Biology subjects

Jiang, W.

Publications and source records attributed to Jiang, W..

At least 145 records · Page 8Linked to original sources

bioRxiv2022

A wearable platform for closed-loop stimulation and recording of single- neuron and local field potential activity in freely-moving humans

Advances in technologies that can record and stimulate deep-brain activity in humans have led to impactful discoveries within the field of neuroscience and contributed to the development of novel therapies for neurological and psychiatric disorders. Further progress, however, has been hindered by device limitations in that recording of single-neuron activity during freely-moving behaviors in humans has not been possible. Additionally, implantable neurostimulation devices, currently approved for human use, have limited stimulation programmability and lack full-duplex bi-directional capability. Here, we developed a wearable bi-directional closed-loop neuromodulation system (Neuro-stack) and used it to record single-neuron and local field potential activity during stationary and ambulatory behavior in humans. Together with a highly flexible and customizable stimulation capability, the Neuro-stack provides an opportunity to investigate the neurophysiological basis of disease, develop improved responsive neuromodulation therapies, explore brain function during naturalistic behaviors in humans, and consequently, bridge decades of neuroscientific findings across species.

neuroscience↗

bioRxiv2022

Impact of various vaccine boosters on neutralization against Omicron following prime vaccinations with inactivated or adenovirus-vectored vaccine

Since the first report on November 24, 2021, the Omicron SARS-CoV-2 variant is now overwhelmingly spreading across the world. Two SARS-CoV-2 inactivated vaccines (IAVs), one recombinant protein subunit vaccine (PRV), and one adenovirus-vectored vaccine (AdV) have been widely administrated in many countries including China to pursue herd immunity. Here we investigated cross-neutralizing activities in 341 human serum specimens elicited by full-course vaccinations with IAV, PRV and AdV, and by various vaccine boosters following prime IAV and AdV vaccinations. We found that all types of vaccines induced significantly lower neutralizing antibody titers against the Omicron variant than against the prototype strain. For prime vaccinations with IAV and AdV, heterologous boosters with AdV and PRV, respectively, elevated serum Omicron-neutralizing activities to the highest degrees. In a mouse model, we further demonstrated that among a series of variant-derived RBD-encoding mRNA vaccine boosters, it is only the Omicron booster that significantly enhanced Omicron neutralizing antibody titers compared with the prototype booster following a prime immunization with a prototype S-encoding mRNA vaccine candidate. In summary, our systematical investigations of various vaccine boosters inform potential booster administrations in the future to combat the Omicron variant.

immunology↗

bioRxiv2022

Core Transcription Programs Controlling Injury-Induced Neurodegeneration of Retinal Ganglion Cells

Neurodegenerative diseases are characterized by neuronal death and regenerative failure. However, gene regulatory programs governing how initial neuronal injuries lead to neuronal death remain poorly understood. In adult mice, optic nerve crush (ONC) injury, which severs all axons of retinal ganglion cells (RGCs), results in massive death of axotomized RGCs and regenerative failure of survivors. We performed an in vivo CRISPR/Cas9-based genome-wide screen of 1893 transcription factors (TFs) to seek repressors of RGC survival and axon regeneration following ONC. In parallel, we profiled the epigenetic and transcriptional landscapes of injured RGCs by ATAC-seq and RNA-seq to identify critical injury responsive TFs and their targets. Remarkably, these independent analyses converged on a set of four ATF/CEBP transcription factors - ATF3, ATF4, C/EBP{gamma} and CHOP (Ddit3) - as critical regulators of survival. Further studies indicate that these TFs contribute to two pro-death transcriptional programs: ATF3/CHOP preferentially regulate pathways activated by cytokines and innate immunity, whereas ATF4/C/EBP{gamma} regulate pathways engaged by intrinsic neuronal stressors. Manipulation of these TFs also protects RGCs in an experimental model of glaucoma, a prevalent disease in which RGCs die. Together, our results reveal core transcription programs that transform an initial axonal insult into a degenerative result and suggest novel strategies for treating neurodegenerative diseases.

