Haplotype-resolved and chromosome-scale genomes provide insights into co-adaptation between the Amur tiger and Amur leopard

DEAR EDITOR,Big cats,such as Amur tigers(Panthera tigris altaica)and Amur leopards(P.pardus orientalis),are apex predator and have evolved specialized traits for hunting and carnivory(Moya et al.,2022),thus playing a crucial role in maintaining biodiversity and ecosystem integrity by regulating prey-predator dynamics.However,human-induced pressures,habitat fragmentation,and environmental alterations have restricted these species in small and isolated populations.Currently,all extant big cats are categorized as endangered or threatened according to their conservation status.Amur tigers and Amur leopards share overlapping geographic ranges,habitats,and certain prey species in the forests of Northeast Asia(Jiang et al.,2015).To reduce interspecies conflict,these carnivores exhibit differentiated dietary and temporal niches.Amur tigers predominantly prey on large ungulates,while Amur leopards hunt small to medium-sized animals(Sugimoto et al.,2016).Additionally,they occupy different temporal niches,with tigers being active at night and leopards more active during the day.Despite spatial and temporal niche partitioning,interspecific competition between these two species is inevitable.Tigers,benefiting from their greater size,have a competitive advantage over leopards,which can manifest in occasional leopard predation by tigers and declines in leopard populations with increasing tiger density(Jiang et al.,2015).Tigers also displace leopards from marginal habitats in nature reserves where they coexist.

Revealing an Invasion Risk of Fish Species in Qingdao Underwater World by Environmental DNA Metabarcoding

Environmental DNA(eDNA)metabarcoding has emerged as a potentially powerful tool to monitor invasive fish species.As an alternative(or complementary)tool for biodiversity monitoring,e DNA metabarcoding had been used to detect species in aquariums,which represents an important transit avenue for introducing non-indigenous species with high population densities.In this study,eDNA metabarcoding as well as morphological characterization were used to reveal the diversity of non-indigenous species in a large aquarium at Qingdao Underwater World.Environmental DNA metabarcoding of 14 water samples at five locations from the Big Water Tank detected 24 non-indigenous species and four putative non-indigenous operational taxonomic units(OTUs).In contrast,only 20 non-indigenous species were observed by morphological characterization.Some species undetected by morphological characterization,such as Oreochromis niloticus(Linnaeus,1758),are highly adaptable to various environments and/or have invaded preferred regions where they threaten native aquatic species.eDNA metabarcoding also detected seven local fishes that were not identified by morphological characterization.However,analysis of OTU diversity among stations and sample replications revealed that eDNA varied within and/or between stations.Increasing sampling effort as well as negative controls are required to increase the detection rate of species and to eliminate false-positive OTUs.

Genome-wide association studies reveal QTL hotspots for grain brightness and black point traits in barley

Grain kernel discoloration(KD)in cereal crops leads to down-grading grain quality and substantial economic losses worldwide.Breeding KD tolerant varieties requires a clear understanding of the genetic basis underlying this trait.Here,we generated a high-density single nucleotide polymorphisms(SNPs)map for a diverse barley germplasm and collected trait data from two independent field trials for five KD related traits:grain brightness(TL),redness(Ta),yellowness(Tb),black point impact(Tbpi),and total black point in percentage(Tbpt).Although grain brightness and black point is genetically correlated,the grain brightness traits(TL,Ta,and Tb)have significantly higher heritability than that of the black point traits(Tbpt and Tbpi),suggesting black point traits may be more susceptible to environmental influence.Using genome-wide association studies(GWAS),we identified a total of 37 quantitative trait loci(QTL),including two major QTL hotspots on chromosomes 4H and 7H,respectively.The two QTL hotspots are associated with all five KD traits.Further genetic linkage and gene transcription analyses identified candidate genes for the grain KD,including several genes in the flavonoid pathway and plant peroxidase.Our study provides valuable insights into the genetic basis for the grain KD in barley and would greatly facilitate future breeding programs for improving grain KD resistance.

Dissecting the genome of star fruit(Averrhoa carambola L.)

