GPCRtm : An amino acid substitution matrix for the transmembrane region of class A G Protein-Coupled Receptors

Protein sequence alignments and database search methods use standard scoring matrices calculated from amino acid substitution frequencies in general sets of proteins. These general-purpose matrices are not optimal to align accurately sequences with marked compositional biases, such as hydrophobic transmembrane regions found in membrane proteins. In this work, an amino acid substitution matrix (GPCRtm) is calculated for the membrane spanning segments of the G protein-coupled receptor (GPCR) rhodopsin family; one of the largest transmembrane protein family in humans with great importance in health and disease. The GPCRtm matrix reveals the amino acid compositional bias distinctive of the GPCR rhodopsin family and differs from other standard substitution matrices. These membrane receptors, as expected, are characterized by a high content of hydrophobic residues with regard to globular proteins. On the other hand, the presence of polar and charged residues is higher than in average membrane proteins, displaying high frequencies of replacement within themselves. Analysis of amino acid frequencies and values obtained from the GPCRtm matrix reveals patterns of residue replacements different from other standard substitution matrices. GPCRs prioritize the reactivity properties of the amino acids over their bulkiness in the transmembrane regions. A distinctive role is that charged and polar residues seem to evolve at different rates than other amino acids. This observation is related to the role of the transmembrane bundle in the binding of ligands, that in many cases involve electrostatic and hydrogen bond interactions. This new matrix can be useful in database search and for the construction of more accurate sequence alignments of GPCRs. The online version of this article (doi:10.1186/s12859-015-0639-4) contains supplementary material, which is available to authorized users

Comparison of the web-based and digital questionnaires of the Spanish and Catalan versions of the KIDSCREEN-52

Background: The objectives of the study were to develop web-based Spanish and Catalan versions of the KIDSCREEN, and to compare scores and psychometric properties with the paper version. Methods: Internet and paper Spanish and Catalan versions of the KIDSCREEN-52 were included in a cross-sectional study in school-age children. Web-based and paper Spanish or Catalan versions of the KIDSCREEN-52 were administered to students aged 8 to 18 years from primary and secondary schools in Palafolls (Barcelona, Spain, n5923). All students completed both web-based and paper versions during school time with an interval of at least 2 hours between administrations. The order of administration was randomized. The KIDSCREEN-52, the Strengths and Difficulties Questionnaire (SDQ), and sociodemographic variables were collected. Missing values, floor and ceiling effects, and internal consistency were compared between both versions, as well as mean score differences, level of agreement, and known groups and construct validity. Results: Participation rate was 77% (n5715). Web-based and paper versions showed low percentage of missing values and similar high ceiling effect (range 0 to 44%). Mean score differences showed an effect size (ES) lower than 0.2 in all dimensions. Internal consistency ranged from 0.7 to 0.88, and degree of agreement was excellent (Intraclass correlation coefficient [ICC] range 0.75 to 0.87). Expected differences were seen by sex, age, socioeconomic status and mental health status. Conclusions: The web-based KIDSCREEN-52 showed similar scale score and reliability and validity than the paper version. It will incorporate the child population in the assessment of quality of life providing a more attractive format

Development of the web-based Spanish and Catalan versions of the Euroqol 5D-Y (EQ-5D-Y) and comparison of results with the paper version.

BACKGROUND: The objectives of the study were to develop web-based Spanish and Catalan versions of the EQ-5D-Y, and to compare scores and psychometric properties with the paper version. METHODS: Web-based and paper versions of EQ-5D-Y were included in a cross-sectional study in Palafolls (Barcelona), Spain and administered to students (n = 923) aged 8 to 18 years from 2 primary and 1 secondary school and their parents. All students completed both the web-based and paper versions during school time with an interval of at least 2 h between administrations. The order of administration was randomized. Participants completed EQ-5D-Y, a measure of mental health status (the Strengths and Difficulties Questionnaire), and sociodemographic variables using a self-administered questionnaire. Parents questionnaire included parental level of education and presence of chronic conditions in children. Missing values, and floor and ceiling effects were compared between versions. Mean score differences were computed for the visual analogue scale (VAS). Percentage of agreement, kappa index (k) and intraclass correlation coefficient (ICC) were computed to analyze the level of agreement between web-based and paper versions on EQ-5D-Y dimensions and VAS. Known groups validity was analyzed and compared between the two formats. RESULTS: Participation rate was 77 % (n = 715). Both formats of EQ-5D-Y showed low percentages of missing values (n = 2, and 4 to 9 for web and paper versions respectively), and a high ceiling effect by dimension (range from 79 % to 96 %). Percent agreement for EQ-5D-Y dimensions on the web and paper versions was acceptable (range 89 % to 97 %), and k ranged from 0.55 (0.48-0.61, usual activities dimension) to 0.75 (0.68-0.82, mobility dimension). Mean score difference on the VAS was 0.07, and the ICC for VAS scores on the two formats was 0.84 (0.82-0.86). Both formats showed acceptable ability to discriminate according to self-perceived health, reporting chronic conditions, and mental health status. CONCLUSIONS: The digital EQ-5D-Y showed almost identical VAS scores and acceptable levels of agreement on dimensions. Both formats demonstrated acceptable levels of construct validity. Availability of the Spanish and Catalan web-version will facilitate its use in HRQOL assessment and in economic evaluation.The study was financed by the Spanish Ministry of Health, contract N° PI12/01296

