Predicting class II MHC-Peptide binding:a kernel based approach using similarity scores

Background - Modelling the interaction between potentially antigenic peptides and Major Histocompatibility Complex (MHC) molecules is a key step in identifying potential T-cell epitopes. For Class II MHC alleles, the binding groove is open at both ends, causing ambiguity in the positional alignment between the groove and peptide, as well as creating uncertainty as to what parts of the peptide interact with the MHC. Moreover, the antigenic peptides have variable lengths, making naive modelling methods difficult to apply. This paper introduces a kernel method that can handle variable length peptides effectively by quantifying similarities between peptide sequences and integrating these into the kernel. Results - The kernel approach presented here shows increased prediction accuracy with a significantly higher number of true positives and negatives on multiple MHC class II alleles, when testing data sets from MHCPEP [1], MCHBN [2], and MHCBench [3]. Evaluation by cross validation, when segregating binders and non-binders, produced an average of 0.824 AROC for the MHCBench data sets (up from 0.756), and an average of 0.96 AROC for multiple alleles of the MHCPEP database. Conclusion - The method improves performance over existing state-of-the-art methods of MHC class II peptide binding predictions by using a custom, knowledge-based representation of peptides. Similarity scores, in contrast to a fixed-length, pocket-specific representation of amino acids, provide a flexible and powerful way of modelling MHC binding, and can easily be applied to other dynamic sequence problems.

Toward prediction of class II mouse major histocompatibility complex peptide binding affinity:in silico bioinformatic evaluation using partial least squares, a robust multivariate statistical technique

The accurate identification of T-cell epitopes remains a principal goal of bioinformatics within immunology. As the immunogenicity of peptide epitopes is dependent on their binding to major histocompatibility complex (MHC) molecules, the prediction of binding affinity is a prerequisite to the reliable prediction of epitopes. The iterative self-consistent (ISC) partial-least-squares (PLS)-based additive method is a recently developed bioinformatic approach for predicting class II peptide−MHC binding affinity. The ISC−PLS method overcomes many of the conceptual difficulties inherent in the prediction of class II peptide−MHC affinity, such as the binding of a mixed population of peptide lengths due to the open-ended class II binding site. The method has applications in both the accurate prediction of class II epitopes and the manipulation of affinity for heteroclitic and competitor peptides. The method is applied here to six class II mouse alleles (I-Ab, I-Ad, I-Ak, I-As, I-Ed, and I-Ek) and included peptides up to 25 amino acids in length. A series of regression equations highlighting the quantitative contributions of individual amino acids at each peptide position was established. The initial model for each allele exhibited only moderate predictivity. Once the set of selected peptide subsequences had converged, the final models exhibited a satisfactory predictive power. Convergence was reached between the 4th and 17th iterations, and the leave-one-out cross-validation statistical terms - q2, SEP, and NC - ranged between 0.732 and 0.925, 0.418 and 0.816, and 1 and 6, respectively. The non-cross-validated statistical terms r2 and SEE ranged between 0.98 and 0.995 and 0.089 and 0.180, respectively. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method is available commercially in the SYBYL molecular modeling software package. The resulting models, which can be used for accurate T-cell epitope prediction, will be made freely available online (http://www.jenner.ac.uk/MHCPred).

Towards the in silico identification of class II restricted T-cell epitopes:a partial least squares iterative self-consistent algorithm for affinity prediction

