9 
                 −7.1 
                 −7.4 
                 −7.2 
                 −9.0 
                 −7.6 
                 −5.5 
                 −6.4 
                 −7.6 
               
               
                   
               
               
                 L 
                 −7.3 
                 −7.4 
                 −7.3 
                 −7.2 
                 −8.7 
                 −8.3 
                 −7.2 
                 −8.4 
                 −7.1 
                 −7.6 
                 −6.9 
                 −6.6 
                 −8.2 
                 — 
                 −6.4 
               
               
                   
               
               
                 M 
                 −7.2 
                 −7.0 
                 −5.9 
                 −7.4 
                 −7.6 
                 −5.8 
                 −6.2 
                 −7.6 
                 −6.8 
                 −6.4 
                 −7.3 
                 −6.9 
                 −6.4 
                 −7.3 
                 −7.1 
               
               
                   
               
               
                 N 
                 — 
                 −7.8 
                 −6.4 
                 −7.6 
                 — 
                 −4.9 
                 −7.8 
                 −6.2 
                 −7.5 
                 −7.0 
                 −7.3 
                 −7.1 
                 −6.3 
                 −7.3 
                 −6.7 
               
               
                   
               
               
                 P 
                 −7.4 
                 −6.6 
                 −5.5 
                 −6.3 
                 −6.9 
                 −7.1 
                 −7.5 
                 −7.9 
                 −6.6 
                 −7.1 
                 −6.6 
                 −6.3 
                 −7.7 
                 −7.0 
                 — 
               
               
                   
               
               
                 Q 
                 −5.8 
                 −6.4 
                 −7.1 
                 −7.8 
                 −7.8 
                 −6.1 
                 −6.9 
                 −7.4 
                 −8.7 
                 −8.9 
                 −7.9 
                 −6.0 
                 −6.8 
                 −6.8 
                 −6.5 
               
               
                   
               
               
                 R 
                 −7.7 
                 −6.1 
                 −6.4 
                 −6.9 
                 −6.4 
                 −7.0 
                 −79 
                 −9.3 
                 −6.8 
                 −8.1 
                 −7.3 
                 −6.7 
                 −7.6 
                 −7.4 
                 −6.7 
               
               
                   
               
               
                 S 
                 −7.3 
                 −5.4 
                 −7.8 
                 −7.2 
                 −9.4 
                 −6.8 
                 — 
                 −6.6 
                 −6.7 
                 −7.2 
                 −7.2 
                 −8.0 
                 −7.1 
                 −7.8 
                 −5.5 
               
               
                   
               
               
                 T 
                 −8.9 
                 −7.6 
                 −7.5 
                 −6.4 
                 −7.4 
                 −6.9 
                 −7.1 
                 −5.7 
                 −9.3 
                 −6.7 
                 −7.4 
                 −5.9 
                 −6.5 
                 −7.7 
                 −7.1 
               
               
                   
               
               
                 V 
                 −6.8 
                 −7.9 
                 −6.2 
                 −6.2 
                 −7.0 
                 −7.1 
                 −8.0 
                 — 
                 — 
                 −7.4 
                 −8.1 
                 — 
                 −11.0 
                 −6.2 
                 −6.8 
               
               
                   
               
               
                 W 
                 −6.9 
                 −6.9 
                 −6.4 
                 −6.6 
                 −6.9 
                 −6.9 
                 −7.5 
                 −7.1 
                 −7.7 
                 −6.6 
                 −7.5 
                 −7.3 
                 −6.8 
                 −8.1 
                 −6.9 
               
               
                   
               
               
                 Y 
                 −8.1 
                 — 
                 −7.1 
                 — 
                 −6.3 
                 — 
                 −7.0 
                 −7.2 
                 −6.8 
                 −7.2 
                 −8.8 
                 −6.6 
                 −7.5 
                 −8.8 
                 −5.9 
               
               
                   
               
            
           
         
       
     
     In specific examples according to the Table and criteria, improved reengineered epitopes obtained with better binding energy compared with wild type can include those with the following patterns: 
     
       
         
           
               
               
            
               
                   
                 Epitope: 
               
               
                   
                 (SEQ ID NO: 3) 
               
               
                   
                 EEQGAIVTVKGGLRI 
               
            
           
         
       
     
     2: T 
     3: P 
     5: W 
     11: Q 
     15: H, W 
     
       
         
           
               
               
            
               
                   
                 Epitope: 
               
               
                   
                 (SEQ ID NO: 179) 
               
               
                   
                 NYAYNYSVVGGVALP 
               
            
           
         
       
     
     1: A, C, D, F, G, H, L, M, P, R, S, T, W, Y 
     2: C, F, G, H, L, M, N, T, V, W 
     3: C, E, F, G, H, I, K, L, Q, S, T, Y 
     4: C, D, F, H, I, K, L, M, N, Q, R, S 
     5: A, D, H, I, K, L, M, P, Q, S, T, V, W 
     6: A, C, D, E, F, G, L, P, R, T, V, W 
     7: A, C, F, I, L, N, P, Q, R, T, V, W, Y 
     8: A, E, H, I, K, L, M, P, Q, R, W, Y 
     9: A, C, D, E, F, G, H, K, L, N, Q, T, W 
     10: A, E, F, H, I, K, L, N, P, Q, R, S, V, Y 
     11: A, C, F, I, K, L, M, N, Q, R, S, T, V, W, Y 
     12: A, D, E, H, K, M, N, S, W 
     13: C, D, G, H, L, P, R, S, V, Y 
     14: A, D, F, G, H, M, N, P, R, S, T, W, Y 
     15: D, F, H, I, K, M, T, W 
     
