@article{ji_griffing_thorne_2016, title={A Phylogenetic Approach Finds Abundant Interlocus Gene Conversion in Yeast}, volume={33}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/msw114}, abstractNote={Interlocus gene conversion (IGC) homogenizes repeats. While genomes can be repeat-rich, the evolutionary importance of IGC is poorly understood. Additional statistical tools for characterizing it are needed. We propose a composite likelihood strategy for incorporating IGC into widely-used probabilistic models for sequence changes that originate with point mutation. We estimated the percentage of nucleotide substitutions that originate with an IGC event rather than a point mutation in 14 groups of yeast ribosomal protein-coding genes, and found values ranging from 20% to 38%. We designed and applied a procedure to determine whether these percentages are inflated due to artifacts arising from model misspecification. The results of this procedure are consistent with IGC having had an important role in the evolution of each of these 14 gene families. We further investigate the properties of our IGC approach via simulation. In contrast to usual practice, our findings suggest that the IGC should and can be considered when multigene family evolution is investigated.}, number={9}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Ji, Xiang and Griffing, Alexander and Thorne, Jeffrey L.}, year={2016}, month={Sep}, pages={2469–2476} }
@article{wang_yu_ji_lakner_griffing_thorne_2015, title={Roles of Solvent Accessibility and Gene Expression in Modeling Protein Sequence Evolution}, volume={11}, ISSN={["1176-9343"]}, DOI={10.4137/ebo.s22911}, abstractNote={Models of protein evolution tend to ignore functional constraints, although structural constraints are sometimes incorporated. Here we propose a probabilistic framework for codon substitution that evaluates joint effects of relative solvent accessibility (RSA), a structural constraint; and gene expression, a functional constraint. First, we explore the relationship between RSA and codon usage at the genomic scale as well as at the individual gene scale. Motivated by these results, we construct our framework by determining how probable is an amino acid, given RSA and gene expression, and then evaluating the relative probability of observing a codon compared to other synonymous codons. We come to the biologically plausible conclusion that both RSA and gene expression are related to amino acid frequencies, but, among synonymous codons, the relative probability of a particular codon is more closely related to gene expression than RSA. To illustrate the potential applications of our framework, we propose a new codon substitution model. Using this model, we obtain estimates of 27 N s, the product of effective population size N, and relative fitness difference of allele s. For a training data set consisting of human proteins with known structures and expression data, 2 N s is estimated separately for synonymous and nonsynonymous substitutions in each protein. We then contrast the patterns of synonymous and nonsynonymous 2 N s estimates across proteins while also taking gene expression levels of the proteins into account. We conclude that our 2 N s estimates are too concentrated around 0, and we discuss potential explanations for this lack of variability.}, journal={EVOLUTIONARY BIOINFORMATICS}, author={Wang, Kuangyu and Yu, Shuhui and Ji, Xiang and Lakner, Clemens and Griffing, Alexander and Thorne, Jeffrey L.}, year={2015} }
@article{griffing_lynch_stone_2014, title={Structural properties of the minimum cut of partially-supplied graphs}, volume={177}, ISSN={["1872-6771"]}, DOI={10.1016/j.dam.2014.05.043}, abstractNote={It is well known that information about the structure of a graph is contained within its minimum cut. Here we investigate how the minimum cut of one graph informs the structure of a second, related graph. We consider pairs of graphs G and H, with respective Laplacian matrices L and M, and call H partially supplied provided that M is a Schur complement of L. Our results show how the minimum cut of H relates to the structure of the larger graph G.}, journal={DISCRETE APPLIED MATHEMATICS}, author={Griffing, Alexander R. and Lynch, Benjamin R. and Stone, Eric A.}, year={2014}, month={Nov}, pages={152–157} }
@article{myers_casals_gauthier_hamdan_keebler_boyko_bustamante_piton_spiegelman_henrion_et al._2011, title={A population genetic approach to mapping neurological disorder genes using deep resequencing}, volume={7}, number={2}, journal={PLoS Genetics}, author={Myers, R. A. and Casals, F. and Gauthier, J. and Hamdan, F. F. and Keebler, J. and Boyko, A. R. and Bustamante, C. D. and Piton, A. M. and Spiegelman, D. and Henrion, E. and et al.}, year={2011} }
@article{awadalla_gauthier_myers_casals_hamdan_griffing_cote_henrion_spiegelman_tarabeux_et al._2010, title={Direct measure of the de novo mutation rate in autism and schizophrenia cohorts}, volume={87}, number={3}, journal={American Journal of Human Genetics}, author={Awadalla, P. and Gauthier, J. and Myers, R. A. and Casals, F. and Hamdan, F. F. and Griffing, A. R. and Cote, M. and Henrion, E. and Spiegelman, D. and Tarabeux, J. and et al.}, year={2010}, pages={316–324} }
@article{stone_griffing_2009, title={On the Fiedler vectors of graphs that arise from trees by Schur complementation of the Laplacian}, volume={431}, ISSN={["0024-3795"]}, DOI={10.1016/j.laa.2009.06.024}, abstractNote={The utility of Fiedler vectors in interrogating the structure of graphs has generated intense interest and motivated the pursuit of further theoretical results. This paper focuses on how the Fiedler vectors of one graph reveal structure in a second graph that is related to the first. Specifically, we consider a point of articulation r in the graph G whose Laplacian matrix is L and derive a related graph G{r} whose Laplacian is the matrix obtained by taking the Schur complement with respect to r in L. We show how Fiedler vectors of G{r} relate to the structure of G and we provide bounds for the algebraic connectivity of G{r} in terms of the connected components at r in G. In the case where G is a tree with points of articulation r ∈ R, we further consider the graph GR derived from G by taking the Schur complement with respect to R in L. We show that Fiedler vectors of GR valuate the pendent vertices of G in a manner consistent with the structure of the tree.}, number={10}, journal={LINEAR ALGEBRA AND ITS APPLICATIONS}, author={Stone, Eric A. and Griffing, Alexander R.}, year={2009}, month={Oct}, pages={1869–1880} }