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When visualizing a high-dimensional dataset, dimension reduction techniques are commonly employed which provide a single 2 dimensional view of the data. We describe ENS-t-SNE: an algorithm for Embedding Neighborhoods Simultaneously that generalizes the t-Stochastic Neighborhood Embedding approach. By using different viewpoints in ENS-t-SNE’s 3D embedding, one can visualize different types of clusters within the same high-dimensional dataset. This enables the viewer to see and keep track of the different types of clusters, which is harder to do when providing multiple 2D embeddings, where corresponding points cannot be easily identified. We illustrate the utility of ENS-t-SNE with real-world applications and provide an extensive quantitative evaluation with datasets of different types and sizes. 

We present a method for balancing between the Local and Global Structures ( L G S ) in graph embedding, via a tunable parame- ter. Some embedding methods aim to capture global structures, while others attempt to preserve local neighborhoods. Few methods attempt to do both, and it is not always possible to capture well both local and global information in two dimensions, which is where most graph drawing live. The choice of using a local or a global embedding for visualization depends not only on the task but also on the structure of the underly-ing data, which may not be known in advance. For a given graph, L G S aims to find a good balance between the local and global structure to preserve. We evaluate the performance of L G S with synthetic and real- world datasets and our results indicate that it is competitive with the state-of-the-art methods, using established quality metrics such as stress and neighborhood preservation. We introduce a novel quality metric, cluster distance preservation, to assess intermediate structure capture. All source-code, datasets, experiments and analysis are available online. 

Pericentromeric heterochromatin is highly enriched for repetitive sequences prone to aberrant recombination. Previous studies showed that homologous recombination (HR) repair is uniquely regulated in this domain to enable ‘safe’ repair while preventing aberrant recombination. In Drosophila cells, DNA double-strand breaks (DSBs) relocalize to the nuclear periphery through nuclear actin-driven directed motions before recruiting the strand invasion protein Rad51 and completing HR repair. End-joining (EJ) repair also occurs with high frequency in heterochromatin of fly tissues, but how alternative EJ (alt-EJ) pathways operate in heterochromatin remains largely uncharacterized. Here, we induce DSBs in single euchromatic and heterochromatic sites using a new system that combines the DR-white reporter and I-SceI expression in spermatogonia of flies. Using this approach, we detect higher frequency of HR repair in heterochromatin, relative to euchromatin. Further, sequencing of mutagenic repair junctions reveals the preferential use of different EJ pathways across distinct euchromatic and heterochromatic sites. Interestingly, synthesis-dependent microhomology-mediated end joining (SD-MMEJ) appears differentially regulated in the two domains, with a preferential use of motifs close to the cut site in heterochromatin relative to euchromatin, resulting in smaller deletions. Together, these studies establish a new approach to study repair outcomes in fly tissues, and support the conclusion that heterochromatin uses more HR and less mutagenic EJ repair relative to euchromatin. 

The neuroanatomical changes that underpin cognitive development are of major interest in neuroscience. Of the many aspects of neuroanatomy to consider, tertiary sulci are particularly attractive as they emerge last in gestation, show a protracted development after birth, and are either human- or hominoid-specific. Thus, they are ideal targets for exploring morphological-cognitive relationships with cognitive skills that also show protracted development such as working memory (WM). Yet, the relationship between sulcal morphology and WM is unknown—either in development or more generally. To fill this gap, we adopted a data-driven approach with cross-validation to examine the relationship between sulcal depth in lateral prefrontal cortex (LPFC) and verbal WM in 60 children and adolescents between ages 6 and 18. These analyses identified 9 left, and no right, LPFC sulci (of which 7 were tertiary) whose depth predicted verbal WM performance above and beyond the effect of age. Most of these sulci are located within and around contours of previously proposed functional parcellations of LPFC. This sulcal depth model outperformed models with age or cortical thickness. Together, these findings build empirical support for a classic theory that tertiary sulci serve as landmarks in association cortices that contribute to late-maturing human cognitive abilities.

 

A previously uncharted brain structure links functional and anatomical organization and differs across the life span and species.