Comparison of scores according to the language (Spanish or Catalan) and order of administration (web or paper first) first (n = 682–713), Palafolls study, 2013.

<p>SD: standard deviation; ES: Standardized mean differences (effect size). Missing values: web version (2); paper version (ranged from n = 7 for BU to n = 30 for the KDS-10 Index). PHY Physical well-being; PSY: Psychological well-being; ME: Moods and emotions; AU: Autonomy: SP: Self-perception; PA: Parent Relation and Home Life; PE: Social Support and Peers; SC: School Environment; BU: Social Acceptance (bullying); FI: Financial Resources.</p><p>Comparison of scores according to the language (Spanish or Catalan) and order of administration (web or paper first) first (n = 682–713), Palafolls study, 2013.</p

Comparison of the web and paper versions of the KIDSCREEN by mental health status according to the Strengths and Difficulties Questionnaire (SDQ, probable case), Palafolls study, 2013 (n = 682–713).

<p>PHY Physical well-being; PSY: Psychological well-being; ME: Moods and emotions; AU: Autonomy: SP: Self-perception; PA: Parent Relation and Home Life; PE: Social Support and Peers; SC: School Environment; BU: Social Acceptance (bullying); FI: Financial Resources; KS-10 Index: KIDSCREEN-10 Index.</p><p>Comparison of the web and paper versions of the KIDSCREEN by mental health status according to the Strengths and Difficulties Questionnaire (SDQ, probable case), Palafolls study, 2013 (n = 682–713).</p

Sociodemographic characteristics of the 713 participants in a comparison of digital and paper versions of the Spanish and Catalan versions of the KIDSCREEN-52.

<p>SD: standard deviation. Missing value: age (2); sex (2); type of family (33); family affluence scale (18); level of education (65); order of administration (2).</p><p>Sociodemographic characteristics of the 713 participants in a comparison of digital and paper versions of the Spanish and Catalan versions of the KIDSCREEN-52.</p

Level of agreement of web and paper versions of the KIDSCREEN-52 (n = 682–713). Palafolls study, 2013.

<p>95%CI: 95% confidence interval; ICC: intraclass correlation coefficient. PHY Physical well-being; PSY: Psychological well-being; ME: Moods and emotions; AU: Autonomy: SP: Self-perception; PA: Parent Relation and Home Life; PE: Social Support and Peers; SC: School Environment; BU: Social Acceptance (bullying); FI: Financial Resources; KS-10 Index: KIDSCREEN-10 Index.</p><p>Level of agreement of web and paper versions of the KIDSCREEN-52 (n = 682–713). Palafolls study, 2013.</p

Comparison of scores, floor and ceiling effect, and internal consistency coefficients between the web and paper versions of the KIDSCREEN (n = 682–713), Palafolls study, 2013.

<p>SD: standard deviation; ES: Standardized mean differences (effect size). Missing values: web version (2); paper version (ranged from n = 7 for BU to n = 30 for the KDS-10 Index). PHY Physical well-being; PSY: Psychological well-being; ME: Moods and emotions; AU: Autonomy: SP: Self-perception; PA: Parent Relation and Home Life; PE: Social Support and Peers; SC: School Environment; BU: Social Acceptance (bullying); FI: Financial Resources; KS-10 Index: KIDSCREEN-10 Index.</p><p>Comparison of scores, floor and ceiling effect, and internal consistency coefficients between the web and paper versions of the KIDSCREEN (n = 682–713), Palafolls study, 2013.</p