Studying phenotypic evolution using multivariate quantitative genetics

Quantitative genetics provides a powerful framework for studying phenotypic evolution and the evolution of adaptive genetic variation. Central to the approach is G, the matrix of additive genetic variances and covariances. G summarizes the genetic basis of the traits and can be used to predict the phenotypic response to multivariate selection or to drift. Recent analytical and computational advances have improved both the power and the accessibility of the necessary multivariate statistics. It is now possible to study the relationships between G and other evolutionary parameters, such as those describing the mutational input, the shape and orientation of the adaptive landscape, and the phenotypic divergence among populations. At the same time, we are moving towards a greater understanding of how the genetic variation summarized by G evolves. Computer simulations of the evolution of G, innovations in matrix comparison methods, and rapid development of powerful molecular genetic tools have all opened the way for dissecting the interaction between allelic variation and evolutionary process. Here I discuss some current uses of G, problems with the application of these approaches, and identify avenues for future research.

Predicting class I major histocompatibility complex (MHC) binders using multivariate statistics:comparison of discriminant analysis and multiple linear regression

The accurate in silico identification of T-cell epitopes is a critical step in the development of peptide-based vaccines, reagents, and diagnostics. It has a direct impact on the success of subsequent experimental work. Epitopes arise as a consequence of complex proteolytic processing within the cell. Prior to being recognized by T cells, an epitope is presented on the cell surface as a complex with a major histocompatibility complex (MHC) protein. A prerequisite therefore for T-cell recognition is that an epitope is also a good MHC binder. Thus, T-cell epitope prediction overlaps strongly with the prediction of MHC binding. In the present study, we compare discriminant analysis and multiple linear regression as algorithmic engines for the definition of quantitative matrices for binding affinity prediction. We apply these methods to peptides which bind the well-studied human MHC allele HLA-A*0201. A matrix which results from combining results of the two methods proved powerfully predictive under cross-validation. The new matrix was also tested on an external set of 160 binders to HLA-A*0201; it was able to recognize 135 (84%) of them.

Z2-Graded Polynomial Identities for Superalgebras of Block-Triangular Matrices

000 Mathematics Subject Classification: Primary 16R50, Secondary 16W55.

Involution Matrix Algebras – Identities and Growth

2000 Mathematics Subject Classification: 16R50, 16R10.

Sturm Sequences and Modified Subresultant Polynomial Remainder Sequences

ACM Computing Classification System (1998): F.2.1, G.1.5, I.1.2.

Three New Methods for Computing Subresultant Polynomial Remainder Sequences (PRS’S)

Given the polynomials f, g ∈ Z[x] of degrees n, m, respectively, with n > m, three new, and easy to understand methods — along with the more efficient variants of the last two of them — are presented for the computation of their subresultant polynomial remainder sequence (prs). All three methods evaluate a single determinant (subresultant) of an appropriate sub-matrix of sylvester1, Sylvester’s widely known and used matrix of 1840 of dimension (m + n) × (m + n), in order to compute the correct sign of each polynomial in the sequence and — except for the second method — to force its coefficients to become subresultants. Of interest is the fact that only the first method uses pseudo remainders. The second method uses regular remainders and performs operations in Q[x], whereas the third one triangularizes sylvester2, Sylvester’s little known and hardly ever used matrix of 1853 of dimension 2n × 2n. All methods mentioned in this paper (along with their supporting functions) have been implemented in Sympy and can be downloaded from the link http://inf-server.inf.uth.gr/~akritas/publications/subresultants.py

Test for Independence of the Variables with Missing Elements in One and the Same Column of the Empirical Correlation Matrix

2000 Mathematics Subject Classification: 62H15, 62H12.

Comparative study of dissolved organic matter from groundwater and surface water in the Florida coastal Everglades using multi-dimensional spectrofluorometry combined with multivariate statistics