neuroscience↗

bioRxiv2022

Scale Bar of Aging Trajectories for Screening Personal Rejuvenation Treatments

Although aging is an increasingly severe healthy, economic, and social global problem, it is far from well-modeling aging due to the aging processs complexity. To promote the aging modeling, here we did the quantitative measurement based on aging blood transcriptome. Specifically, the aging blood transcriptome landscape was constructed through ensemble modeling in a cohort of 505 people, and 1138 age-related genes were identified. To assess the aging rate in the linear dimension of aging, we constructed a simplified linear aging clock, which distinguished fast-aging and slow-aging populations and showed the differences in the composition of immune cells. Meanwhile, the non-linear dimension of aging revealed the transcriptome fluctuations with a crest around the age of 40 and showed that this crest came earlier and was more vigorous in the fast-aging population. Moreover, the aging clock was applied to evaluate the rejuvenation effect of molecules in vitro, such as Nicotinamide Mononucleotide (NMN) and Metformin. In sum, this study developed a de novo aging clock to evaluate agedependent precise medicine by revealing its fluctuation nature based on comprehensively mining the aging blood transcriptome, promoting the development of personal aging monitoring and anti-aging therapies.

bioengineering↗

bioRxiv2022

Structural insights into the galanin receptors signaling

Galanin is a biologically active neuropeptide, and functions through three distinct G protein-coupled receptors (GPCRs), namely GALR1, GALR2 and GLAR3. GALR signaling plays important roles in regulating various physiological processes such as energy metabolism, neuropathic pain, epileptic activity, and sleep homeostasis. GALR1 and GALR3 signal through the Gi/o pathway, whereas GALR2 signals mainly through the Gq/11 pathway. However, the molecular basis for galanin recognition and G protein selectivity of GALRs remains poorly understood. Here, we report the cryoelectron microscopy structures of the GALR1-Go and the GALR2-Gq complexes bound to the endogenous ligand galanin or spexin. The galanin peptide mainly adopts an alpha helical structure, which binds at the extracellular vestibule of the receptors, nearly parallel to the membrane plane without penetrating deeply into the receptor core. Structural analysis combined with functional studies reveals important structural determinants for the G protein selectivity of GALRs as well as other class A GPCRs. In addition, we show that the zinc ion is a negative allosteric regulator of GALR1 but not GALR2. Our studies provide insight into the mechanisms of G protein selectivity of GPCRs and highlight potential novel function of the neuromodulator zinc ion as a modulator of GPCR signaling in the central nervous system. Significance StatementGalanin exerts various physiological functions through galanin receptors, including antinociceptive activity, depression and sleep. Here, we reveal a distinct binding site and binding pose of galanin peptide in galanin receptors from that of the published structures of peptide-bound GPCRs. Moreover, our work show that the neuromodulator zinc ion negatively modulates galanin signaling in the central nervous system, and further advances our understanding of mechanisms of G protein selectivity of GPCRs. These unique features of galanin receptors can be exploited for rational design of subtype selective ligands for treatments of neurological disorders.

neuroscience↗

bioRxiv2022

Unifying Gene Expression Complexity and Cellular Operational Efficiency: Application of the Locality and Caching Principles via a Cell-to-Computer Analogy

Gene expression is time-consuming and sequentially more so from bacteria to yeast to human, rendering human cells vulnerable to proteomic-response and operational latency. Computers once suffered such latency, imposed by much-slower information retrieval (hard-drive (HD) to memory to central-processing-unit (CPU)) than CPU execution. Optimization principles, namely, spatiotemporal-locality-principles that control specialized user-programs and caching that controls operating system (OS) kernel (the HD-CPU information flow channel), successfully mitigated the latency by gearing the memory towards near-future or high-priority CPU needs. We report evidence that the principles similarly act in cellular latency-mitigation via analogizing genome-mRNA-protein gene-expression to HD-memory-CPU information-retrieval, and transcriptome to memory. First, temporal-locality-principle is equivalent to mRNA stabilization-by-translation regulation and controls specialized cellular functions. Second, caching is equivalent to cytoplasmic mRNA sequestration. Highly sequestered mRNAs defy the locality-principle. In both cells and computers, caching controls the information channels; gene expression machinery and their regulators, i.e., the cellular channel (OS-kernel equivalent) that regulates arguably all cellular processes, are top sequestered mRNAs. Third, mRNA-caching contributes to the mRNA-protein expression discrepancy. Thus, locality and caching principles control specialized and core cellular functions, respectively, orchestrating transcriptome regulation and bridging it to cellular operational efficiency.