Motivation: The immunogenicity of peptides depends on their ability to bind to MHC molecules. MHC binding affinity prediction methods can save significant amounts of experimental work. The class II MHC binding site is open at both ends, making epitope prediction difficult because of the multiple binding ability of long peptides. Results: An iterative self-consistent partial least squares (PLS)-based additive method was applied to a set of 66 pep- tides no longer than 16 amino acids, binding to DRB1*0401. A regression equation containing the quantitative contributions of the amino acids at each of the nine positions was generated. Its predictability was tested using two external test sets which gave r pred =0.593 and r pred=0.655, respectively. Furthermore, it was benchmarked using 25 known T-cell epitopes restricted by DRB1*0401 and we compared our results with four other online predictive methods. The additive method showed the best result finding 24 of the 25 T-cell epitopes. Availability: Peptides used in the study are available from http://www.jenner.ac.uk/JenPep. The PLS method is available commercially in the SYBYL molecular modelling software package. The final model for affinity prediction of peptides binding to DRB1*0401 molecule is available at http://www.jenner.ac.uk/MHCPred. Models developed for DRB1*0101 and DRB1*0701 also are available in MHC- Pred

EpiDOCK:a molecular docking-based tool for MHC class II binding prediction

Cellular peptide vaccines contain T-cell epitopes. The main prerequisite for a peptide to act as a T-cell epitope is that it binds to a major histocompatibility complex (MHC) protein. Peptide MHC binder identification is an extremely costly experimental challenge since human MHCs, named human leukocyte antigen, are highly polymorphic and polygenic. Here we present EpiDOCK, the first structure-based server for MHC class II binding prediction. EpiDOCK predicts binding to the 23 most frequent human, MHC class II proteins. It identifies 90% of true binders and 76% of true non-binders, with an overall accuracy of 83%. EpiDOCK is freely accessible at http://epidock.ddg-pharmfac. net. © The Author 2013. Published by Oxford University Press. All rights reserved.

MHC class II binding prediction by molecular docking

Proteins of the Major Histocompatibility Complex (MHC) bind self and nonself peptide antigens or epitopes within the cell and present them at the cell surface for recognition by T cells. All T-cell epitopes are MHC binders but not all MCH binders are T-cell epitopes. The MHC class II proteins are extremely polymorphic. Polymorphic residues cluster in the peptide-binding region and largely determine the MHC's peptide selectivity. The peptide binding site on MHC class II proteins consist of five binding pockets. Using molecular docking, we have modelled the interactions between peptide and MHC class II proteins from locus DRB1. A combinatorial peptide library was generated by mutation of residues at peptide positions which correspond to binding pockets (so called anchor positions). The binding affinities were assessed using different scoring functions. The normalized scoring functions for each amino acid at each anchor position were used to construct quantitative matrices (QM) for MHC class II binding prediction. Models were validated by external test sets comprising 4540 known binders. Eighty percent of the known binders are identified in the best predicted 15% of all overlapping peptides, originating from one protein. © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Major Histocompatibility Complex (MHC) Class II sequence polymorphism in long-finned pilot whale (Globicephala melas) from the North Atlantic

Funding Silvia S. Monteiro and Marisa Ferreira were supported by a Ph.D. grant from Fundação para a Ciência e Tecnologia (ref SFRH/BD/38735/2007 and SFRH/BD/30240/2006, respectively). Alfredo López was supported by a postdoctoral grant from Fundação para a Ciência e Tecnologia (ref SFRH/BPD/82407/2011). Catarina Eira is supported by CESAM (UID/AMB/50017), from FCT/MEC through national funds and FEDER (PT2020, Compete 2020). The work related with strandings and tissue collection in Portugal was partially supported by the SafeSea Project EEAGrants PT 0039 (supported by Iceland, Liechtenstein and Norway through the EEA Financial Mechanism), by the Project MarPro–Life09 NAT/PT/000038 (funded by the European Union–Program Life+) and by the project CetSenti FCT RECI/AAG-GLO/0470/2012; FCOMP-01-0124-FEDER-027472 (Funded by the Program COMPETE and Fundação para a Ciência e Tecnologia).