Averrhoa carambola is commonly known as star fruit because of its peculiar shape,and its fruit is a rich source of minerals and vitamins.It is also used in traditional medicines in countries such as India,China,the Philippines,and Brazil for treating various ailments,including fever,diarrhea,vomiting,and skin disease.Here,we present the first draft genome of the Oxalidaceae family,with an assembled genome size of 470.51 Mb.In total,24,726 protein-coding genes were identified,and 16,490 genes were annotated using various well-known databases.The phylogenomic analysis confirmed the evolutionary position of the Oxalidaceae family.Based on the gene functional annotations,we also identified enzymes that may be involved in important nutritional pathways in the star fruit genome.Overall,the data from this first sequenced genome in the Oxalidaceae family provide an essential resource for nutritional,medicinal,and cultivational studies of the economically important star-fruit plant.

Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys (Macaca fascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3β,5,6β-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

Author Correction: Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys

Open Access This is an open-access article distributed under the terms of theCreative Commons Attribution Non-Commercial License(http:1/creativecommons.org/licenses/by-nc/4.0/).which permits unrestrictednon-commercial use,distribution.and reproduction in any medium.

Initiation of the Primate Genome Project

A crucial step for understanding human evolution is to identify the genomic changes that occurred during primate evolution,thus allowing investigators to reconstruct the ancestral states preceding the human condition.In the past several decades,the primate clade has been a research focus in genome sequencing due to its unique phylogenetic position and key importance.

A novel mutation in PRPF31,causative of autosomal dominant retinitis pigmentosa,using the BGISEQ-500 sequencer

AIM： To study the genes responsible for retinitis pigmentosa.METHODS： A total of 15 Chinese families with retinitis pigmentosa, containing 94 sporadically afflicted cases, were recruited. The targeted sequences were captured using the Target_Eye_365_V3 chip and sequenced using the BGISEQ-500 sequencer, according to the manufacturer＇s instructions. Data were aligned to UCSC Genome Browser build hg19, using the Burroughs Wheeler Aligner MEM algorithm. Local realignment was performed with the Genome Analysis Toolkit（GATK v.3.3.0） Indel Realigner, and variants were called with the Genome Analysis Toolkit Haplotypecaller, without any use of imputation. Variants were filtered against a panel derived from 1000 Genomes Project, 1000 G_ASN, ESP6500, Ex AC and db SNP138. In all members of Family ONE and Family TWO with available DNA samples, the genetic variant was validated using Sanger sequencing.RESULTS： A novel, pathogenic variant of retinitis pigmentosa, c.357_358 del AA（p.Ser119 Serfs X5） was identified in PRPF31 in 2 of 15 autosomal-dominant retinitis pigmentosa（ADRP） families, as well as in one, sporadic case. Sanger sequencing was performed uponprobands, as well as upon other family members. This novel, pathogenic genotype co-segregated with retinitis pigmentosa phenotype in these two families. CONCLUSION： ADRP is a subtype of retinitis pigmentosa, defined by its genotype, which accounts for 20%-40% of the retinitis pigmentosa patients. Our study thus expands the spectrum of PRPF31 mutations known to occur in ADRP, and provides further demonstration of the applicability of the BGISEQ500 sequencer for genomics research.

Building and sharing medical cohorts for research

Cohort studies are costly and time consuming.They require not only laboratory equipment and assays but also collaboration from participants and health agencies.Due to cost constraints,they are often confined to a specific population.Nevertheless,they play a crucial role in providing fundamental insights for medical advancements,shedding light on the origins of diseases,and acting in socioeconomic influence in policy making.

Standard:Human intestinal organoids

Organoids have attracted great interest for disease modelling,drug discovery and development,and tissue growth and homeostasis investigations.However,lack of standards for quality control has become a prominent obstacle to limit their translation into clinic and other applications.“Human intestinal organoids”is the first guideline on human intestinal organoids in China,jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society:the Chinese Society for Stem Cell Research.This standard specifies terms and definitions,technical requirements,test methods,inspection rules for human intestinal organoids,which is applicable to quality control during the process of manufacturing and testing of human intestinal organoids.It was originally released by the Chinese Society for Cell Biology on 24 September 2022.We hope that the publication of this standard will guide institutional establishment,acceptance and execution of proper practical protocols and accelerate the international standardization of human intestinal organoids for applications.