Dissolved organic matter (DOM) in groundwater and surface water samples from the Florida coastal Everglades were studied using excitation–emission matrix fluorescence modeled through parallel factor analysis (EEM-PARAFAC). DOM in both surface and groundwater from the eastern Everglades S332 basin reflected a terrestrial-derived fingerprint through dominantly higher abundances of humic-like PARAFAC components. In contrast, surface water DOM from northeastern Florida Bay featured a microbial-derived DOM signature based on the higher abundance of microbial humic-like and protein-like components consistent with its marine source. Surprisingly, groundwater DOM from northeastern Florida Bay reflected a terrestrial-derived source except for samples from central Florida Bay well, which mirrored a combination of terrestrial and marine end-member origin. Furthermore, surface water and groundwater displayed effects of different degradation pathways such as photodegradation and biodegradation as exemplified by two PARAFAC components seemingly indicative of such degradation processes. Finally, Principal Component Analysis of the EEM-PARAFAC data was able to distinguish and classify most of the samples according to DOM origins and degradation processes experienced, except for a small overlap of S332 surface water and groundwater, implying rather active surface-to-ground water interaction in some sites particularly during the rainy season. This study highlights that EEM-PARAFAC could be used successfully to trace and differentiate DOM from diverse sources across both horizontal and vertical flow profiles, and as such could be a convenient and useful tool for the better understanding of hydrological interactions and carbon biogeochemical cycling.

Realized Matrix-Exponential Stochastic Volatility with Asymmetry, Long Memory and Spillovers

The paper develops a novel realized matrix-exponential stochastic volatility model of multivariate returns and realized covariances that incorporates asymmetry and long memory (hereafter the RMESV-ALM model). The matrix exponential transformation guarantees the positivedefiniteness of the dynamic covariance matrix. The contribution of the paper ties in with Robert Basmann’s seminal work in terms of the estimation of highly non-linear model specifications (“Causality tests and observationally equivalent representations of econometric models”, Journal of Econometrics, 1988, 39(1-2), 69–104), especially for developing tests for leverage and spillover effects in the covariance dynamics. Efficient importance sampling is used to maximize the likelihood function of RMESV-ALM, and the finite sample properties of the quasi-maximum likelihood estimator of the parameters are analysed. Using high frequency data for three US financial assets, the new model is estimated and evaluated. The forecasting performance of the new model is compared with a novel dynamic realized matrix-exponential conditional covariance model. The volatility and co-volatility spillovers are examined via the news impact curves and the impulse response functions from returns to volatility and co-volatility.

Multivariate Techniques in Biomechanical Analysis

This work outlines the theoretical advantages of multivariate methods in biomechanical data, validates the proposed methods and outlines new clinical findings relating to knee osteoarthritis that were made possible by this approach. New techniques were based on existing multivariate approaches, Partial Least Squares (PLS) and Non-negative Matrix Factorization (NMF) and validated using existing data sets. The new techniques developed, PCA-PLS-LDA (Principal Component Analysis – Partial Least Squares – Linear Discriminant Analysis), PCA-PLS-MLR (Principal Component Analysis – Partial Least Squares –Multiple Linear Regression) and Waveform Similarity (based on NMF) were developed to address the challenging characteristics of biomechanical data, variability and correlation. As a result, these new structure-seeking technique revealed new clinical findings. The first new clinical finding relates to the relationship between pain, radiographic severity and mechanics. Simultaneous analysis of pain and radiographic severity outcomes, a first in biomechanics, revealed that the knee adduction moment’s relationship to radiographic features is mediated by pain in subjects with moderate osteoarthritis. The second clinical finding was quantifying the importance of neuromuscular patterns in brace effectiveness for patients with knee osteoarthritis. I found that brace effectiveness was more related to the patient’s unbraced neuromuscular patterns than it was to mechanics, and that these neuromuscular patterns were more complicated than simply increased overall muscle activity, as previously thought.

Clustering in non-parametric multivariate analyses.

