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We describe tethered conformation capture (TCC), a method for genome-wide mapping of chromatin interactions. By performing ligations on solid substrates rather than in solution, TCC substantially enhances the signal-to-noise ratio, thereby facilitating a detailed analysis of interactions within and between chromosomes. We identified a group of regions in(More)
Understanding the spatial organization of gene expression with single-nucleotide resolution requires localizing the sequences of expressed RNA transcripts within a cell in situ. Here, we describe fluorescent in situ RNA sequencing (FISSEQ), in which stably cross-linked complementary DNA (cDNA) amplicons are sequenced within a biological sample. Using(More)
Simultaneously measuring the activities of all neurons in a mammalian brain at millisecond resolution is a challenge beyond the limits of existing techniques in neuroscience. Entirely new approaches may be required, motivating an analysis of the fundamental physical constraints on the problem. We outline the physical principles governing brain activity(More)
We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. This analysis suggests potential cost-effective strategies for dense connectivity mapping at the scale of whole mammalian brains.
We propose a neural connectomics strategy called Fluorescent In-Situ Sequencing of Barcoded Individual Neuronal Connections (FISSEQ-BOINC), leveraging fluorescent in situ nucleic acid sequencing in fixed tissue (FISSEQ) [1, 2]. FISSEQ-BOINC exhibits different properties from BOINC [3, 4], which relies on bulk nucleic acid sequencing. FISSEQ-BOINC could(More)
PURPOSE The gene coding cytochrome P4501B1 (CYP1B1) has been shown to be a major cause of primary congenital glaucoma in the Iranian population. More recently it was shown to also be important in juvenile-onset open angle glaucoma (JOAG). We aimed to further investigate the role of CYP1B1 in a larger cohort of primary open angle glaucoma (POAG) patients(More)
PURPOSE To perform a mutation screening of TACSTD2 in 13 Iranian Gelatinous Drop-like Corneal Dystrophy (GDLD) pedigrees. To assess genotype-phenotype correlations. To determine intragenic SNP haplotypes associated with the mutations, so as to gain information on their origin. METHODS The coding region of TACSTD2 was sequenced in the probands of 13(More)
Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic(More)
We analyze the scaling and cost-performance characteristics of current and projected connectomics approaches, with reference to the potential implications of recent advances in diverse contributing fields. Three generalized strategies for dense connectivity mapping at the scale of whole mammalian brains are considered: electron microscopic axon tracing,(More)
​ We present here an approach for engineering evolving DNA barcodes in living cells. The methodology entails use of a homing guide RNA (hgRNA) scaffold that directs the Cas9­hgRNA complex to target the DNA locus of the hgRNA itself. We show this homing CRISPR­Cas9 system acts as an expressed evolving genetic barcode, and corresponding small RNAs can be(More)