systems biology↗

bioRxiv2022

Microscopic and ultramicroscopic anatomical characteristics of root nodules in Podocarpus macrophyllus during development

To understand the morphological and structural characteristics of root nodules in Podocarpus macrophyllus and their development, this study prepared P. macrophyllus root nodule samples at the young, mature, and senescent stages. Optical microscopy and transmission electron microscopy (SEM) revealed that new nodules can be formed on roots and senescent nodules; new nodules formed on the roots are nearly spherical and have an internal structure similar to finite nodules; new nodules on senescent nodules are formed by extension and differentiation of the vascular cylinder of the original nodules; and these new nodules are nested at the base of the original nodules, which create growth space for new nodules by dissociating the cortical tissue; clusters of nodules are formed after extensive accumulation, and the growth pattern is similar to that of infinite nodules; the symbiotic bacteria of P. macrophyllus root nodules mainly invade from the epidermal intercellular space of the roots and migrate along the intercellular space of the nodule cortex; infected nodule cortex cells have a well-developed inner membrane system and enlarged and loose nuclei; and unique Frankia vesicles, and rhizobia cysts, and bacteriophages can all develop. Compared with common leguminous and nonleguminous plant nodules, P. macrophyllus root nodules are more complex in morphology, structure and composition. From the perspective of plant system evolution, the rhizobium nodules in leguminous angiosperms and Frankia nodules in nonleguminous angiosperms are most likely two branches derived from the nodules in gymnosperms, such as P. macrophyllus. The conclusions of this study can provide a theoretical basis for the developmental biology of P. macrophyllus root nodules and the evolutionary pattern of plant symbionts. HighlightsWe discuss from the perspective of cell developmental biology, the rhizobium nodules in leguminous angiosperms and Frankia nodules in nonleguminous angiosperms are most likely two branches derived from the nodules in gymnosperms, such as Podocarpus macrophyllus.

developmental biology↗

bioRxiv2021

Structure of Vibrio phage XM1, a simple contractile DNA injection machine

Antibiotic resistance poses a growing risk to public health requiring new tools to combat pathogenic bacteria. Contractile injection systems, including bacteriophage tails, pyocins, and bacterial type VI secretion systems, can efficiently penetrate cell envelopes and become potential antibacterial agents. Bacteriophage XM1 is a dsDNA virus belonging to the Myoviridae family and infecting Vibrio bacteria. The XM1 virion, made of 18 different proteins, consists of an icosahedral head and a contractile tail, terminated with a baseplate. Here we report cryo-EM reconstructions of all components of the XM1 virion and describe atomic structures of 14 XM1 proteins. The XM1 baseplate is composed of a central hub surrounded by six wedge modules to which twelve spikes are attached. The XM1 tail contains a fewer number of smaller proteins compared with other reported phage baseplates, depicting the minimum requirements for building an effective cell-envelope-penetrating machine. We describe the tail sheath structure in the pre-infection post-infection states and its conformational changes during infection. In addition, we report, for the first time, the in situ structure of the phage neck region to near-atomic resolution. Based on these structures, we propose mechanisms of virus assembly and infection.

molecular biology↗

bioRxiv2021

Lipids in the Piezo1 channel pore: gating mechanism, or simulation artifact?

Multiscale molecular dynamics (MD) simulations using Martini coarse-grained (CG) and all-atom (AA) forcer fields are commonly used in membrane protein studies. In particular, reverse-mapping an equilibrated CG model to an AA model offers an efficient way for preparing large membrane protein systems with complex protein shapes and lipid compositions. Here, we report that this hybrid CG-equilibrium-AA-production protocol may artificially increase lipid density and decrease hydration in ion channel pores walled with transmembrane gaps. To understand the origin of this conundrum, we conducted replicas of CG, AA, and reverse-mapped AA simulations of the pore domain of the mechanosensitive Piezo1 channel in a non-conducting conformation. Lipid/water density analysis and free energy calculations reveal that the lack of initial pore hydration allows adjacent lipids to enter the pore lumen through gaps between pore helices during CG simulation. Due to the mismatch between CG and AA lipid kinetics, these pore lipids remain trapped in the subsequent AA simulations, despite unfavorable binding free energy. We tested several CG equilibrium protocols and found that a protocol restraining the whole lipid produces pore hydration consistent with AA results, thus eliminating this artifact for further studies of lipid gating and protein-lipid interactions. WHY IT MATTERSMembrane-embedded proteins constantly interact with lipid molecules. Computational molecular dynamics simulations have become an indispensable tool for investigating the role of such protein-lipid interactions. Using mechanosensitive Piezo1 channel as model, we found that subtle differences in solvation and equilibrium protocols between coarse-grained and all-atom MD simulations can result in different lipid densities inside the channel pore. We identify the underlying cause of this discrepancy and propose alternative protocols to avoid this artifact.

