Adelaide Freitas

Large Scale Comparative Codon-Pair Context Analysis Unveils General Rules that Fine-Tune Evolution of mRNA Primary Structure

Background Codon usage and codon-pair context are important gene primary structure features that influence mRNA decoding fidelity. In order to identify general rules that shape codon-pair context and minimize mRNA decoding error, we have carried out a large scale comparative codon-pair context analysis of 119 fully sequenced genomes. Methodologies/Principal Findings We have developed mathematical and software tools for large scale comparative codon-pair context analysis. These methodologies unveiled general and species specific codon-pair context rules that govern evolution of mRNAs in the 3 domains of life. We show that evolution of bacterial and archeal mRNA primary structure is mainly dependent on constraints imposed by the translational machinery, while in eukaryotes DNA methylation and tri-nucleotide repeats impose strong biases on codon-pair context. Conclusions The data highlight fundamental differences between prokaryotic and eukaryotic mRNA decoding rules, which are partially independent of codon usage.

Comparative context analysis of codon pairs on an ORFeome scale

Codon context is an important feature of gene primary structure that modulates mRNA decoding accuracy. We have developed an analytical software package and a graphical interface for comparative codon context analysis of all the open reading frames in a genome (the ORFeome). Using the complete ORFeome sequences of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Escherichia coli, we show that this methodology permits large-scale codon context comparisons and provides new insight on the rules that govern the evolution of codon-pair context.

Species-Specific Codon Context Rules Unveil Non-Neutrality Effects of Synonymous Mutations

Background Codon pair usage (codon context) is a species specific gene primary structure feature whose evolutionary and functional roles are poorly understood. The data available show that codon-context has direct impact on both translation accuracy and efficiency, but one does not yet understand how it affects these two translation variables or whether context biases shape gene evolution. Methodologies/Principal Findings Here we study codon-context biases using a set of 72 orthologous highly conserved genes from bacteria, archaea, fungi and high eukaryotes to identify 7 distinct groups of codon context rules. We show that synonymous mutations, i.e., neutral mutations that occur in synonymous codons of codon-pairs, are selected to maintain context biases and that non-synonymous mutations, i.e., non-neutral mutations that alter protein amino acid sequences, are also under selective pressure to preserve codon-context biases. Conclusions Since in vivo studies provide evidence for a role of codon context on decoding fidelity in E. coli and for decoding efficiency in mammalian cells, our data support the hypothesis that, like codon usage, codon context modulates the evolution of gene primary structure and fine tunes the structure of open reading frames for high genome translational fidelity and efficiency in the 3 domains of life.

Effect of Background Correction on Cancer Classification with Gene Expression Data

This paper empirically compares six background correction methods aimed at removing unspecific background noise of the overall signal level measured by a scanner across microarrays. Using three published cDNA microarray datasets we investigated the effect of background correction on cancer classification in terms of the predictive performance of two classifiers (k-NN and support vector machine with linear kernel) induced from microarray data where a particular background correction method is applied, individually and in combination with a single-bias or double-bias-removal normalization method.

Computational and Statistical Methodologies for ORFeome Primary Structure Analysis

Codon usage and context are biased in open reading frames (ORFs) of most genomes. Codon usage is largely influenced by biased genome G+C pressure, in particular in prokaryotes, but the general rules that govern the evolution of codon context remain largely elusive. To shed new light into this question, we have developed computational, statistical, and graphical tools for analysis of codon context on an ORFeome wide scale. Here, we describe these methodologies in detail and show how they can be used for analysis of ORFs of any genome sequenced.

The Alternating Least-Squares Algorithm for CDPCA

Clustering and Disjoint Principal Component Analysis (CDPCA) is a constrained principal component analysis recently proposed for clustering of objects and partitioning of variables, simultaneously, which we have implemented in R language. In this paper, we deal in detail with the alternating least-squares algorithm for CDPCA and highlight its algebraic features for constructing both interpretable principal components and clusters of objects. Two applications are given to illustrate the capabilities of this new methodology.

Approximate confidence intervals for a linear combination of binomial proportions: A new variant

ABSTRACT We propose a new adjustment for constructing an improved version of the Wald interval for linear combinations of binomial proportions, which addresses the presence of extremal samples. A comparative simulation study was carried out to investigate the performance of this new variant with respect to the exact coverage probability, expected interval length, and mesial and distal noncoverage probabilities. Additionally, we discuss the application of a criterion for interpreting interval location in the case of small samples and/or in situations in which extremal observations exist. The confidence intervals obtained from the new variant performed better for some evaluation measures.