Two years survival rate of Class II ART restorations in primary molars using two ways to avoid saliva contamination

AIM To compare the survival rates of Class II Atraumatic Restorative Treatment (ART) restorations placed in primary molars using cotton rolls or rubber dam as isolation methods. METHODS A total of 232 children, 6-7 years old, both genders, were selected having one primary molar with proximal dentine lesion. The children were randomly assigned into two groups: control group with Class II ART restoration made using cotton rolls and experimental group using rubber dam. The restorations were evaluated by eight calibrated evaluators (Kappa > 0.8) after 6, 12, 18 and 24 months. RESULTS A total of 48 (20.7%) children were considered dropout, after 24 months. The cumulative survival rate after 6, 12, 18 and 24 months was 61.4%, 39.0%, 29.1% and 18.0%, respectively for the control group, and 64.1%, 55.1%, 40.1% and 32.1%, respectively for the rubber dam group. The log rank test for censored data showed no statistical significant difference between the groups (P = 0.07). The univariate Cox Regression showed no statistical significant difference after adjusting for independent variables (P > 0.05). CONCLUSION Both groups had similar survival rates, and after 2 years, the use of rubber dam does not increase the success of Class II ART restorations significantly.

Correlation between morphology and function of the upper lip: a longitudinal evaluation

In order to evaluate the relationship between the morphology of the upper lip and muscle activity in a sample of 38 subjects (17 males and 21 females) with Angle Class II division 1 malocclusions, cephalometric and electromyographic analyses were conducted. The sample was subdivided into either predominantly nose or mouth breathers. The individuals were evaluated at two different periods, with a 2 year interval. At the first observation, the subjects were 11 years to 14 years 11 months of age and at the second observation, 13 years 4 months to 16 years 6 months of age. Height and thickness of the upper lip were measured on lateral cephalograms with the aid of a digital pachymeter. For each individual, electromyographic records were obtained of the orbicularis oris superior muscle at rest and in a series of 12 movements. The electromyographic data were normalized as a function of amplitude, for achievement of the percentage value of each movement. Pearson and Spearman correlation tests were applied.The results showed some correlation between morphology and muscle function (at a confidence level of 95 per cent). However, as the values of the correlation coefficient (r) were too low to establish associations between variables, it was concluded that the dimensions of the upper lip are not correlated with muscle activity.

Influence of intentional ankylosis of deciduous canines to reinforce the anchorage for maxillary protraction

INTRODUÇÃO: nesse estudo cefalométrico retrospectivo, analisou-se a influência da anquilose intencional de caninos decíduos em pacientes com má oclusão de Classe III e mordida cruzada anterior, nos estágios de dentição decídua e mista precoce, tratados com expansão ortopédica da maxila, seguida de tração reversa. MÉTODOS: foram utilizadas telerradiografias em norma lateral de 40 pacientes, divididos em 2 grupos pareados por idade e sexo. O Grupo Anquilose foi constituído de 20 pacientes (10 meninos e 10 meninas) tratados com anquilose induzida e que apresentavam as idades médias inicial e final, respectivamente, de 7a 4m e 8a 3m, e o tempo médio de tração reversa de 11 meses. O Grupo Controle, composto de 20 pacientes (10 meninos e 10 meninas) tratados sem anquilose induzida e que apresentavam as idades médias inicial de 7a 8m e final de 8a 7m, e tempo médio de tração reversa de 11 meses. Foram empregadas as análises de Variância a dois critérios e de Covariância para comparar as variáveis cefalométricas inicial e final e as alterações de tratamento entre os grupos. RESULTADOS: segundo os resultados, as variáveis que evidenciaram as mudanças de tratamento significativas entre os grupos confirmaram que o procedimento de anquilose intencional potencializou a resposta sagital das bases apicais (Pg-NPerp) e aumentou os ângulos de convexidade facial (NAP e ANB). CONCLUSÃO: o protocolo envolvendo a anquilose intencional de caninos decíduos potencializou a resposta sagital das bases apicais.

Maxillary and mandibular width changes studied using metallic implants.

