Inception in visual cortex in vivo-silico loops reveal most exciting images, bioRxiv, 2018-12-29
Much of our knowledge about sensory processing in the brain is based on quasi-linear models and the stimuli that optimally drive them. However, sensory information processing is nonlinear, even in primary sensory areas, and optimizing sensory input is difficult due to the high-dimensional input space. We developed inception loops, a closed-loop experimental paradigm that combines in vivo recordings with in silico nonlinear response modeling to identify the Most Exciting Images (MEIs) for neurons in mouse V1. When presented back to the brain, MEIs indeed drove their target cells significantly better than the best stimuli identified by linear models. The MEIs exhibited complex spatial features that deviated from the textbook ideal of V1 as a bank of Gabor filters. Inception loops represent a widely applicable new approach to dissect the neural mechanisms of sensation.
biorxiv neuroscience 0-100-users 2018Plants emit informative airborne sounds under stress, bioRxiv, 2018-12-29
Stressed plants show altered phenotypes, including changes in color, smell, and shape. Yet, the possibility that plants emit airborne sounds when stressed, similarly to many animals, has not been investigated. Here we show, to our knowledge for the first time, that stressed plants emit airborne sounds that can be recorded remotely, both in acoustic chambers and in greenhouses. We recorded ~65 dBSPL ultrasonic sounds 10 cm from tomato and tobacco plants, implying that these sounds could be detected by some organisms from up to several meters away. We developed machine learning models that were capable of distinguishing between plant sounds and general noises, and identifying the condition of the plants dry, cut, or intact, based solely on the emitted sounds. Our results suggest that animals, humans, and possibly even other plants, could use sounds emitted by a plant to gain information about the plant's condition. More investigation on plant bioacoustics in general and on sound emission in plants in particular may open new avenues for understanding plants and their interactions with the environment, and it may also have a significant impact on agriculture.
biorxiv plant-biology 500+-users 2018Neocortical layer 4 in adult mouse differs in major cell types and circuit organization between primary sensory areas, bioRxiv, 2018-12-28
AbstractLayer 4 (L4) of mammalian neocortex plays a crucial role in cortical information processing, yet a complete census of its cell types and connectivity remains elusive. Using whole-cell recordings with morphological recovery, we identified one major excitatory and seven inhibitory types of neurons in L4 of adult mouse visual cortex (V1). Nearly all excitatory neurons were pyramidal and all somatostatin-positive (SOM+) non-fast-spiking neurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory neurons were mostly stellate and SOM+ neurons were non-Martinotti. These morphologically distinct SOM+ interneurons corresponded to different transcriptomic cell types and were differentially integrated into the local circuit with only S1 neurons receiving local excitatory input. We propose that cell-type specific circuit motifs, such as the Martinottipyramidal and non-Martinottistellate pairs, are optionally used across the cortex as building blocks to assemble cortical circuits.
biorxiv neuroscience 100-200-users 2018Single-cell multi-omic profiling of chromatin conformation and DNA methylome, bioRxiv, 2018-12-27
AbstractRecent advances in the development of single cell epigenomic assays have facilitated the analysis of gene regulatory landscapes in complex biological systems. Methods for detection of single-cell epigenomic variation such as DNA methylation sequencing and ATAC-seq hold tremendous promise for delineating distinct cell types and identifying their critical cis-regulatory sequences. Emerging evidence has shown that in addition to cis-regulatory sequences, dynamic regulation of 3D chromatin conformation is a critical mechanism for the modulation of gene expression during development and disease. It remains unclear whether single-cell Chromatin Conformation Capture (3C) or Hi-C profiles are suitable for cell type identification and allow the reconstruction of cell-type specific chromatin conformation maps. To address these challenges, we have developed a multi-omic method single-nucleus methyl-3C sequencing (sn-m3C-seq) to profile chromatin conformation and DNA methylation from the same cell. We have shown that bulk m3C-seq and sn-m3C-seq accurately capture chromatin organization information and robustly separate mouse cell types. We have developed a fluorescent-activated nuclei sorting strategy based on DNA content that eliminates nuclei multiplets caused by crosslinking. The sn-m3C-seq method allows high-resolution cell-type classification using two orthogonal types of epigenomic information and the reconstruction of cell-type specific chromatin conformation maps.
biorxiv genomics 100-200-users 2018The mutational landscape of normal human endometrial epithelium, bioRxiv, 2018-12-24
All normal somatic cells are thought to acquire mutations. However, characterisation of the patterns and consequences of somatic mutation in normal tissues is limited. Uterine endometrium is a dynamic tissue that undergoes cyclical shedding and reconstitution and is lined by a gland-forming epithelium. Whole genome sequencing of normal endometrial glands showed that most are clonal cell populations derived from a recent common ancestor with mutation burdens differing from other normal cell types and manyfold lower than endometrial cancers. Mutational signatures found ubiquitously account for most mutations. Many, in some women potentially all, endometrial glands are colonised by cell clones carrying driver mutations in cancer genes, often with multiple drivers. Total and driver mutation burdens increase with age but are also influenced by other factors including body mass index and parity. Clones with drivers often originate during early decades of life. The somatic mutational landscapes of normal cells differ between cell types and are revealing the procession of neoplastic change leading to cancer.
biorxiv cancer-biology 0-100-users 2018Estimating heritability of complex traits in admixed populations with summary statistics, bioRxiv, 2018-12-21
AbstractAll summary statistics-based methods to estimate the heritability of SNPs (hg2) rely on accurate linkage disequilibrium (LD) calculations. In admixed populations, such as African Americans and Latinos, LD estimates are influenced by admixture and can result in biased hg2 estimates. Here, we introduce covariate-adjusted LD score regression (cov-LDSC), a method to provide robust hg2 estimates from GWAS summary statistics and in-sample LD estimates in admixed populations. In simulations, we observed that unadjusted LDSC underestimates hg2 by 10%-60%; in contrast, cov-LDSC is robust to all simulation parameters. We applied cov-LDSC to approximately 170,000 Latino, 47,000 African American 135,000 European individuals in three quantitative and five dichotomous phenotypes. Our results show that most traits have high concordance of hg2 between ethnic groups; for example in the 23andMe cohort, estimates of hg2 for BMI are 0.22 ± 0.01, 0.23 ± 0.03 and 0.22 ± 0.01 in Latino, African American and European populations respectively. However, for age at menarche, we observe population specific heritability differences with estimates of hg2 of 0.10 ± 0.03, 0.33 ± 0.13 and 0.19 ± 0.01 in Latino, African American and European populations respectively.
biorxiv genetics 100-200-users 2018