Summary: Parallel heatmaps with carefully designed annotation graphics are powerful for efficient visualization of patterns and relationships among high dimensional genomic data. Here we present the ComplexHeatmap package that provides rich functionalities for customizing heatmaps, arranging multiple parallel heatmaps and including user-defined annotation graphics. We demonstrate the power of ComplexHeatmap to easily reveal patterns and correlations among multiple sources of information with four real-world datasets. Availability and Implementation: The ComplexHeatmap package and documentation are freely available from the Bioconductor project: http://www.bioconductor.org/packages/devel/bioc/html/ComplexHeatmap.html. Contact: m.schlesner@dkfz.de Supplementary information: Supplementary data are available at Bioinformatics online.

/pdf/complex-heatmaps-reveal-patterns-and-correlations-in-5o9nvr4wa3.pdf

Complex heatmaps reveal patterns and correlations in multidimensional genomic data

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Table Of Integrals Series And Products

The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. We define 133 transcriptomic cell types by deep, single-cell RNA sequencing. Nearly all types of GABA (γ-aminobutyric acid)-containing neurons are shared across both areas, whereas most types of glutamatergic neurons were found in one of the two areas. By combining single-cell RNA sequencing and retrograde labelling, we match transcriptomic types of glutamatergic neurons to their long-range projection specificity. Our study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct areas of the adult mouse cortex.

/pdf/shared-and-distinct-transcriptomic-cell-types-across-93yl5rzpm7.pdf

Shared and distinct transcriptomic cell types across neocortical areas

Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumor, allowing for discrimination between different tumor tissues and subtypes, even after long-term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumorogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug-screening testing and led to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease.

/pdf/human-primary-liver-cancer-derived-organoid-cultures-for-cbieemhnh7.pdf

Human primary liver cancer–derived organoid cultures for disease modeling and drug screening

Intellectual abilities in Alzheimer's disease patients: Contributions from the Wechsler Abbreviated Scale of Intelligence (WASI)

Summary: dendextend is an R package for creating and comparing visually appealing tree diagrams. dendextend provides utility functions for manipulating dendrogram objects (their color, shape and content) as well as several advanced methods for comparing trees to one another (both statistically and visually). As such, dendextend offers a flexible framework for enhancing R's rich ecosystem of packages for performing hierarchical clustering of items.

Availability and implementation: The dendextend R package (including detailed introductory vignettes) is available under the GPL-2 Open Source license and is freely available to download from CRAN at: (http://cran.r-project.org/package=dendextend)

Contact: li.ca.uat.htam@ililaG.laT

dendextend: an R package for visualizing, adjusting and comparing trees of hierarchical clustering

Summary heatmaply is an R package for easily creating interactive cluster heatmaps that can be shared online as a stand-alone HTML file. Interactivity includes a tooltip display of values when hovering over cells, as well as the ability to zoom in to specific sections of the figure from the data matrix, the side dendrograms, or annotated labels. Thanks to the synergistic relationship between heatmaply and other R packages, the user is empowered by a refined control over the statistical and visual aspects of the heatmap layout. Availability and implementation The heatmaply package is available under the GPL-2 Open Source license. It comes with a detailed vignette, and is freely available from: http://cran.r-project.org/package=heatmaply. Contact tal.galili@math.tau.ac.il. Supplementary information Supplementary data are available at Bioinformatics online.

/pdf/heatmaply-an-r-package-for-creating-interactive-cluster-5ghvzq1bgc.pdf

heatmaply: an R package for creating interactive cluster heatmaps for online publishing.

The Proprioceptive System Masterminds Spinal Alignment: Insight into the Mechanism of Scoliosis

To obtain a perspective on an animal's own functional world, we study its behavior in situations that allow the animal to regulate the growth rate of its behavior and provide us with the opportunity to quantify its moment-by-moment developmental dynamics. Thus, we are able to show that mouse exploratory behavior consists of sequences of repeated motion: iterative processes that increase in extent and complexity, whose presumed function is a systematic active management of input acquired during the exploration of a novel environment. We use this study to demonstrate our approach to quantifying behavior: targeting aspects of behavior that are shown to be actively managed by the animal, and using measures that are discriminative across strains and treatments and replicable across laboratories.

https://www.pnas.org/content/pnas/108/Supplement_3/15580.full.pdf

Quantifying the buildup in extent and complexity of free exploration in mice

BACKGROUND AND AIMS Although smoking cessation medications have shown effectiveness in increasing abstinence in randomized controlled trials (RCTs), it is unclear to what extent benefits persist over time. This paper assesses whether the benefits of smoking cessation medications decline over the first year. METHODS We selected studies from three systematic reviews published by the Cochrane Collaboration. RCTs of first-line smoking cessation medications, with 6- and 12-month follow-up, were eligible for inclusion. Meta-analysis was used to synthesize information on sustained abstinence (SA) at 6 versus 12 months and 3 versus 6 months, using the risk difference (RD) ('net benefit') between intervention and control group quit rates, the relative risk (RR) and the odds ratio (OR). RESULTS Sixty-one studies (27 647 participants) were included. Fewer than 40% of intervention group participants were sustained abstinent at 3 months (bupropion: 37.1%; nicotine replacement therapy (NRT): 34.8%; varenicline: 39.3%); approximately a quarter were sustained abstinent at 6 months (bupropion: 25.9%; NRT: 26.6%; varenicline: 25.4%), and approximately a fifth were sustained abstinent at 12 months (bupropion: 19.9%; NRT: 19.8%%; varenicline: 18.7%). There was only a small decline in RR (3 months: 1.95 [95% confidence interval (CI) = 1.74-2.18, P < 0.0001]; 6 months: 1.87 (95% CI = 1.67-2.08 P < 0.0001); 12 months: 1.75 (95% CI = 1.56-1.95, P < 0.0001) between intervention and control groups over time, but a substantial decline in net benefit [3 months: RD = 17.3% (14.5-20.1%); 6 months: RD = 11.8% (10.0-13.7%); 12 months: RD = 8.2% (6.8-9.6%)]. The decline in net benefit was statistically significant between 3 and 6 [RD = 4.95% (95% CI = 3.49-6.41%), P < 0.0001] and 6 and 12 months [RD = 3.00% (95% CI = 2.36%-3.64%), P < 0.0001)] for medications combined and individual medications. CONCLUSIONS The proportion of smokers who use smoking cessation medications who benefit from doing so decreases during the course of the first year, but a net benefit still remains at 12 months.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/add.14134

Tal Galili

Papers

dendextend: an R package for visualizing, adjusting and comparing trees of hierarchical clustering

heatmaply: an R package for creating interactive cluster heatmaps for online publishing.

The Proprioceptive System Masterminds Spinal Alignment: Insight into the Mechanism of Scoliosis

Quantifying the buildup in extent and complexity of free exploration in mice

Diminishing benefit of smoking cessation medications during the first year: a meta-analysis of randomized controlled trials