Project description:<p>The Human Connectome Project (HCP) has acquired vast amounts of data about the pattern of long-distance connections (wiring) in the brains of large numbers of healthy participants aged 22-35 using cutting-edge MRI and MEG neuroimaging, and extensive behavioral testing. Types of MR data collected included diffusion MRI (dMRI), resting-state functional MRI (r-fMRI), and structural MRI at both 3T and 7T, and task-evoked functional MRI (t-fMRI) at 3T. </p> <p>Following an extensive period of development and optimization of data acquisition and analysis methods, at Washington University in St. Louis we studied 1,206 participants comprising twins and their non-twin siblings. A subset of 184 twins was scanned again at the University of Minnesota using a 7T scanner. A different subset of 95 twins was studied at St. Louis University using combined resting state and/or task-activated MEG.</p> <p>We were able to collect genetic data on 1142 of our 1206 participants, including 149 pairs of genetically-confirmed monozygotic twins (298 participants) and 94 pairs of genetically-confirmed dizygotic twins (188 participants). Overall, there are 457 different families in the study, as determined by genetic analysis.</p> <p>Our rich set of imaging, behavioral and genetic data - available through the <a href="https://www.humanconnectome.org/data/">Human Connectome</a> database - will enable many types of analysis of brain circuitry, its relationship to behavior, and the contributions of genetic and environmental factors to brain circuits. </p>
Project description:The connectome, a comprehensive map of the brain's anatomical connections, is often summarized as a matrix comprising all dyadic connections among pairs of brain regions. This representation cannot capture higher-order relations within the brain graph. Connectome embedding (CE) addresses this limitation by creating compact vectorized representations of brain nodes capturing their context in the global network topology. Here, nodes "context" is defined as random walks on the brain graph and as such, represents a generative model of diffusive communication around nodes. Applied to group-averaged structural connectivity, CE was previously shown to capture relations between inter-hemispheric homologous brain regions and uncover putative missing edges from the network reconstruction. Here we extend this framework to explore individual differences with a novel embedding alignment approach. We test this approach in two lifespan datasets (NKI: n = 542; Cam-CAN: n = 601) that include diffusion-weighted imaging, resting-state fMRI, demographics and behavioral measures. We demonstrate that modeling functional connectivity with CE substantially improves structural to functional connectivity mapping both at the group and subject level. Furthermore, age-related differences in this structure-function mapping, are preserved and enhanced. Importantly, CE captures individual differences by out-of-sample prediction of age and intelligence. The resulting predictive accuracy was higher compared to using structural connectivity and functional connectivity. We attribute these findings to the capacity of the CE to incorporate aspects of both anatomy (the structural graph) and function (diffusive communication). Our novel approach allows mapping individual differences in the connectome through structure to function and behavior.
Project description:The long non-coding RNA (lncRNA) Xist is a master regulator of X-chromosome inactivation in mammalian cells. Models for how Xist and other lncRNAs function depend on thermodynamically stable secondary and higher-order structures that RNAs can form in the context of a cell. Probing accessible RNA bases can provide data to build models of RNA conformation that provide insight into RNA function, molecular evolution, and modularity. To study the structure of Xist in cells, we built upon recent advances in RNA secondary structure mapping and modeling to develop Targeted Structure-Seq, which combines chemical probing of RNA structure in cells with target-specific massively parallel sequencing. By enriching for signals from the RNA of interest, Targeted Structure-Seq achieves high coverage of the target RNA with relatively few sequencing reads, thus providing a targeted and scalable approach to analyze RNA conformation in cells. We use this approach to probe the full-length Xist lncRNA to develop new models for functional elements within Xist, including the repeat A element in the 5'-end of Xist. This analysis also identified new structural elements in Xist that are evolutionarily conserved, including a new element proximal to the C repeats that is important for Xist function. Examination of dimethylsufate reactivity of Xist lncRNA and 18S rRNA in cells using targeted reverse transcription to determine reactivity, and comparisons with untreated control samples.
Project description:IntroductionThe functional connectivity patterns in the brain are highly heritable; however, it is unclear how genetic factors influence the directionality of such "information flows." Studying the "directionality" of the brain functional connectivity and assessing how heritability modulates it can improve our understanding of the human connectome.MethodsHere, we investigated the heritability of "directed" functional connections using a state-space formulation of Granger causality (GC), in conjunction with blind deconvolution methods accounting for local variability in the hemodynamic response function. Such GC implementation is ideal to explore the directionality of functional interactions across a large number of networks. Resting-state functional magnetic resonance imaging data were drawn from the Human Connectome Project (total n = 898 participants). To add robustness to our findings, the dataset was randomly split into a "discovery" and a "replication" sample (each with n = 449 participants). The two cohorts were carefully matched in terms of demographic variables and other confounding factors (e.g., education). The effect of shared environment was also modeled.ResultsThe parieto- and prefronto-cerebellar, parieto-prefrontal, and posterior-cingulate to hippocampus connections showed the highest and most replicable heritability effects with little influence by shared environment. In contrast, shared environmental factors significantly affected the visuo-parietal and sensory-motor directed connectivity.ConclusionWe suggest a robust role of heritability in influencing the directed connectivity of some cortico-subcortical circuits implicated in cognition. Further studies, for example using task-based fMRI and GC, are warranted to confirm the asymmetric effects of genetic factors on the functional connectivity within cognitive networks and their role in supporting executive functions and learning.