biophysics↗

bioRxiv2021

Identification and Characterization of Stem Cells in Mammalian Esophageal Stratified Squamous Epithelia

Somatic stem cells are essential for maintenance of cell proliferation-differentiation homeostasis in organs. Despite the importance, how the esophageal epithelium that executes its self-renewal and maintenance remains elusive. In this study, using 5-bromo-2-deoxyuridine (BrdU) label-chase in rat and rat esophageal keratinocyte cell line-derived organoids together with genome-wide DNA methylation profiling and single-cell RNA sequencing (scRNA-seq), we identify slow cycling/quiescent stem cell population that contain high levels of hemidesmosome (HD)s and low levels of Wnt signaling localized spatially and randomly at the basal layer of the esophageal epithelium. Pseudo-time cell trajectory from scRNA-seq indicates that cell fates begin from quiescent basal cells (the stem cells) of the basal layer that produce proliferating and/or differentiating cells in the basal layer, which, in turn, progress into differentiating cells in the suprabasal layer, ultimately transforming into differentiated keratinocytes in the differentiated layer. Perturbations of HD component expressions and/or Wnt signaling reduce stem cell in the basal layer of esophageal keratinocyte organoids, resulting in alterations of organoid formation rate, size, morphogenesis and proliferation-differentiation homeostasis. Furthermore, we show that not only high levels of HDs and low levels of Wnt signaling but also an interplay between HD and Wnt signaling defined stem cells of the basal layer in the esophageal squamous epithelium. Hence, HDs and Wnt signaling are the critical determinants for defining stem cells of the basal layer required for proliferation-differentiation homeostasis and maintenance in the mammalian esophageal squamous epithelium.

cell biology↗

bioRxiv2021

Bone marrow mesenchymal stem cells stimulated by tumor necrosis factor-α can promote the repair of fatty liver cell oxidative stress injury and fatty liver ischemia-reperfusion injury

Mesenchymal stem cells (MSCs) have great prospects for the treatment of ischemia-reperfusion injury (IRI) after liver transplantation. At this stage, the main factor limiting MSCs in the treatment of fatty liver IRI of the donor liver is the residence time of stem cells at the site of inflammatory injury. This study investigated whether bone marrow mesenchymal stem cells (BMSCs) stimulated by tumor necrosis factor- (TNF-) can promote the repair of fatty liver cell oxidative stress injury and fatty liver IRI in rats. The results indicated the BMSCs treatment group stimulated by TNF- had lower indexes and significantly improved oxidative stress damage in vitro through Transwell chamber co-culture experiment, compared with the control group. In vivo, compared with the PBS group and the BMSCs group, the indexes of the BMSCs treatment group stimulated by TNF- were reduced, and the degree of tissue damage was significantly reduced. BMSCs can repair fatty liver cell oxidative stress injury and fatty liver IRI, however, BMSCs stimulated by TNF- can promote the repair of tissues and cells.

cell biology↗

bioRxiv2021

Cold protection allows local cryotherapy in a clinical-relevant model of traumatic optic neuropathy

Therapeutic hypothermia (TH) is potentially an important therapy for central nervous system (CNS) trauma. However, its clinical application remains controversial, hampered by two major factors: 1) Many of the CNS injury sites, such as the optic nerve (ON), are deeply buried, preventing access for local TH. The alternative is to apply TH systemically, which significantly limits the applicable temperature range. 2) Even with possible access for "local refrigeration", cold-induced cellular damage offsets the benefit of TH. Here we present a clinically translatable model of traumatic optic neuropathy (TON) by applying clinical trans-nasal endoscopic surgery to goats and non-human primates. This model faithfully recapitulates clinical features of TON such as the injury site (pre-chiasmatic ON), the spatiotemporal pattern of neural degeneration, and the accessibility of local treatments with large operating space. We also developed a computer program to simplify the endoscopic procedure and expand this model to other large animal species. Moreover, applying a cold-protective treatment, inspired by our previous hibernation research, enables us to deliver deep hypothermia (4{degrees}C) locally to mitigate inflammation and metabolic stress (indicated by the transcriptomic changes after injury) without cold-induced cellular damage, and confers prominent neuroprotection both structurally and functionally. Intriguingly, neither treatment alone was effective, demonstrating that in situ deep hypothermia combined with hibernation-mimicking cold protection constitutes a breakthrough for TH as a therapy for TON and other CNS traumas.