The purpose of this implant study was to evaluate the transverse stability of the basal maxillary and mandibular structures. The sample included 25 subjects between 12 and 18 years of age who were followed for approximately 2.6 years. Metallic implants were placed bilaterally into the maxillary and mandibular corpora before treatment. Once implant stability had been confirmed, treatment (4 first premolar extractions followed by fixed appliance therapy) was initiated. Changes in the transverse maxillary and mandibular implants were evaluated cephalometrically and two groups (GROW+ and GROW++; selection based on growth changes in facial height and mandibular length) were compared. The GROW++ group showed significant width increases of the posterior maxillary implants (P <.001) and the mandibular implants (P =.009); there was no significant change for the anterior maxillary implants. The GROW+ group showed no significant width changes between the maxillary and mandibular implants. We conclude that (1) there are significant width increases during late adolescence of the basal mandibular and maxillary skeletal structures and (2) the width changes are related with growth potential.

Diagnóstico e tratamento precoce da Classe III: relato de um caso clínico

In malocclusion studies, may happen not only dental discrepancies but even skeletal discrepancies. In Class III malocclusion can be observed underdeveloped maxilla, mandible protraction or both of them, and, in most of the times associated with a narrow maxilla that causes anterior or posterior crossbites, in one side or in two sides. The aim of this case report is to evaluate the facial profile and occlusal effects of interceptive orthodontics therapy. The treatment with upper arch expansion and maxilla protraction was done in an early age to be effective in the circummaxillary sutural system and to make the orthopedic effect easier. The facial mask used is positioned on two facial points and allows an anterior maxillary replacement. Patients’ compliance is important to reach treatment success, this because using the mask still in this growth and development phase is essential to make the facial and occlusal effects happen. It is important to mention that patients with Angle Class III malocclusion need to be followed till the end of their growth.

Tratamento compensatorio da má oclusnao de classe lll: revisão de literatura

Class III malocclusion is less common occlusal relationship, covering less than 5% of the population. There are various forms of treatment in Class III malocclusion. Depending on how the form is expressed Class III and age of the patient, the therapy may be orthopedic and orthodontic surgical orthodontics. The objective was to review the literature of the last 10 years about ways to compensatory treatment of Class III malocclusion. Several articles were published between 04/2003 and 04/2013 in the Pubmed database from the keyword "Class III malocclusion". However, only 19 articles that addressed the compensatory treatment of Class III were selected. Based on the selected items it was concluded that the treatment of Class III malocclusions in children before the peak of pubertal growth has better prognosis with greater effects orthopedic and orthodontic minor effects. The ideal treatment option for this condition is the Rapid maxillary expansion associated with maxillary protraction of the same. The treatment of Class III malocclusion in young people after the peak of pubertal growth is doubtful prognosis. You can opt to treat rapid maxillary expansion and maxillary protraction of the same or fixed appliance, however, orthopedic effects can be the same or smaller than the orthodontic effects, depending on the age of the patient. Depending on the degree of Class III malocclusion in adults, the treatment will consist of dental compensations or orthognathic surgery.