Standard:Human intestinal cancer organoids

Intestinal cancer is one of the most frequent and lethal types of cancer.Modeling intestinal cancer using organoids has emerged in the last decade.Human intestinal cancer organoids are physiologically relevant in vitro models,which provides an unprecedented opportunity for fundamental and applied research in colorectal cancer.“Human intestinal cancer organoids”is the first set of guidelines on human intestinal organoids in China,jointly drafted and agreed by the experts from the Chinese Society for Cell Biology and its branch society:the Chinese Society for Stem Cell Research.This standard specifies terms and definitions,technical requirements,test methods for human intestinal cancer organoids,which apply to the production and quality control during the process of manufacturing and testing of human intestinal cancer organoids.It was released by the Chinese Society for Cell Biology on 24 September 2022.We hope that the publication of this standard will guide institutional establishment,acceptance and execution of proper practocal protocols,and accelerate the international standardization of human intestinal cancer organoids for clinical development and therapeutic applications.

Comparative study on pattern recognition receptors in non-teleost ray-finned fishes and their evolutionary significance in primitive vertebrates

Pattern recognition receptors(PRRs) play important roles in innate immunity system and trigger the specific pathogen recognition by detecting the pathogen-associated molecular patterns. The main four PRRs components including Toll-like receptors(TLRs), RIG-I-like receptors(RLRs), NOD-like receptors(NLRs) and C-type lectin receptors(CLRs) were surveyed in the five genomes of non-teleost ray-finned fishes(NTR) including bichir(Polypterus senegalus), American paddlefish(Polyodon spathula), alligator gar(Atractosteus spatula), spotted gar(Lepisosteus oculatus) and bowfin(Amia calva), representing all the four major basal groups of ray-finned fishes. The result indicates that all the four PRRs components have been well established in these NTR fishes. In the RLR-MAVS signal pathway, which detects intracellular RNA ligands to induce production of type I interferons(IFNs), the MAVS was lost in bichir particularly. Also, the essential genes of recognition of Lipopolysaccharide(LPS) commonly in mammals like MD2, LY96 and LBP could not be identified in NTR fishes. It is speculated that TLR4 in NTR fishes may act as a cooperator with other PRRs and has a different pathway of recognizing LPS compared with that in mammals. In addition, we provide a survey of NLR and CLR in NTR fishes. The CLRs results suggest that Group V receptors are absent in fishes and Group II and VI receptors are well established in the early vertebrate evolution. Our comprehensive research of PRRs involving NTR fishes provides a new insight into PRR evolution in primitive vertebrate.

Genome-wide detection of additional fetal chromosomal abnormalities by cell-free DNA testing of 15,626 consecutive pregnant women

Cell-free DNA(cfDNA) testing for common fetal trisomies(T21, T18, T13) is highly effective. However, the usefulness of cfDNA testing in detecting other chromosomal abnormalities is unclear. We evaluated the performance of cfDNA testing for genome-wide abnormalities, and analyzed the incremental yield by reporting extra abnormalities. We performed genome-wide cfDNA testing in 15,626 consecutive pregnancies prospectively enrolled in this study. cfDNA testing results were reported and counseling was given depending on the presence of extra chromosomal abnormalities. cfDNA testing identified 190 cases(1.2%)of chromosomal abnormalities including 100 common trisomies and 90 additional abnormalities. By expanding the cfDNA reporting range to genome-wide abnormalities, the false positive rate increased to 0.39%(P<0.001) and positive predictive value(PPV) was reduced to 65.58%(P=0.42). However, the detection yield increased from 0.44% to 0.65%(P=0.014), and cfDNA testing detected 38.61%(39/101) additional abnormalities with no ultrasound and biochemical screening findings. cfDNA testing outperformed biochemical screening by showing 60 times higher true positive rate and fewer false negative results.Genome-wide cfDNA testing significantly increased the diagnostic yield by detecting extra abnormalities, especially those without diagnostic indications. Genome-wide cfDNA testing has fewer false positive and false negative results compared with biochemical screening.

