Despite the wide range of skin pigmentation in humans, little is known about its genetic basis in global populations. Examining ethnically diverse African genomes, we identify variants in or near SLC24A5, MFSD12, DDB1, TMEM138, OCA2 and HERC2 that are significantly associated with skin pigmentation. Genetic evidence indicates that the light pigmentation variant at SLC24A5 was introduced into East Africa by gene flow from non-Africans. At all other loci, variants associated with dark pigmentation in Africans are identical by descent in southern Asian and Australo-Melanesian populations. Functional analyses indicate that MFSD12 encodes a lysosomal protein that affects melanogenesis in zebrafish and mice, and that mutations in melanocyte-specific regulatory regions near DDB1/TMEM138 correlate with expression of UV response genes under selection in Eurasians.

Background Africa is the origin of modern humans within the past 300 thousand years. To infer the complex demographic history of African populations and adaptation to diverse environments, we sequenced the genomes of 92 individuals from 44 indigenous African populations. Results Genetic structure analyses indicate that among Africans, genetic ancestry is largely partitioned by geography and language, though we observe mixed ancestry in many individuals, consistent with both short- and long-range migration events followed by admixture. Phylogenetic analysis indicates that the San genetic lineage is basal to all modern human lineages. The San and Niger-Congo, Afroasiatic, and Nilo-Saharan lineages were substantially diverged by 160 kya (thousand years ago). In contrast, the San and Central African rainforest hunter-gatherer (CRHG), Hadza hunter-gatherer, and Sandawe hunter-gatherer lineages were diverged by ~ 120–100 kya. Niger-Congo, Nilo-Saharan, and Afroasiatic lineages diverged more recently by ~ 54–16 kya. Eastern and western CRHG lineages diverged by ~ 50–31 kya, and the western CRHG lineages diverged by ~ 18–12 kya. The San and CRHG populations maintained the largest effective population size compared to other populations prior to 60 kya. Further, we observed signatures of positive selection at genes involved in muscle development, bone synthesis, reproduction, immune function, energy metabolism, and cell signaling, which may contribute to local adaptation of African populations. Conclusions We observe high levels of genomic variation between ethnically diverse Africans which is largely correlated with geography and language. Our study indicates ancient population substructure and local adaptation of Africans. Electronic supplementary material The online version of this article (10.1186/s13059-019-1679-2) contains supplementary material, which is available to authorized users.

Recent technological breakthroughs have made it possible to measure RNA expression at the single-cell level, thus paving the way for exploring expression heterogeneity among individual cells. Current single-cell RNA sequencing (scRNA-seq) protocols are complex and introduce technical biases that vary across cells, which can bias downstream analysis without proper adjustment. To account for cell-to-cell technical differences, we propose a statistical framework, TASC (Toolkit for Analysis of Single Cell RNA-seq), an empirical Bayes approach to reliably model the cell-specific dropout rates and amplification bias by use of external RNA spike-ins. TASC incorporates the technical parameters, which reflect cell-to-cell batch effects, into a hierarchical mixture model to estimate the biological variance of a gene and detect differentially expressed genes. More importantly, TASC is able to adjust for covariates to further eliminate confounding that may originate from cell size and cell cycle differences. In simulation and real scRNA-seq data, TASC achieves accurate Type I error control and displays competitive sensitivity and improved robustness to batch effects in differential expression analysis, compared to existing methods. TASC is programmed to be computationally efficient, taking advantage of multi-threaded parallelization. We believe that TASC will provide a robust platform for researchers to leverage the power of scRNA-seq.

The genomics era has accelerated our understanding of how genetic and epigenetic factors influence both normal variable traits and disease risk in humans. However, the majority of “omics” studies have focused on individuals living in urban centers, primarily from Europe and Asia, neglecting much of the genetic and environmental variation that exists across worldwide populations. Comparative studies of gene regulation in ethnically diverse populations are informing our understanding of how evolutionary forces have shaped the genetic and molecular mechanisms underlying complex traits, and studying gene expression in different environmental contexts is enabling the dissection of disease-related pathways such as immune response. Such approaches are vital to the equitable application of genomics and medicine.

