Biology subjects

Zhang, L.

Publications and source records attributed to Zhang, L..

At least 19 recordsLinked to original sources

bioRxiv2018

Drosophila scribble mutant tumors undergo a transition from a growth arrest state to a proliferative state over time

The Drosophila neoplastic tumor suppressor gene (nTSG) mutant tumors have successfully modeled many aspects of human tumor progression. However, the fly nTSG mutant tumors progress rapidly over days. This is in contrast with most human tumors which develop slowly, harbor heterogeneous cell populations for selection and undergo an evolution-like process. Whether the fast-growing fly nTSG mutant tumors have capacity for evolution remains unclear. Through quantitative analysis of the scrib mutant tumor growth, we found that the scrib mutant tumors evolve to display different growth rates and cell cycle profiles over time. Multiple growth-regulatory signaling pathways show quantitative differences in early versus late scrib mutant tumors. These data suggest that the scrib mutant tumors undergo a transition from a growth arrest state to a proliferative state. Through longitudinal single cell RNA (scRNA) data analysis we found that the scrib mutant tumors harbor heterogeneous cell populations likely of distinct proliferative states, which are available for potential selection. This study raises the possibility of studying tumor evolution in a genetically accessible and fast-growing invertebrate tumor model.

developmental biology↗

bioRxiv2018

INPP5E controls ciliary localization of phospholipids and odor response kinetics in a mouse model of Joubert syndrome

Ciliopathies manifested in part by a dysfunction of several phosphoinositide 5phosphatases constitute Lowes, Dent disease 2 and Joubert syndromes through critical involvement of properly functioning primary cilia (PC). We showed that deletion of INPP5E under the control of OMP-Cre in mature mouse olfactory sensory neurons (OSNs) led to a dramatic redistribution of PI(4,5)P2 (PIP2) in cilia, significant reduction of PI(3,4)P2 and enrichment of PI(3,4,5)P3 in knobs. Redistribution of the phospholipids accompanied marked elongation of cilia in INPP5E-OMP knockout (KO) OSNs. Such a dramatic remodeling of phospholipid composition however did not affect other integral membrane lipids (cholesterol, sphingomyelin, glycosylated phosphaditylinositol, phosphatidylserine). Proteins known to bind with high affinity PIP2 entered the cilia of the KO OSNs. Loss of INPP5E did not affect ciliary localization of endogenous olfactory receptor M71/M72 or distribution and movement of IFT122 particles implicating independent of phospholipids mechanism of retrograde protein transport in cilia of mature OSNs. Net odor sensitivity and response magnitude as measured by EOG was not affected by the mutation. However, odor adaptation in the KO mouse was significantly impaired resulting in less efficient recovery and altered inactivation kinetics of the odor response at the EOG and single-cell level. These findings implicate phosphoinositide-dependent regulation of active Ca2+ extrusion in OSNs whereby controlling the rate of sensory adaptation.\n\nSignificance statementCurrently there are little if any available treatment to cure congenital ciliopathies. This is in part due to lack of basic knowledge of cilia biology. Olfactory cilia as well as primary cilia appear to be a phospholipid privileged organelle distinct from the rest of plasma membrane albeit sharing its continuity. We characterized distribution of several critically important for cell biology phospholipids and showed that their balance, especially of PIP2, is disrupted in Joubert syndrome animal model and has functional implications. Virally assisted delivery of wild type INPP5E to the mutant OSNs was able to restore localization of PIP2 and rescued impaired response to odor.

neuroscience↗

bioRxiv2018

A Simple Approximation To The Bias Of Gene-Environment Interactions In Case/Control Studies With Silent Disease

One of the most important research areas in case-control Genome-Wide Association Studies is to determine how the effect of a genotype varies across the environment or to measure the gene-environment interaction (GxE). We consider the scenario when some of the \"healthy\" controls actually have the disease and when the frequency of these latent cases varies by the environmental variable of interest. In this scenario, performing logistic regression of clinically defined case status on the genetic variant, environmental variable, and their interaction will result in biased estimates of GxE interaction. Here, we derive a general theoretical approximation to the bias in the estimates of the GxE interaction and show, through extensive simulation, that this approximation is accurate in finite samples. Moreover, we apply this approximation to evaluate the bias in the effect estimates of the genetic variants related to mitochondrial proteins a large-scale Prostate Cancer study.

genetics↗

bioRxiv2018

A simple approximation to bias in gene-environment interaction estimates when a case might not be the case

Case-control genetic association studies are often used to examine the role of the genetic basis in complex diseases, such as cancer and neurodegenerative diseases. The role of the genetic basis might vary by non-genetic (environmental) measures, what is traditionally defined as gene-environment interactions (GxE). A commonly overlooked complication is that the set of clinically diagnosed cases might be contaminated by a subset with a nuisance pathologic state that presents with the same symptoms as the pathologic state of interest. The genetic basis of the pathologic state of interest might differ from that of the nuisance pathologic state. Often frequencies of the pathologically defined states within the clinically diagnosed set of cases vary by the environment. We derive a simple and general approximation to bias in GxE parameter estimates when presence of the nuisance pathologic state is ignored. We then perform extensive simulation studies to show that ignoring presence of the nuisance pathologic state can result in substantial bias in GxE estimates and that the approximation we derived is reasonably accurate in finite samples. We demonstrate the applicability of the proposed approximation in a study of Alzheimers disease.

genetics↗

bioRxiv2018

KPNA2 promotes cellular proliferation and inhibits apoptosis in the Saos-2 osteosarcoma cell line