neuroscience↗

bioRxiv2021

Emergence of an adaptive epigenetic cell state in human bladder urothelial carcinoma evolution

Intratumor heterogeneity (ITH) of bladder cancer (BLCA) facilitates therapy resistance and immune evasion to affect clinical prognosis directly. However, the molecular and cellular mechanism generating ITH in BLCA remains elusive. Here we show that a TM4SF1-positive cancer subpopulation (TPCS) drives ITH diversification in BLCA. By extensive profiling of the epigenome and transcriptome of BLCA from 79 donors across all stages, we elucidated the evolution trajectories of luminal and basal BLCA. TPCS emerges from the basal trajectory and shows extensive transcriptional plasticity with a distinct epigenomic landscape. Clinically, TPCS were enriched in advanced stage patients and associated with poor prognosis. Our results showed how cancer adapts to its environment by adopting a stem cell-like epigenomic landscape.

cancer biology↗

bioRxiv2021

Immunoglobulin-producing AT2-like cells secrete IgA into the extracellular matrix in pulmonary fibrosis

Pulmonary fibrosis is an interstitial lung disease that can be caused by various factors. Here, we first observed extensive IgA deposition in the extracellular matrix (ECM) of the lungs of mice with pulmonary fibrosis induced by silica inhalation. Consistent with this phenomenon, spatial transcriptomic sequencing of fresh mouse lung tissues from control mice and model mice showed that Igha transcripts were highly expressed in the lesion area. Single-cell RNA sequencing (scRNA-seq) and reconstruction of B cell receptor (BCR) sequences revealed a new cluster of cells with a shared BCR and high expression of genes related to immunoglobulin IgA production. Surprisingly, these clonal cells had more characteristics of AT2 (alveolar epithelial cell type 2) cells than B cells; thus, these cells were named AT2-like cells. Therefore, we propose that secretion of IgA into the ECM by AT2-like cells is an important process that occurs during lung fibrosis.

cell biology↗

bioRxiv2021

Causal Haplotype Block Identification in Plant Genome-Wide Association Studies

Genome wide association studies (GWAS) can play an essential role in understanding genetic basis of complex traits in plants and animals. Conventional SNP-based linear mixed models (LMM) used in many GWAS that marginally test single nucleotide polymorphisms (SNPs) have successfully identified many loci with major and minor effects. In plants, the relatively small population size in GWAS and the high genetic diversity found many plant species can impede mapping efforts on complex traits. Here we present a novel haplotype-based trait fine-mapping framework, HapFM, to supplement current GWAS methods. HapFM uses genotype data to partition the genome into haplotype blocks, identifies haplotype clusters within each block, and then performs genome-wide haplotype fine-mapping to infer the causal haplotype blocks of trait. We benchmarked HapFM, GEMMA, BSLMM, and GMMAT in both simulation and real plant GWAS datasets. HapFM consistently resulted in higher mapping power than the other GWAS methods in simulations with high polygenicity. Moreover, it resulted in higher mapping resolution, especially in regions of high LD, by identifying small causal blocks in the larger haplotype block. In the Arabidopsis flowering time (FT10) datasets, HapFM identified four novel loci compared to GEMMAs results, and its average mapping interval of HapFM was 9.6 times smaller than that of GEMMA. In conclusion, HapFM is tailored for plant GWAS to result in high mapping power on complex traits and improved mapping resolution to facilitate crop improvement.

bioinformatics↗

bioRxiv2021

Single-cell Atlas Unveils Cellular Heterogeneity and Novel Markers in Human Neonatal and Adult Intervertebral Discs

