ASU Scholarship Showcase

Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy.

Contemporary human populations conform to ecogeographic predictions that animals will become more compact in cooler climates and less compact in warmer ones. However, it remains unclear to what extent this pattern reflects plastic responses to current environments or genetic differences among populations. Analyzing anthropometric surveys of 232,684 children and adults from across 80 ethnolinguistic groups in sub-Saharan Africa, Asia and the Americas, we confirm that body surface-to-volume correlates with contemporary temperature at magnitudes found in more latitudinally diverse samples (Adj. R² = 0.14-0.28). However, far more variation in body surface-to-volume is attributable to genetic population structure (Adj. R² = 0.50-0.74). Moreover, genetic population structure accounts for nearly all of the observed relationship between contemporary temperature and body surface-to-volume among children and adults. Indeed, after controlling for population structure, contemporary temperature accounts for no more than 4% of the variance in body form in these groups. This effect of genetic affinity on body form is also independent of other ecological variables, such as dominant mode of subsistence and household wealth per capita. These findings suggest that the observed fit of human body surface-to-volume with current climate in this sample reflects relatively large effects of existing genetic population structure of contemporary humans compared to plastic response to current environments.

Background: The transition from the home to college is a phase in which emerging adults shift toward more unhealthy eating and physical activity patterns, higher body mass indices, thus increasing risk of overweight/obesity. Currently, little is understood about how changing friendship networks shape weight gain behaviors. This paper describes the recruitment, data collection, and data analytic protocols for the SPARC (Social impact of Physical Activity and nutRition in College) study, a longitudinal examination of the mechanisms by which friends and friendship networks influence nutrition and physical activity behaviors and weight gain in the transition to college life.

Methods: The SPARC study aims to follow 1450 university freshmen from a large university over an academic year, collecting data on multiple aspects of friends and friendship networks. Integrating multiple types of data related to student lives, ecological momentary assessments (EMAs) are administered via a cell phone application, devilSPARC. EMAs collected in four 1-week periods (a total of 4 EMA waves) are integrated with linked data from web-based surveys and anthropometric measurements conducted at four times points (for a total of eight data collection periods including EMAs, separated by ~1 month). University databases will provide student card data, allowing integration of both time-dated data on food purchasing, use of physical activity venues, and geographical information system (GIS) locations of these activities relative to other students in their social networks.

Discussion: Findings are intended to guide the development of more effective interventions to enhance behaviors among college students that protect against weight gain during college.

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats.

Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits.

Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation.

We present a phylogeographic study of at least six reproductively isolated lineages of new world harvester ants within the Pogonomyrmex barbatus and P. rugosus species group. The genetic and geographic relationships within this clade are complex: Four of the identified lineages show genetic caste determination (GCD) and are divided into two pairs. Each pair has evolved under a mutualistic system that necessitates sympatry. These paired lineages are dependent upon one another because their GCD requires interlineage matings for the production of F1 hybrid workers, and intralineage matings are required to produce queens. This GCD system maintains genetic isolation among these interdependent lineages, while simultaneously requiring co-expansion and emigration as their distributions have changed over time. It has also been demonstrated that three of these four GCD lineages have undergone historical hybridization, but the narrower sampling range of previous studies has left questions on the hybrid parentage, breadth, and age of these groups. Thus, reconstructing the phylogenetic and geographic history of this group allows us to evaluate past insights and hypotheses and to plan future inquiries in a more complete historical biogeographic context. Using mitochondrial DNA sequences sampled across most of the morphospecies’ ranges in the U.S.A. and Mexico, we conducted a detailed phylogeographic study. Remarkably, our results indicate that one of the GCD lineage pairs has experienced a dramatic range expansion, despite the genetic load and fitness costs of the GCD system. Our analyses also reveal a complex pattern of vicariance and dispersal in Pogonomyrmex harvester ants that is largely concordant with models of late Miocene, Pliocene, and Pleistocene range shifts among various arid-adapted taxa in North America.

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C^low and Ly6C^hi) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E₂ is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6C^low Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signaling and subsequently inhibits Ly6C^low Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE₂/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6C^low Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF–TF interactions that form TF logics in regulating target genes. By combining cis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs. We evaluated the newly developed methodology using simulation, comparison and application studies, and the results not only show their consistence with existing knowledge, but also demonstrate its ability to accurately reconstruct TRNs in biological complex systems.

Background: Prior studies have shown that using uterotonics to augment or induce labor before arrival at comprehensive Emergency Obstetric and Neonatal Care (CEmONC) settings (henceforth, “outside uterotonics”) may contribute to perinatal mortality in low- and middle-income countries. We estimate its effect on perinatal mortality in rural Bangladesh.

Methods: Using hospital records (23986 singleton term births, Jan 1, 2009-Dec 31, 2015) from rural Bangladesh, we use a logistic regression model to estimate the increased risk of perinatal death from uterotonics administered outside a CEmONC facility.

Results: Among term births (≥37 weeks gestation), the risk of perinatal death adjusted for key confounders is significantly increased among women reporting uterotonic use outside of CEmONC (OR = 3 · 0, 95 % CI = 2 · 4,3 · 7). This increased risk is particularly high for fresh stillbirths (OR = 4 · 0, 95 % CI = 3 · 0,5 · 3) and intrapartum-related causes of early neonatal deaths (birth asphyxia) (OR = 3 · 1, 95 % CI = 2 · 2,4 · 5).

Conclusions: In this sample, outside uterotonic use was associated with substantially increased risk of fresh stillbirths, deaths due to birth asphyxia, and all perinatal deaths. In settings of high uterotonic use outside of controlled settings, substantial improvement in both stillbirth and early neonatal mortality may be made by reducing such use.

It remains challenging to predict regulatory variants in particular tissues or cell types due to highly context-specific gene regulation. By connecting large-scale epigenomic profiles to expression quantitative trait loci (eQTLs) in a wide range of human tissues/cell types, we identify critical chromatin features that predict variant regulatory potential. We present cepip, a joint likelihood framework, for estimating a variant’s regulatory probability in a context-dependent manner. Our method exhibits significant GWAS signal enrichment and is superior to existing cell type-specific methods. Furthermore, using phenotypically relevant epigenomes to weight the GWAS single-nucleotide polymorphisms, we improve the statistical power of the gene-based association test.