The ENIGMA Toolbox: Cross-disorder integration and multiscale neural contextualization of multisite neuroimaging datasets

Abstract

Among ‘big data’ initiatives, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium—a worldwide alliance of over 2,000 scientists diversified into over 50 Working Groups—has yielded some of the largest studies of the healthy and diseased brain. Integration of multisite datasets to assess transdiagnostic similarities and differences and to contextualize findings with respect to neural organization, however, have been limited. Here, we introduce the ENIGMA Toolbox, a Python/Matlab ecosystem for (i) accessing ENIGMA datasets, allowing for cross-disorder analysis, (ii) visualizing data on brain surfaces, and (iii) contextualizing findings at the microscale (postmortem cytoarchitecture and gene expression) and macroscale (structural and functional connectomes). Our Toolbox equips scientists with tutorials to explore molecular, histological, and network correlates of noninvasive neuroimaging markers of brain disorders. Moreover, our Toolbox bridges the gap between standardized data processing protocols and analytic workflows and facilitates cross-consortia initiatives. The Toolbox is documented and openly available at http://enigma-toolbox.readthedocs.io.Abstract Figure

Schizophrenia polygenic risk during typical development reflects multiscale cortical organization

“…We assessed whether PRS-SCZ effects on cortical thickness relate to patterns of cortical thickness abnormalities observed in schizophrenia and other psychiatric illnesses. We made use of recent adult case-control meta-analyses and mega-analysis from the ENIGMA consortium in schizophrenia (van Erp et al ., 2018), bipolar disorder (Hibar et al ., 2018), major depressive disorder (Schmaal et al ., 2017), attention deficit hyperactivity disorder (Hoogman et al ., 2019), obsessive compulsive disorder (Boedhoe et al ., 2017) and autism spectrum disorder (van Rooij et al ., 2018), which are available in our open access ENIGMA toolbox (Lariviere et al ., 2020). To this end, the PRS-SCZ related t-statistic map was parcellated into 64 Desikan-Killiany (DK) atlas regions (Desikan et al ., 2006), and correlated with the case-control Cohen’s d-map for each condition and statistically evaluated relative to 10,000 null models.…”

“…Cortical regions showing PRS-SCZ related greater thickness are those with the strongest thinning across disease maps of schizophrenia and genetically related psychiatric disorders such as bipolar disorder, depression and attention deficits hyperactivity disorder. surfaces show the effect size of schizophrenia, bipolar disorder and major depressive disorder, attention deficit hyperactivity disorder, obsessive compulsive disorder and autism spectrum disorder diagnosis on cortical thickness from mega-analyses of each disorder (Lariviere et al, 2020). Scatterplots show the correlation of each map with PRS-SCZ effect on cortical thickness.…”

Standardizing workflows in imaging transcriptomics with the abagen toolbox

“…We introduce the abagen toolbox, an open-access software package designed to streamline processing and preparation of the AHBA for integration with neuroimaging data , available at https: //github.com/rmarkello/abagen). Supporting several workflows, abagen offers functionality for an array of analyses and has already been used in several peerreviewed publications and preprints (Benkarim et al 2020, Ding et al 2021, Hansen et al 2021, Lariviere et al 2020, Martins et al 2021, 2020, 2020, Valk et al 2021, Zhao et al 2020. The primary workflow, used to generate regional gene expression matrices, integrates 17 distinct processing steps that have previously been employed by research groups throughout the published literature (Table 1).…”

“…Creation of the toolbox has followed best-practices in software development, including version control, continuous integration testing, and modular code design. abagen has already been successfully used in many peer-reviewed publications (Benkarim et al 2020, Ding et al 2021, Hansen et al 2021, Lariviere et al 2020, Martins et al 2021, 2020, 2020, Valk et al 2021, Zhao et al 2020), and we continue to integrate new features as community needs emerge. To encourage further use by new research groups we provide comprehensive documentation on installing and working with the abagen toolbox online (https://abagen.readthedocs.io/).…”

Statistical testing in gene transcriptomic-neuroimaging associations: an evaluation of methods that assess spatial and gene specificity

“…GAMBA complements other tools that link genetics and brain functions, tools such as NeuroSynth (Yarkoni et al, 2011), Brain Annotation Toolbox (Liu et al, 2019), and the ENIGMA toolbox (Larivière et al, 2021) that provide similar platforms to visualize and examine brain maps of gene expression patterns and brain maps, but do not directly provide means to test these effects against multiple null models.…”