CEGA: a method for inferring natural selection by comparative population genomic analysis across species.

We developed maximum likelihood method for detecting positive selection or balancing selection using multilocus or genomic polymorphism and divergence data from two species. The method is especially useful for investigating natural selection in noncoding regions. Simulations demonstrate that the method outperforms existing methods in detecting both positive and balancing selection.

Neuroprotective Effects of Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cell Extracellular Vesicles in Ischemic Stroke Models.

Background: Stroke represents the second leading cause of death and the primary cause of long-term disability in humans. The transplantation of mesenchymal stem cells (MSC) reportedly improves functional outcomes in animal models of cerebral ischemia. Here, we evaluate the neuroprotective potential of extracellular vesicles secreted from human-induced pluripotent stem cell-derived mesenchymal stem cells (hiPS-MSC-EV) using preclinical cell-based and animal-based models of ischemic strokes.

Dyslexia-related loci are significantly associated with language and literacy in Chinese-English bilingual Hong Kong Chinese twins.

A recent genome-wide association study on dyslexia in 51,800 affected European adults and 1,087,070 controls detected 42 genome-wide significant single nucleotide variants (SNPs). The association between rs2624839 in SEMA3F and reading fluency was replicated in a Chinese cohort. This study explores the genetic overlap between Chinese and English word reading, vocabulary knowledge and spelling, and aims at replicating the association in a unique cohort of bilingual (Chinese-English) Hong Kong Chinese twins.

Genomic inference of a severe human bottleneck during the Early to Middle Pleistocene transition.

Population size history is essential for studying human evolution. However, ancient population size history during the Pleistocene is notoriously difficult to unravel. In this study, we developed a fast infinitesimal time coalescent process (FitCoal) to circumvent this difficulty and calculated the composite likelihood for present-day human genomic sequences of 3154 individuals.

A new hypothesis on BV etiology: dichotomous and crisscrossing categorization of complex versus simple on healthy versus BV vaginal microbiomes.

BV may influence as many as one-third of women, but its etiology remains unclear. A traditional view is that dominance by is the hallmark of a healthy vaginal microbiome and lack of dominance may make women BV-prone. Recent studies show that the human VMs can be classified into five major types, four of which possess type-specific dominant species of .

Polygenic adaptation leads to a higher reproductive fitness of native Tibetans at high altitude.

The adaptation of Tibetans to high-altitude environments has been studied extensively. However, the direct assessment of evolutionary adaptation, i.e.

DNA methylation age acceleration contributes to the development and prediction of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is prevalent in the aging society. Despite body weight reduction, the prevalence of NAFLD has been increasing with aging for unknown reasons. Here, we investigate the association of DNA methylation age acceleration, a hallmark of aging, with risk of NAFLD.

S1P-S1PR3-RAS promotes the progression of S1PR3 TAL1 T-cell acute lymphoblastic leukemia that can be effectively inhibited by an S1PR3 antagonist.

TAL1 T-cell acute lymphoblastic leukemia (T-ALL) is a distinct subtype of leukemia with poor outcomes. Through the cooperation of co-activators, including RUNX1, GATA3, and MYB, the TAL1 oncoprotein extends the immature thymocytes with autonomy and plays an important role in the development of T-ALL. However, this process is not yet well understood.

Comparative Genomic Analysis Identifies Great-Ape-Specific Structural Variants and Their Evolutionary Relevance.

During the origin of great apes about 14 million years ago, a series of phenotypic innovations emerged, such as the increased body size, the enlarged brain volume, the improved cognitive skill, and the diversified diet. Yet, the genomic basis of these evolutionary changes remains unclear. Utilizing the high-quality genome assemblies of great apes (including human), gibbon, and macaque, we conducted comparative genome analyses and identified 15,885 great ape-specific structural variants (GSSVs), including eight coding GSSVs resulting in the creation of novel proteins (e.

SONAR enables cell type deconvolution with spatially weighted Poisson-Gamma model for spatial transcriptomics.

Recent advancements in spatial transcriptomic technologies have enabled the measurement of whole transcriptome profiles with preserved spatial context. However, limited by spatial resolution, the measured expressions at each spot are often from a mixture of multiple cells. Computational deconvolution methods designed for spatial transcriptomic data rarely make use of the valuable spatial information as well as the neighboring similarity information.

Inter-tissue communication of mitochondrial stress and metabolic health.