Non-parametric multivariate analyses of complex ecological datasets are widely used. Following appropriate pre-treatment of the data inter-sample resemblances are calculated using appropriate measures. Ordination and clustering derived from these resemblances are used to visualise relationships among samples (or variables). Hierarchical agglomerative clustering with group-average (UPGMA) linkage is often the clustering method chosen. Using an example dataset of zooplankton densities from the Bristol Channel and Severn Estuary, UK, a range of existing and new clustering methods are applied and the results compared. Although the examples focus on analysis of samples, the methods may also be applied to species analysis. Dendrograms derived by hierarchical clustering are compared using cophenetic correlations, which are also used to determine optimum  in flexible beta clustering. A plot of cophenetic correlation against original dissimilarities reveals that a tree may be a poor representation of the full multivariate information. UNCTREE is an unconstrained binary divisive clustering algorithm in which values of the ANOSIM R statistic are used to determine (binary) splits in the data, to form a dendrogram. A form of flat clustering, k-R clustering, uses a combination of ANOSIM R and Similarity Profiles (SIMPROF) analyses to determine the optimum value of k, the number of groups into which samples should be clustered, and the sample membership of the groups. Robust outcomes from the application of such a range of differing techniques to the same resemblance matrix, as here, result in greater confidence in the validity of a clustering approach.

Clustering in non-parametric multivariate analyses.

Non-parametric multivariate analyses of complex ecological datasets are widely used. Following appropriate pre-treatment of the data inter-sample resemblances are calculated using appropriate measures. Ordination and clustering derived from these resemblances are used to visualise relationships among samples (or variables). Hierarchical agglomerative clustering with group-average (UPGMA) linkage is often the clustering method chosen. Using an example dataset of zooplankton densities from the Bristol Channel and Severn Estuary, UK, a range of existing and new clustering methods are applied and the results compared. Although the examples focus on analysis of samples, the methods may also be applied to species analysis. Dendrograms derived by hierarchical clustering are compared using cophenetic correlations, which are also used to determine optimum  in flexible beta clustering. A plot of cophenetic correlation against original dissimilarities reveals that a tree may be a poor representation of the full multivariate information. UNCTREE is an unconstrained binary divisive clustering algorithm in which values of the ANOSIM R statistic are used to determine (binary) splits in the data, to form a dendrogram. A form of flat clustering, k-R clustering, uses a combination of ANOSIM R and Similarity Profiles (SIMPROF) analyses to determine the optimum value of k, the number of groups into which samples should be clustered, and the sample membership of the groups. Robust outcomes from the application of such a range of differing techniques to the same resemblance matrix, as here, result in greater confidence in the validity of a clustering approach.

Multivariate orthogonal polynomials and integrable systems

Multivariate orthogonal polynomials in D real dimensions are considered from the perspective of the Cholesky factorization of a moment matrix. The approach allows for the construction of corresponding multivariate orthogonal polynomials, associated second kind functions, Jacobi type matrices and associated three term relations and also Christoffel-Darboux formulae. The multivariate orthogonal polynomials, their second kind functions and the corresponding Christoffel-Darboux kernels are shown to be quasi-determinants as well as Schur complements of bordered truncations of the moment matrix; quasi-tau functions are introduced. It is proven that the second kind functions are multivariate Cauchy transforms of the multivariate orthogonal polynomials. Discrete and continuous deformations of the measure lead to Toda type integrable hierarchy, being the corresponding flows described through Lax and Zakharov-Shabat equations; bilinear equations are found. Varying size matrix nonlinear partial difference and differential equations of the 2D Toda lattice type are shown to be solved by matrix coefficients of the multivariate orthogonal polynomials. The discrete flows, which are shown to be connected with a Gauss-Borel factorization of the Jacobi type matrices and its quasi-determinants, lead to expressions for the multivariate orthogonal polynomials and their second kind functions in terms of shifted quasi-tau matrices, which generalize to the multidimensional realm, those that relate the Baker and adjoint Baker functions to ratios of Miwa shifted tau-functions in the 1D scenario. In this context, the multivariate extension of the elementary Darboux transformation is given in terms of quasi-determinants of matrices built up by the evaluation, at a poised set of nodes lying in an appropriate hyperplane in R^D, of the multivariate orthogonal polynomials. The multivariate Christoffel formula for the iteration of m elementary Darboux transformations is given as a quasi-determinant. It is shown, using congruences in the space of semi-infinite matrices, that the discrete and continuous flows are intimately connected and determine nonlinear partial difference-differential equations that involve only one site in the integrable lattice behaving as a Kadomstev-Petviashvili type system. Finally, a brief discussion of measures with a particular linear isometry invariance and some of its consequences for the corresponding multivariate polynomials is given. In particular, it is shown that the Toda times that preserve the invariance condition lay in a secant variety of the Veronese variety of the fixed point set of the linear isometry.