41. Materials and methods are available as supplementary materials on Science Online. 42. One of the features of our approach is its ability to distinguish between antibodies targeting overlapping epitopes in a substantially different ways: There is a significant difference in the correlation coefficients for antibodies targeting a similar epitope versus the correlation coefficients for antibodies targeting different epitopes on the same site of vulnerability. Similarly, there is a significant difference for similar epitopes versus different sites of vulnerability; however, there is no significant difference for different epitopes on the same site of vulnerability versus different sites of vulnerability (fig. S1). 43. R. M. Cardoso et al., Immunity 22, 163 (2005). 44. Residue numbering throughout the paper is relative to strain HXB2, unless stated otherwise.

Assessing and analysing individual differences in change over time is of central scientific importance to developmental neuroscience. However, the literature is based largely on cross-sectional comparisons, which reflect a variety of influences and cannot directly represent change. We advocate using latent change score (LCS) models in longitudinal samples as a statistical framework to tease apart the complex processes underlying lifespan development in brain and behaviour using longitudinal data. LCS models provide a flexible framework that naturally accommodates key developmental questions as model parameters and can even be used, with some limitations, in cases with only two measurement occasions. We illustrate the use of LCS models with two empirical examples. In a lifespan cognitive training study (COGITO, N = 204 (N = 32 imaging) on two waves) we observe correlated change in brain and behaviour in the context of a high-intensity training intervention. In an adolescent development cohort (NSPN, N = 176, two waves) we find greater variability in cortical thinning in males than in females. To facilitate the adoption of LCS by the developmental community, we provide analysis code that can be adapted by other researchers and basic primers in two freely available SEM software packages (lavaan and Ωnyx).

In the behavioral and social sciences, structural equation models (SEMs) have become widely accepted as a modeling tool for the relation between latent and observed variables. SEMs can be seen as a unification of several multivariate analysis techniques. SEM Trees combine the strengths of SEMs and the decision tree paradigm by building tree structures that separate a data set recursively into subsets with significantly different parameter estimates in a SEM. SEM Trees provide means for finding covariates and covariate interactions that predict differences in structural parameters in observed as well as in latent space and facilitate theory-guided exploration of empirical data. We describe the methodology, discuss theoretical and practical implications, and demonstrate applications to a factor model and a linear growth curve model.

Structural equation model (SEM) trees, a combination of SEMs and decision trees, have been proposed as a data-analytic tool for theory-guided exploration of empirical data. With respect to a hypothesized model of multivariate outcomes, such trees recursively find subgroups with similar patterns of observed data. SEM trees allow for the automatic selection of variables that predict differences across individuals in specific theoretical models, for instance, differences in latent factor profiles or developmental trajectories. However, SEM trees are unstable when small variations in the data can result in different trees. As a remedy, SEM forests, which are ensembles of SEM trees based on resamplings of the original dataset, provide increased stability. Because large forests are less suitable for visual inspection and interpretation, aggregate measures provide researchers with hints on how to improve their models: (a) variable importance is based on random permutations of the out-of-bag (OOB) samples of the individual trees and quantifies, for each variable, the average reduction of uncertainty about the model-predicted distribution; and (b) case proximity enables researchers to perform clustering and outlier detection. We provide an overview of SEM forests and illustrate their utility in the context of cross-sectional factor models of intelligence and episodic memory. We discuss benefits and limitations, and provide advice on how and when to use SEM trees and forests in future research.