Mitochondria function as a hub of the cellular metabolic network. Mitochondrial stress is closely associated with aging and a variety of diseases, including neurodegeneration and cancer. Cells autonomously elicit specific stress responses to cope with mitochondrial stress to maintain mitochondrial homeostasis.

Smurf1 and Smurf2 mediated polyubiquitination and degradation of RNF220 suppresses Shh-group medulloblastoma.

Sonic hedgehog (Shh)-group medulloblastoma (MB) (Shh-MB) encompasses a clinically and molecularly distinct group of cancers originating from the developing nervous system with aberrant high Shh signaling as a causative driver. We recently reported that RNF220 is required for sustained high Shh signaling during Shh-MB progression; however, how high RNF220 expression is achieved in Shh-MB is still unclear. In this study, we found that the ubiquitin E3 ligases Smurf1 and Smurf2 interact with RNF220, and target it for polyubiquitination and degradation.

PhyloVelo enhances transcriptomic velocity field mapping using monotonically expressed genes.

Single-cell RNA sequencing (scRNA-seq) is a powerful approach for studying cellular differentiation, but accurately tracking cell fate transitions can be challenging, especially in disease conditions. Here we introduce PhyloVelo, a computational framework that estimates the velocity of transcriptomic dynamics by using monotonically expressed genes (MEGs) or genes with expression patterns that either increase or decrease, but do not cycle, through phylogenetic time. Through integration of scRNA-seq data with lineage information, PhyloVelo identifies MEGs and reconstructs a transcriptomic velocity field.

Landscape genomics analysis provides insights into future climate change-driven risk in rhesus macaque.

Climate change significantly affects the suitability of wildlife habitats. Thus, understanding how animals adapt ecologically and genetically to climate change is important for targeted species protection. Rhesus macaques (Macaca mulatta) are widely distributed and multi-climatically adapted primates.

Integrative Omics Reveals Rapidly Evolving Regulatory Sequences Driving Primate Brain Evolution.

Although the continual expansion of the brain during primate evolution accounts for our enhanced cognitive capabilities, the drivers of brain evolution have scarcely been explored in these ancestral nodes. Here, we performed large-scale comparative genomic, transcriptomic, and epigenomic analyses to investigate the evolutionary alterations acquired by brain genes and provide comprehensive listings of innovatory genetic elements along the evolutionary path from ancestral primates to human. The regulatory sequences associated with brain-expressed genes experienced rapid change, particularly in the ancestor of the Simiiformes.

Light-Driven Spatiotemporal Pickering Emulsion Droplet Manipulation Enabled by Plasmonic Hybrid Microgels.

The past decades have witnessed the development of various stimuli-responsive materials with tailored functionalities, enabling droplet manipulation through external force fields. Among different strategies, light exhibits excellent flexibility for contactless control of droplets, particularly in three-dimensional space. Here, we present a facile synthesis of plasmonic hybrid microgels based on the electrostatic heterocoagulation between cationic microgels and anionic Au nanoparticles.

Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci.

Human ear morphology, a complex anatomical structure represented by a multidimensional set of correlated and heritable phenotypes, has a poorly understood genetic architecture. In this study, we quantitatively assessed 136 ear morphology traits using deep learning analysis of digital face images in 14,921 individuals from five different cohorts in Europe, Asia, and Latin America. Through GWAS meta-analysis and C-GWASs, a recently introduced method to effectively combine GWASs of many traits, we identified 16 genetic loci involved in various ear phenotypes, eight of which have not been previously associated with human ear features.

The complete and fully-phased diploid genome of a male Han Chinese.

Since the release of the complete human genome, the priority of human genomic study has now been shifting towards closing gaps in ethnic diversity. Here, we present a fully phased and well-annotated diploid human genome from a Han Chinese male individual (CN1), in which the assemblies of both haploids achieve the telomere-to-telomere (T2T) level. Comparison of this diploid genome with the CHM13 haploid T2T genome revealed significant variations in the centromere.

On-demand light-driven release of droplets stabilized a photoresponsive fluorosurfactant.

Water-in-oil droplets have emerged as promising microreactors for high-throughput biochemical analysis due to their features of reduced sample consumption and automated operation. For a typical screening application, droplets are often trapped for continuous monitoring of the reaction over an extended period, followed by the selective retrieval of targeted droplets based on the after-effect of biochemical reactions. While techniques for droplet trapping are well developed, retrieval of targeted droplets mainly demands complicated device fabrication or sophisticated control.