COMPARAÇÃO DE MEDIDAS CEFALOMÉTRICAS DOS ESPAÇOS AÉREOS NASO E OROFARÍNGEO ENTRE RESPIRADORES NASAIS E ORAIS

A literatura tem evidenciado que o modo respiratório alterado influencia nos aspectos estruturais e funcionais do sistema estomatognático. Objetivo: Comparar as medidas cefalométricas dos espaços aéreos naso e orofaríngeo entre respiradores nasais e com modo respiratório alterado (orais ou oronasais). Método: Este estudo de caráter exploratório e retrospectivo utilizou os prontuários de pacientes atendidos na Clínica de Ortodontia, compreendendo o período de 2000 a 2009, sendo que dos 87 indivíduos (má oclusão Classe I de Angle) que compuseram a amostra, 55 eram respiradores nasais (RN) e 32 apresentavam modo respiratório alterado (RON - oronasal ou oral), 47 pertenciam ao sexo feminino e 40 ao masculino, com idades entre 8,75 e 22 anos (média de 14,78 anos). Foram analisadas as telerradiografias em norma lateral, não submetidos a tratamento ortodôntico ou fonoaudiológica prévios. As variáveis de análise foram: idade, sexo, raça, modo respiratório e análise dos espaços naso e orofaringeano pelo método adotado por Zanelato. Por meio de análise estatística (teste t de Student e quiquadrado), os resultados foram interpretados quanto à sua significância. Resultados: Houve diferença estatisticamente significante quanto à idade dos grupos (RN>RON); de prevalência de homens (maior no grupo RON), de leucodermas em ambos os grupos, de via aérea súpero-anterior (menor no grupo RON) e tonsila faríngea (maior no grupo RON); e de tamanho de tonsila faríngea em melanodermas. As demais variáveis de análise não evidenciaram diferenças estatisticamente significantes. Conclusão: As medidas cefalométricas do espaço nasofaringeano (menor no grupo RON) e da tonsila faríngea (maior no grupo RON) diferiram entre os grupos e o espaço orofaringeano não se mostrou diferente entre os grupos. Demais fatores, que não exclusivamente o espaço nasofaríngeo e a tonsila faríngea, podem predispor o indivíduo à respiração oronasal ou predominantemente oral e o ortodontista, em sua rotina clínica, pode avaliar objetivamente as particularidades de cada caso e, desta forma, proceder com condutas adequadas o mais precocemente possível.

Tratamento da má oclusão de Classe II, divisão 1 de Angle, com protrusão maxilar utilizando-se recursos ortopédicos

OBJETIVO: o presente trabalho tem o propósito de apresentar uma revisão da literatura acerca do tratamento da má oclusão de Classe II, divisão 1 de Angle, tendo a protrusão maxilar como o principal componente dessa má oclusão, durante a fase de crescimento e desenvolvimento craniofacial. Serão apresentadas as características de cada um desses aparelhos, os seus componentes, a forma adequada de utilização, os seus mecanismos de ação e, principalmente, os seus efeitos em todo o complexo dentofacial. CONCLUSÃO: nos casos em que se verifica apenas a protrusão maxilar, sem envolvimento mandibular, e se faz necessário o controle vertical, pode ser indicado o AEB, conjugado ao aparelho removível derivado do aparelho preconizado por Thurow. Já nas situações de combinação da protrusão maxilar com a retrusão mandibular, uma opção de tratamento é o ativador combinado à ancoragem extrabucal.

Early cephalometric characteristics in Class III malocclusion

OBJECTIVE: Early identification of craniofacial morphological characteristics allows orthopedic segmented interventions to attenuate dentoskeletal discrepancies, which may be partially disguised by natural dental compensation. To investigate the morphological characteristics of Brazilian children with Class III malocclusion, in stages I and II of cervical vertebrae maturation and compare them with the characteristics of Class I control patients. METHODS: Pre-orthodontic treatment records of 20 patients with Class III malocclusion and 20 control Class I patients, matched by the same skeletal maturity index and sex, were selected. The craniofacial structures and their relationships were divided into different categories for analysis. Angular and linear measures were adopted from the analyses previously described by Downs, Jarabak, Jacobson and McNamara. The differences found between the groups of Class III patients and Class I control group, both subdivided according to the stage of cervical vertebrae maturation (I or II), were assessed by analysis of variance (ANOVA), complemented by Bonferroni's multiple mean comparisons test. RESULTS: The analysis of variance showed statistically significant differences in the different studied groups, between the mean values found for some angular (SNA, SNB, ANB) and linear variables (Co - Gn, N - Perp Pog, Go - Me, Wits, S - Go, Ar - Go). CONCLUSION: Assessed children displaying Class III malocclusion show normal anterior base of skull and maxilla, and anterior positioning of the mandible partially related to increased posterior facial height with consequent mandibular counterclockwise rotation.