Automated analysis of whole brain vasculature using machine learning, bioRxiv, 2019-04-19
SUMMARYTissue clearing methods enable imaging of intact biological specimens without sectioning. However, reliable and scalable analysis of such large imaging data in 3D remains a challenge. Towards this goal, we developed a deep learning-based framework to quantify and analyze the brain vasculature, named Vessel Segmentation & Analysis Pipeline (VesSAP). Our pipeline uses a fully convolutional network with a transfer learning approach for segmentation. We systematically analyzed vascular features of the whole brains including their length, bifurcation points and radius at the micrometer scale by registering them to the Allen mouse brain atlas. We reported the first evidence of secondary intracranial collateral vascularization in CD1-Elite mice and found reduced vascularization in the brainstem as compared to the cerebrum. VesSAP thus enables unbiased and scalable quantifications for the angioarchitecture of the cleared intact mouse brain and yields new biological insights related to the vascular brain function.GRAPHICAL ABSTRACT<jatsfig id=ufig1 position=float fig-type=figure orientation=portrait>Supporting material of VesSAP is available at <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpDISCOtechnologies.orgVesSAP>httpDISCOtechnologies.orgVesSAP<jatsext-link><jatsgraphic xmlnsxlink=httpwww.w3.org1999xlink xlinkhref=613257_ufig1 position=float orientation=portrait >
biorxiv neuroscience 200-500-users 2019Diversity begets diversity in microbiomes, bioRxiv, 2019-04-19
AbstractMicrobes are embedded in complex microbiomes where they engage in a wide array of inter- and intra-specific interactions1–4. However, whether these interactions are a significant driver of natural biodiversity is not well understood. Two contrasting hypotheses have been put forward to explain how species interactions could influence diversification. ‘Ecological Controls’ (EC) predicts a negative diversity-diversification relationship, where the evolution of novel types becomes constrained as available niches become filled5. In contrast, ‘Diversity Begets Diversity’ (DBD) predicts a positive relationship, with diversity promoting diversification via niche construction and other species interactions6. Using the Earth Microbiome Project, the largest standardized survey of global biodiversity to date7, we provide support for DBD as the dominant driver of microbiome diversity. Only in the most diverse microbiomes does DBD reach a plateau, consistent with increasingly saturated niche space. Genera that are strongly associated with a particular biome show a stronger DBD relationship than non-residents, consistent with prolonged evolutionary interactions driving diversification. Genera with larger genomes also experience a stronger DBD response, which could be due to a higher potential for metabolic interactions and niche construction offered by more diverse gene repertoires. Our results demonstrate that the rate at which microbiomes accumulate diversity is crucially dependent on resident diversity. This fits a scenario in which species interactions are important drivers of microbiome diversity. Further (population genomic or metagenomic) data are needed to elucidate the nature of these biotic interactions in order to more fully inform predictive models of biodiversity and ecosystem stability4,5.
biorxiv evolutionary-biology 100-200-users 2019GWAS of brain volume on 54,407 individuals and cross-trait analysis with intelligence identifies shared genomic loci and genes, bioRxiv, 2019-04-19
AbstractThe phenotypic correlation between human intelligence and brain volume (BV) is considerable (r≈0.40), and has been shown to be due to shared genetic factors1. To further examine specific genetic factors driving this correlation, we present genomic analyses of the genetic overlap between intelligence and BV using genome-wide association study (GWAS) results. First, we conducted the largest BV GWAS meta-analysis to date (N=54,407 individuals), followed by functional annotation and gene-mapping. We identified 35 genomic loci (27 novel), implicating 362 genes (346 novel) and 23 biological pathways for BV. Second, we used an existing GWAS for intelligence (N=269,867 individuals2), and estimated the genetic correlation (rg) between BV and intelligence to be 0.23. We show that the rg is driven by physical overlap of GWAS hits in 5 genomic loci. We identified 67 shared genes between BV and intelligence, which are mainly involved in important signaling pathways regulating cell growth. Out of these 67 we prioritized 32 that are most likely to have functional impact. These results provide new information on the genetics of BV and provide biological insight into BV’s shared genetic etiology with intelligence.
biorxiv genetics 100-200-users 2019Nanoscale subcellular architecture revealed by multicolor 3D salvaged fluorescence imaging, bioRxiv, 2019-04-19
AbstractCombining the molecular specificity of fluorescent probes with three-dimensional (3D) imaging at nanoscale resolution is critical for investigating the spatial organization and interactions of cellular organelles and protein complexes. We present a super-resolution light microscope that enables simultaneous multicolor imaging of whole mammalian cells at ~20 nm 3D resolution. We show its power for cell biology research with fluorescence images that resolved the highly convoluted Golgi apparatus and the close contacts between the endoplasmic reticulum and the plasma membrane, structures that have traditionally been the imaging realm of electron microscopy.One Sentence SummaryComplex cellular structures previously only resolved by electron microscopy can now be imaged in multiple colors by 4Pi-SMS.
biorxiv biophysics 0-100-users 2019Shared morphological consequences of global warming in North American migratory birds, bioRxiv, 2019-04-19
ABSTRACTIncreasing temperatures associated with climate change are predicted to cause reductions in body size, a key determinant of animal physiology and ecology. Using a four-decade specimen series of 70,716 individuals of 52 North American migratory bird species, we demonstrate that increasing annual summer temperature over the 40-year period drove consistent reductions in body size across these diverse taxa. Concurrently, wing length – which impacts nearly all aspects of avian ecology and behavior – has consistently increased across taxa. Our findings suggest that warming-induced body size reduction is a general response to climate change, and reveal a similarly consistent shift in an ecologically-important dimension of body shape. We hypothesize that increasing wing length represents a compensatory adaptation to maintain migration as reductions in body size have increased the metabolic cost of flight. An improved understanding of warming-induced morphological changes, and their limits, are important for predicting biotic responses to global change.
biorxiv ecology 200-500-users 2019Single Cortical Neurons as Deep Artificial Neural Networks, bioRxiv, 2019-04-19
AbstractWe propose a novel approach based on modern deep artificial neural networks (DNNs) for understanding how the morpho-electrical complexity of neurons shapes their inputoutput (IO) properties at the millisecond resolution in response to massive synaptic input. The IO of integrate and fire point neuron is accurately captured by a DNN with a single unit and one hidden layer. A fully connected DNN with one hidden layer faithfully replicated the IO relationship of a detailed model of Layer 5 cortical pyramidal cell (L5PC) receiving AMPA and GABAA synapses. However, when adding voltage-gated NMDA-conductances, a temporally-convolutional DNN with seven layers was required. Analysis of the DNN filters provides new insights into dendritic processing shaping the IO properties of neurons. This work proposes a systematic approach for characterizing the functional “depth” of a biological neurons, suggesting that cortical pyramidal neurons and the networks they form are computationally much more powerful than previously assumed.
biorxiv neuroscience 500+-users 2019