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Michael Schnall-Levin

Publications and source records attributed to Michael Schnall-Levin.

2 recordsLinked to original sources

Massively parallel digital transcriptional profiling of single cells

Characterizing the transcriptome of individual cells is fundamental to understanding complex biological systems. We describe a droplet-based system that enables 3' mRNA counting of up to tens of thousands of single cells per sample. Cell encapsulation in droplets takes place in [~]6 minutes, with [~]50% cell capture efficiency, up to 8 samples at a time. The speed and efficiency allow the processing of precious samples while minimizing stress to cells. To demonstrate the system's technical performance and its applications, we collected transcriptome data from [~][1/4] million single cells across 29 samples. First, we validate the sensitivity of the system and its ability to detect rare populations using cell lines and synthetic RNAs. Then, we profile 68k peripheral blood mononuclear cells (PBMCs) to demonstrate the system's ability to characterize large immune populations. Finally, we use sequence variation in the transcriptome data to determine host and donor chimerism at single cell resolution in bone marrow mononuclear cells (BMMCs) of transplant patients. This analysis enables characterization of the complex interplay between donor and host cells and monitoring of treatment response. This high-throughput system is robust and enables characterization of diverse biological systems with single cell mRNA analysis.

Genomics

Health and population effects of rare gene knockouts in adult humans with related parents

AbstractComplete gene knockouts are highly informative about gene function. We exome sequenced 3,222 British Pakistani-heritage adults with high parental relatedness, discovering 1,111 rare-variant homozygous likely loss of function (rhLOF) genotypes predicted to disrupt (knockout) 781 genes. Based on depletion of rhLOF genotypes, we estimate that 13.6% of knockouts are incompatible with adult life, finding on average 1.6 heterozygous recessive lethal LOF variants per adult. Linking to lifelong health records, we observed no association of rhLOF genotypes with prescription- or doctor-consultation rate, and no disease-related phenotypes in 33 of 42 individuals with rhLOF genotypes in recessive Mendelian disease genes. Phased genome sequencing of a healthy PRDM9 knockout mother, her child and controls, showed meiotic recombination sites localised away from PRDM9-dependent hotspots, demonstrating PRDM9 redundancy in humans.

Genomics