The origin, composition, distribution, and function of cells in the human intervertebral disc (IVD) has not been fully understood. Here, cell atlases of both human neonatal and adult IVDs have been generated and further assessed by gene ontology pathway enrichment, pseudo-time trajectory, histology, and immunofluorescence. Comparison of cell atlases revealed the presence of two sub-populations of notochordal cells (NCs) and their associated markers in both the neonatal and adult IVDs. Developmental trajectories predicted 7 different cell states that describe the developmental process from neonatal to adult cells in IVD and analyzed the NCs role in the IVD development. A high heterogeneity and gradual transition of annulus fibrosus cells (AFCs) in the neonatal IVD was detected and their potential relevance in IVD development assessed. Collectively, comparing single-cell atlases between neonatal and adult IVDs delineates the landscape of IVD cell biology and may help discovering novel therapeutic targets for IVD degeneration.

developmental biology↗

bioRxiv2021

Tuning DO:DM ratios modulates MHC class II immunopeptidomes

Major histocompatibility complex class II (MHC-II) antigen presentation underlies a wide range of immune responses in health and disease. However, how MHC-II antigen presentation is regulated by the peptide-loading catalyst HLA-DM (DM), its associated modulator, HLA-DO (DO), is incompletely understood. This is due largely to technical limitations: model antigen presenting cell (APC) systems that express these MHC-II peptidome regulators at physiologically variable levels have not been described. Likewise, computational prediction tools that account for DO and DM activities are not presently available. To address these gaps, we created a panel of single MHC-II allele, HLA-DR4-expressing APC lines that cover a wide range of DO:DM ratio states. Using a combined immunopeptidomic and proteomic discovery strategy, we measured the effects DO:DM ratios have on peptide presentation by surveying over 10,000 unique DR4-presented peptides. The resulting data provide insight into peptide characteristics that influence their presentation with increasing DO:DM ratios. These include DM-sensitivity, peptide abundance, binding affinity and motif, peptide length and register positioning on the source protein. These findings have implications for designing improved HLA-II prediction algorithms and research strategies for dissecting the variety of functions that different APCs serve in the body. IN BRIEFPeptides presented by MHC-II are critical to adaptive immune function. The non-canonical MHC molecules HLA-DM and HLA-DO cooperatively regulate MHC-II function, but how varied DO-to-DM ratios across different APCs and cellular contexts might influence their immunopeptide repertoires is unclear. We address this by measuring cell lines expressing these two proteins spanning a range of relative abundances. We found that peptides could be categorized according to how robustly they were presented at different DO:DM ratios. Importantly, this presentation was only partially linked to predicted affinity to the MHC-II molecule. HIGHLIGHTSO_LIDescribe MHC-class II peptide repertoires from a unique HLA-DR4 cell line panel with increasing DO:DM ratios. C_LIO_LIDemonstrate striking and divergent changes in MHC-II immunopeptidomes that result from the tuning function of DO:DM. C_LIO_LIThese findings bridge gap in understanding and predicting MHC-II antigen presentation. C_LI GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/463141v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@c5038forg.highwire.dtl.DTLVardef@6ce147org.highwire.dtl.DTLVardef@3a32e7org.highwire.dtl.DTLVardef@e3e50a_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2021

Estimating genetic correlation jointly using individual-level and summary-level GWAS data

With the increasing accessibility of individual-level data from genome wide association studies, it is now common for researchers to have individual-level data of some traits in one specific population. For some traits, we can only access public released summary-level data due to privacy and safety concerns. The current methods to estimate genetic correlation can only be applied when the input data type of the two traits of interest is either both individual-level or both summary-level. When researchers have access to individual-level data for one trait and summary-level data for the other, they have to transform the individual-level data to summary-level data first and then apply summary data-based methods to estimate the genetic correlation. This procedure is computationally and statistically inefficient and introduces information loss. We introduce GENJI (Genetic correlation EstimatioN Jointly using Individual-level and summary data), a method that can estimate within-population or transethnic genetic correlation based on individual-level data for one trait and summary-level data for another trait. Through extensive simulations and analyses of real data on within-population and transethnic genetic correlation estimation, we show that GENJI produces more reliable and efficient estimation than summary data-based methods. Besides, when individual-level data are available for both traits, GENJI can achieve comparable performance than individual-level data-based methods. Downstream applications of genetic correlation can benefit from more accurate estimates. In particular, we show that more accurate genetic correlation estimation facilitates the predictability of cross-population polygenic risk scores.

genetics↗