       
         
           
               
             
               
                 TABLE 14 
               
               
                   
               
               
                 Additional or alternative examples of epitopes 
               
               
                 that might be reengineered: 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                 AKLTILVALALFLLA 
                 ATPLLVIFSPILVPA 
                 ASLKFAFVMLVCMAM 
               
               
                 (SEQ ID NO: 183) 
                 (SEQ ID NO: 184) 
                 (SEQ ID NO: 185) 
               
               
                   
               
               
                 ATPVFTFFSPVIVPA 
                 CIFFLILFLAQEYGV 
                 MAKLT1LVALALFLL 
               
               
                 (SEQ ID NO: 186) 
                 (SEQ ID NO: 187) 
                 (SEQ ID NO: 188) 
               
               
                   
               
               
                 CIFFLVLFLAQEGVV 
                 MASLKFAFVMLVCMA 
                 MIDFEEFRVMMMMGS 
               
               
                 (SEQ ID NO: 189) 
                 (SEQ ID NO: 190) 
                 (SEQ ID NO: 191) 
               
               
                   
               
               
                 DFEEFRVMMMMGSRH 
                 MMVKLSILVALLGAL 
                 DGMIDFEEFRVMMMM 
               
               
                 (SEQ ID NO: 192) 
                 (SEQ ID NO: 193) 
                 (SEQ ID NO: 194) 
               
               
                   
               
               
                 DGYISLQEFIELNTK 
                 MVKLSILVALLGALL 
                 FEEFRVMMMMGSRHD 
               
               
                 (SEQ ID NO: 195) 
                 (SEQ ID NO: 196) 
                 (SEQ ID NO: 197) 
               
               
                   
               
               
                 NIFSGFTPEFLEQAF 
                 FFLILFLAQEYGVEG 
                 NPFKFFVPPFQQSPR 
               
               
                 (SEQ ID NO: 198) 
                 (SEQ ID NO: 199) 
                 (SEQ ID NO: 200) 
               
               
                   
               
               
                 FFLVLFLAQEGVVKT 
                 PLFILFSPVIVPATI 
                 FLILFLAQEYGVEGK 
               
               
                 (SEQ ID NO: 201) 
                 (SEQ ID NO: 202) 
                 (SEQ ID NO: 203) 
               
               
                   
               
               
                 PVFIFFSPVIVPAW 
                 FLVLFLAQEGWKTE 
                 PVFTFFSPVIVPAVV 
               
               
                 (SEQ ID NO: 204) 
                 (SEQ ID NO: 205) 
                 (SEQ ID NO: 206) 
               
               
                   
               
               
                 FSGFAQEFLQHAFQV 
                 QAIKFMTASTIGVSF 
                 FSGFTPEFLAQAFQV 
               
               
                 (SEQ ID NO: 207) 
                 (SEQ ID NO: 208) 
                 (SEQ ID NO: 209) 
               
               
                   
               
               
                 RQAIKFMTASTIGVS 
                 GFAQEFLQHAFQVDR 
                 SGFAQEFLQHAFQVD 
               
               
                 (SEQ ID NO: 210) 
                 (SEQ ID NO: 211) 
                 (SEQ ID NO: 212) 
               
               
                   
               
               
                 GFCIFFLILFLAQEY 
                 SGFTPEFLAQAFQVD 
                 GSNIFSGFAQEFLQH 
               
               
                 (SEQ ID NO: 213) 
                 (SEQ ID NO: 214) 
                 (SEQ ID NO: 215) 
               
               
                   
               
               
                 TGGTLLLLSGLSLLG 
                 GTLLLLSGLSLLGTI 
                 TGTVIGLIIATPLLV 
               
               
                 (SEQ ID NO: 216) 
                 (SEQ ID NO: 217) 
                 (SEQ ID NO: 218) 
               
               
                   
               
               
                 IFFLILFLAQEYGVE 
                 TPLFILFSPVIVPAI 
                 IFFLVLFLAQEGVVK 
               
               
                 (SEQ ID NO: 219) 
                 (SEQ ID NO: 220) 
                 (SEQ ID NO: 221) 
               
               
                   
               
               
                 TPLLVIFSPILVPAA 
                 IFSGFTPEFLEQAFQ 
                 TPVFIFFSPVIVPAV 
               
               
                 (SEQ ID NO: 222) 
                 (SEQ ID NO: 223) 
                 (SEQ ID NO: 224) 
               
               
                   
               
               
                 IRQAIKFMTASTIGV 
                 TPVFTFF SPVIVPAV 
                 KLSILVALLGALLW 
               
               
                 (SEQ ID NO: 225) 
                 (SEQ ID NO: 226) 
                 (SEQ ID NO: 227) 
               
               
                   
               
               
                 TTPLFILFSPVIVPA 
                 LMSLSWMINFIRQVH 
                 TVIGLIIATPLLVIF 
               
               
                 (SEQ ID NO: 228) 
                 (SEQ ID NO: 229) 
                 (SEQ ID NO: 230) 
               
               
                   
               
               
                 LNLLILRWLGLSAEY 
                 VKLSILVALLGALLV 
                 LSSFSWVMNYIRQTH 
               
               
                 (SEQ ID NO: 231) 
                 (SEQ ID NO: 232) 
                 (SEQ ID NO: 233)