Life History Recorded in the Vagino-cervical Microbiome Along with Multi-omes

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenorrhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

GISAID’s Role in Pandemic Response

GISAID is a global data science initiative and the primary source of genomic and associated metadata of all influenza viruses,Respiratory Syncytial Virus(RSV)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the pandemic coronavirus causing coronavirus disease 2019(COVID-19).GISAID’s publicly accessible data sharing platform enables collaboration of over 42,000 participating researchers from 198 nations and data generators from over 3,500 institutions across the globe.Since the first wholegenome sequences were made available by China CDC through GISAID on January 10.

Integrative Analysis of Genome,3D Genome,and Transcriptome Alterations of Clinical Lung Cancer Samples

Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of cancers.However,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties.To explore the 3D genome structure in clinical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing analysis.We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×10^(4)),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer samples.We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer.By integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene expression.We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures.Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.

Rift Valley Fever Virus and Yellow Fever Virus in Urine: A Potential Source of Infection

Dear Editor,In recent years,the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased.Diseases that were once regional now have the ability to spread globally in a short amount of time and pose a wider threat to public health(Weaver et al.2018).Yellow fever virus(YFV,family Flaviviridae,genus Flavivirus)is a mosquito-borne flavivirus that causes yellow fever in humans and has been endemic in Africa and Latin America for many years(Domingo et al.2018).

Genomic and transcriptomic analysis unveils population evolution and development of pesticide resistance in fall armyworm Spodoptera frugiperda

The fall armyworm(FAW),Spodoptera frugiperda,is a destructive pest native to America and has recently become an invasive insect pest in China.Because of its rapid spread and great risks in China,understanding of FAW genetic background and pesticide resistance is urgent and essential to develop effective management strategies.Here,we assembled a chromosome-level genome of a male FAW(SFynMstLFR)and compared re-sequencing results of the populations from America,Africa,and China.Strain identification of 163 individuals collected from America,Africa and China showed that both C and R strains were found in the American pop-ulations,while only C strain was found in the Chinese and African populations.Moreover,population geno-mics analysis showed that populations from Africa and China have close relationship with significantly genetic differentiation from American populations.Taken toge-ther,FAWs invaded into China were most likely origi-nated from Africa.Comparative genomics analysis displayed that the cytochrome p450 gene family is extremely expanded to 425 members in FAW,of which 283 genes are specific to FAW.Treatments of Chinese populations with twenty-three pesticides showed the variant patterns of transcriptome profiles,and several detoxification genes such as AOX,UGT and GST spe-cially responded to the pesticides.These findings will be useful in developing effective strategies for manage-ment of FAW in China and other invaded areas.

Modes of genetic adaptations underlying functional innovations in the rumen

The rumen is the hallmark organ of ruminants and hosts a diverse ecosystem of microorganisms that facilitates efficient digestion of plant fibers.We analyzed 897 transcriptomes from three Cetartiodactyla lineages:ruminants,camels and cetaceans,as well as data from ruminant comparative genomics and functional assays to explore the genetic basis of rumen functional innovations.We identified genes with relatively high expression in the rumen,of which many appeared to be recruited from other tissues.These genes show functional enrichment in ketone body metabolism,regulation of microbial community,and epithelium absorption,which are the most prominent biological processes involved in rumen innovations.Several modes of genetic change underlying rumen functional innovations were uncovered,including coding mutations,genes newly evolved,and changes of regulatory elements.We validated that the key ketogenesis rate-limiting gene(HMGCS2)with five ruminant-specific mutations was under positive selection and exhibits higher synthesis activity than those of other mammals.Two newly evolved genes(LYZ1 and DEFB1)are resistant to Gram-positive bacteria and thereby may regulate microbial community equilibrium.Furthermore,we confirmed that the changes of regulatory elements accounted for the majority of rumen gene recruitment.These results greatly improve our understanding of rumen evolution and organ evo-devo in general.

CDCP:a visualization and analyzing platform for single-cell datasets

Recently,the rapid advances of single-cell sequencing technologies,including sequencing of single-cell genomics,transcriptomes,epigenetics,and spatial transcriptomes,have empowered researchers to scrutinize cellular heterogeneity,gene expression,epigenetic modifications.