Almost all the world's food is grown in open fields, where plant phenotypes can be very different from those observed in greenhouses. Geneticists and agronomists studying food crops routinely detect, measure, and classify a wide variety of phenotypes in fields that contain many visually distinct types of a single crop. Augmenting humans in these tasks by automatically interpreting images raises some important and nontrivial challenges for research in computer vision. Nonetheless, the rewards for overcoming these obstacles could be exceptionally high for today's 7 billion people, let alone the 9.6 billion projected by 2050 (United Nations Department of Economic and Social Affairs, Population Division, World Population Prospects: The 2012 Revision). To stimulate dialog between researchers in computer vision and those in genetics and agronomy, we offer our views on three computational challenges that are central to many phenotyping tasks. These are disambiguating one plant from another; assigning an individual plant's organs to it; and identifying field phenotypes from those shown in archival images. We illustrate these challenges with annotated photographs of maize highlighting the regions of interest. We also describe some of the experimental, logistical, and photographic constraints on image collection and processing. While collecting the data sets needed for algorithmic experiments requires sustained collaboration and funding, the images we show and have posted should allow one to consider the problems, think of possible approaches, and decide on the next steps.

Complex phenotypes are of growing importance in agriculture and medicine. In Zea mays, the most widely produced crop in the world (United States Department of Agriculture. World Agricultural Production. United States Department of Agriculture, Foreign Agricultural Service, Washington, 2015), the disease lesion mimic mutants produce regions of discolored or necrotic tissue in otherwise healthy plants. These mutants are of particular interest due to their apparent action on immune response pathways, providing insight into how plants protect against infectious agents. These phenotypes vary considerably as a function of genotype and environmental conditions, making them a rich, though challenging, phenotypic problem. To segment and quantitate these lesions, we present a novel cascade of adaptive algorithms able to accurately segment the diversity of Z. mays lesions. First, multiresolution analysis of the image allows for salient features to be detected at multiple scales. Next, gradient vector diffusion enhances relevant gradient vectors while suppressing noise. Finally, an active contour algorithm refines the lesion boundary, producing a final segmentation for each lesion. We compare the results from this cascade with manual segmentations from human observers, demonstrating that our algorithm is comparable to humans while having the potential to speed analysis by several orders of magnitude.

Background Mapping of quantitative trait loci (QTL) associated with molecular phenotypes is a powerful approach for identifying the genes and molecular mechanisms underlying human traits and diseases, though most studies have focused on individuals of European descent. While important progress has been made to study a greater diversity of human populations, many groups remain unstudied, particularly among indigenous populations within Africa. To better understand the genetics of gene regulation in East Africans, we perform expression and splicing QTL mapping in whole blood from a cohort of 162 diverse Africans from Ethiopia and Tanzania. We assess replication of these QTLs in cohorts of predominantly European ancestry and identify candidate genes under selection in human populations. Results We find the gene regulatory architecture of African and non-African populations is broadly shared, though there is a considerable amount of variation at individual loci across populations. Comparing our analyses to an equivalently sized cohort of European Americans, we find that QTL mapping in Africans improves the detection of expression QTLs and fine-mapping of causal variation. Integrating our QTL scans with signatures of natural selection, we find several genes related to immunity and metabolism that are highly differentiated between Africans and non-Africans, as well as a gene associated with pigmentation. Conclusion Extending QTL mapping studies beyond European ancestry, particularly to diverse indigenous populations, is vital for a complete understanding of the genetic architecture of human traits and can reveal novel functional variation underlying human traits and disease.

Recent technological breakthroughs have made it possible to measure RNA expression at the single-cell level, thus paving the way for exploring expression heterogeneity among individual cells. Current single-cell RNA sequencing (scRNA-seq) protocols are complex and introduce technical biases that vary across cells, which can bias downstream analysis without proper adjustment. To account for cell-to-cell technical differences, we propose a statistical framework, TASC (Toolkit for Analysis of Single Cell RNA-seq), an empirical Bayes approach to reliably model the cell-specific dropout rates and amplification bias by use of external RNA spike-ins.