Supervised classification enables rapid annotation of cell atlases, bioRxiv, 2019-02-05
Single cell technologies for profiling tissues or even entire organisms are rapidly being adopted. However, the manual process by which cell types are typically annotated in the resulting data is labor-intensive and increasingly rate-limiting for the field. Here we describe Garnett, an algorithm and accompanying software for rapidly annotating cell types in scRNA-seq and scATAC-seq datasets, based on an interpretable, hierarchical markup language of cell type-specific genes. Garnett successfully classifies cell types in tissue and whole organism datasets, as well as across species.
biorxiv genomics 200-500-users 2019New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania, bioRxiv, 2019-02-04
We conducted a genome-wide association study of host resistance to severe Plasmodium falciparum malaria in over 17,000 individuals from 11 malaria- endemic countries, undertaking a wide ranging analysis which identifies five replicable associations with genome-wide levels of evidence. Our findings include a newly implicated variant on chromosome 6 associated with risk of cerebral malaria, and the discovery of an erythroid-specific transcription start site underlying the association in ATP2B4. Previously reported HLA associations cannot be replicated in this dataset. We estimate substantial heritability of severe malaria (h2 ~ 23%), of which around 10% is explained by the currently identified associations. Our dataset will provide a major building block for future research on the genetic determinants of disease in these diverse human populations.
biorxiv genetics 0-100-users 2019Resistance gene cloning from a wild crop relative by sequence capture and association genetics, Nature Biotechnology, 2019-02-04
Disease resistance (R) genes from wild relatives could be used to engineer broad-spectrum resistance in domesticated crops. We combined association genetics with R gene enrichment sequencing (AgRenSeq) to exploit pan-genome variation in wild diploid wheat and rapidly clone four stem rust resistance genes. AgRenSeq enables R gene cloning in any crop that has a diverse germplasm panel.
nature biotechnology genetics 200-500-users 2019Systematic mapping of drug metabolism by the human gut microbiome, bioRxiv, 2019-02-04
The human gut microbiome harbors hundreds of bacterial species with diverse biochemical capabilities, making it one of nature's highest density, highest diversity bioreactors. Several drugs have been previously shown to be directly metabolized by the gut microbiome, but the extent of this phenomenon has not been systematically explored. Here, we develop a systematic screen for mapping the ability of the complex human gut microbiome to biochemically transform small molecules (MDM-Screen), and apply it to a library of 575 clinically used oral drugs. We show that 13% of the analyzed drugs, spanning 28 pharmacological classes, are metabolized by a single microbiome sample. In a proof-of-principle example, we show that microbiome-derived metabolism occurs in vivo, identify the genes responsible for it, and provide a possible link between its consequences and clinically observed features of drug bioavailability and toxicity. Our findings reveal a previously underappreciated role for the gut microbiome in drug metabolism, and provide a comprehensive framework for characterizing this important class of drug-microbiome interactions.
biorxiv microbiology 0-100-users 2019A primal role for balance in the development of coordinated locomotion, bioRxiv, 2019-02-02
Mature locomotion requires that animal nervous systems coordinate distinct groups of muscles. The pressures that guide the development of coordination are not well understood. We studied vertical locomotion in developing zebrafish to understand how and why coordination might emerge. We found that zebrafish used their pectoral fins and bodies synergistically to climb. As they developed, zebrafish came to coordinate their fins and bodies to climb with increasing postural stability. Fin-body synergies were absent in mutants without vestibular sensation, linking balance and coordination. Similarly, synergies were systematically altered following cerebellar lesions, identifying a neural substrate regulating fin-body coordination. Computational modeling illustrated how coordinated climbing could improve balance as zebrafish mature. Together these findings link the sense of balance to the maturation of coordinated locomotion. As they develop, zebrafish improve postural stability by optimizing fin-body coordination. We therefore propose that the need to balance drives the development of coordinated locomotion.
biorxiv neuroscience 100-200-users 2019An olfactory receptor gene underlies reproductive isolation in perfume-collecting orchid bees Supplemental Materials, bioRxiv, 2019-02-02
Speciation is facilitated by the evolution of reproductive barriers that prevent or reduce hybridization among diverging lineages. However, the genetic mechanisms that control the evolution of reproductive barriers remain elusive, particularly in natural populations. We identify a gene associated with divergence in chemical courtship signaling in a pair of nascent orchid bee lineages. Male orchid bees collect perfume compounds from flowers and other sources to subsequently expose during courtship display, thereby conveying information on species identity. We show that these two lineages exhibit differentiated perfume blends and that this change is associated with the rapid evolution of a single odorant receptor gene. Our study suggests that reproductive isolation evolved through divergence of a major barrier gene involved in chemically mediated pre-mating isolation via genetic coupling.
biorxiv evolutionary-biology 100-200-users 2019