Disparate faculty perspectives on system changes in higher education

ABSTRACT Higher education (HE) systems around the world have experienced profound structural changes, particularly since the late 1960s to early 1970s, essentially driven by the need to expand access to tertiary education. This has resulted in a diversity of HE institutions (HEI) with different roles, missions and statuses, as well as academic staff with diverse perspectives and motivations. The present study is based on a survey undertaken in Portugal by a trade union, which aimed to collect faculty perspectives on a proposed HE reform sent out for public discussion by the government. Questions addressed the reorganization of the HEI network, the internal restructuring of HEI, the funding system and the binary divide of HEI (universities and polytechnics). The survey results showed a disparity of faculty perspectives about the proposed reform, closely related to the diversity of HEI. Respondents from lower academic categories and from smaller HEI were more opposed to reorganizing the HEI network. This reorganization was more widely accepted by university staff, who were also more in favour of a binary system than were polytechnic respondents. Although there was general agreement about the need to change the funding system, polytechnic respondents were strongly against a funding differentiation between universities and polytechnics. Despite an overall reformist trend, the enthusiasm for reforms declined substantially when the questions had a direct reference to the respondent’s region or institution. It is argued that HE expansion has driven the diversification of HEI, leading to a range of perspectives about the HE system and the way it should be changed. These conclusions may contribute to insights into other HE systems around the world where institutional diversification has been sought by public policies.

Competições em ciência usando tecnologia: um caso de estudo do comportamento das escolas participantes em Portugal

EnglishIn this work we investigate the dynamics of 143 schools of the 3rd cycle of Basic Education in Portugal, regarding the preparation and participation in online science competitions on curricular contents of Mathematics, Portuguese, Physics and Chemistry and Geology. An exploratory factorial analysis of empirical data concerning the competitions in 2015 was carried out, to analyze the characteristics inherent to schools’ performance. Four latent factors describing the schools’ behavior were identified: Quantitative Training, Qualitative Training, Proficiency and Users, which allowed us to verify that: (i) participation in mathematics competition is predominant; (ii) schools participating in two or three competitions present different preparation dynamics; (iii) schools involved only in Mathematics and Physics and Chemistry competitions seem to adopt a more articulated and efficient pedagogical strategy. Although all schools develop a preparatory work before competitions, the strategies used seem to be related to the combination of distinct disciplinary groups participating in the competitions. portuguesNeste trabalho investiga-se a dinâmica de escolas do 3o ciclo do Ensino Basico em Portugal, na preparacao e participacao em uma competicao desenvolvida em ambiente computacional sobre conteudos curriculares de Matematica, Portugues, Fisico-Quimica e Geologia. Foi realizada uma analise fatorial exploratoria de dados empiricos relativos as 143 escolas participantes nas competicoes realizadas em 2015, analisando-se as suas carateristicas de atuacao. Foram identificados quatro fatores latentes descrevendo o comportamento das escolas: Treino quantitativo, Treino qualitativo, Prestacao e Utilizadores, constatando-se que: (i) a participacao na competicao de Matematica e predominante; (ii) escolas participantes em duas ou tres competicoes apresentam diferentes dinâmicas de preparacao; (iii) escolas que participam apenas em Matematica e Fisico-Quimica parecem adotar estrategias pedagogicas mais articuladas e eficientes. Reconhece-se que, embora as escolas participantes desenvolvam trabalhos de preparacao, existe uma tendencia para as escolas apresentarem estrategias distintas de atuacao consoante a combinacao de grupos disciplinares presentes nas competicoes oficiais.

A simple graphical way of evaluating coverage and directional non-coverages

Evaluation of the coverage probability and, more recently, of the intervalar location of confidence intervals, is a useful procedure if exact and asymptotic methods for constructing confidence intervals are used for some populacional parameter. In this paper, a simple graphical procedure is presented to execute this kind of evaluation in confidence methods for linear combinations of k independent binomial proportions. Our proposal is based on the representation of the mesial and distal non-coverage probabilities on a plane. We carry out a simulation study to show how this graphical representation can be interpreted and used as a basis for the evaluation of intervalar location of confidence interval methods.