Karyopherin 2 plays a critical role in tumorigenesis and tumor progression. However, nothing is currently known about the effects of KPNA2 on osteosarcomas. This study aimed to investigate differential KPNA2 protein and mRNA expression in human osteosarcoma tumor cells and normal bone tissue. We also sought to determine whether KPNA2 can influence the proliferation and apoptosis of the Saos-2 osteosarcoma cell line. Immunohistochemistry (IHC) was used to investigate KPNA2 protein expression. Real-time quantitative PCR (qPCR) was used to detect levels of KPNA2 mRNA expression, and lentivirus-mediated short-hairpin RNAs (shRNAs) were used to knock down KPNA2 expression in Saos-2 cells. The MTT assay and multiparametric high-content screening (HCS) were used to measure cell proliferation and growth, respectively. Flow cytometry was conducted to detect cell cycle distribution and apoptosis. The results revealed significantly higher KPNA2 expression levels in osteosarcoma tissues than in normal bone tissues; furthermore, KPNA2 mRNA was also highly expressed in three osteosarcoma cell lines. After transducing Saos-2 cells with KPNA2-shRNA lentivirus, the proliferative rate was notably decreased compared to that of the negative control (NC) lentivirus group (P<0.05). Flow cytometry results indicated that KPNA2 may arrest cell cycle progression and regulate the growth of these cells. The results for apoptosis indicated an apoptotic rate of 13.38{+/-}0.48% in KPNA2-shRNA cells, which was significantly higher than the rate for cells in the control group (5.13 {+/-}0.33%). Therefore, this study showed that KPNA2 is highly expressed in osteosarcoma tissues and that reduced KPNA2mRNA levels inhibited proliferation and promoted apoptosis in an osteosarcoma cell line.

cancer biology↗

bioRxiv2018

Proteomic Profile of TGF-β1 treated Lung Fibroblasts identifies Novel Markers of Activated Fibroblasts in the Silica Exposed Rat Lung

We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) on control and TGF-{beta}1-exposed rat lung fibroblasts to identify proteins differentially expressed between cell populations. A total of 1648 proteins were found to be differentially expressed in response to TGF-{beta}1 treatment and 196 proteins were expressed at [≥] 1.2 fold relative to control. Guided by these results, we next determined whether similar changes in protein expression were detectable in the rat lung after chronic exposure to silica dust. Of the five proteins selected for further analysis, we found that levels of all proteins were markedly increased in the silica-exposed rat lung, including the proteins for the very low density lipoprotein receptor (VLDLR) and the transmembrane (type I) heparin sulfate proteoglycan called syndecan 2 (SDC2). Because VLDLR and SDC2 have not, to our knowledge, been previously linked to the pathobiology of silicosis, we next examined whether knockdown of either gene altered responses to TGF-{beta}1 in MRC-5 lung fibroblasts. Interestingly, we found knockdown of either VLDLR or SDC2 dramatically reduced collagen production to TGF-{beta}1, suggesting that both proteins might play a novel role in myofibroblast biology and pathogenesis of silica-induced pulmonary fibrosis. In summary, our findings suggest that performing LC-MS/MS on TGF-{beta}1 stimulated lung fibroblasts can uncover novel molecular targets of activated myofibroblasts in silica-exposed lung.\n\nHighlightsWe identified 196 proteins differentially expressed between control and TGF-{beta}1 treated fibroblastsby LC-MS/MS.\n\nSeveral proteins identified by LC-MS/MS were also found to be differentially expressed in whole lung tissues and isolated fibroblasts after chronic exposure to silica dust, including the very low density lipoprotein receptor (VLDLR) and the transmembrane type I heparan sulfate proteoglycan called syndecan 2\n\nKnockdown of SDC2 or VLDLR markedly inhibited collagen production in MRC-5 fibroblasts, suggesting a novel pathogenic role for these proteins in myofibroblast biology.

pharmacology and toxicology↗

bioRxiv2018

Conserved mechanism of nucleoporin regulation of the Kcnq1ot1 imprinted domain with divergence in embryonic and trophoblast stem cells

Genomic imprinting is an epigenetic phenomenon, whereby dual chromatin states lead to expression of one, and silencing of the other parental allele. Recently, we identified a nucleoporin-mediated mechanism of Kcnq1ot1 imprinted domain regulation in extraembryonic endoderm stem cells by nucleoporins NUP107, NUP62 and NUP153. Here, we investigate their role in Kcnq1ot1 imprinted domain regulation in embryonic and trophoblast stem cells. Nucleoporin depletion in both lineages reduced Kcnq1ot1 noncoding RNA expression and volume, reduced Kcnq1ot1 paternal domain positioning at the nuclear periphery, and altered histone modifications along with histone modifier enrichment at the imprinting control region. However, while CTCF and cohesin were enriched at nucleoporin binding sites in the imprinting control region in embryonic stem cells, with reduction upon nucleoporin depletion, neither CTCF or cohesin occupied these sites in trophoblast stem cells. Finally, different subsets of silent paternal alleles were reactivated via altered histone modification upon nucleoporin depletion in embryonic and trophoblast stem cells. These results demonstrate a conserved mechanism with divergent regulation of the Kcnq1ot1 imprinted domain by NUP107, NUP62 and NUP153 in embryonic and extraembryonic lineages.\n\nSummary StatementInvestigation of nucleoporins, NUP107, NUP62, and NUP153, revealed a conserved nucleoporin-dependent mechanism that mediates Kcnq1ot1 imprinted domain regulation in ES and TS cells, although notable lineage-specific divergence was also observed.

genetics↗

bioRxiv2018

Atypically larger variability of resource allocation accounts for visual working memory deficits in schizophrenia

Schizophrenia patients are known to have profound deficits in visual working memory (VWM), and almost all previous studies attribute the deficits to decreased memory capacity. This account, however, ignores the potential contributions of other VWM components (e.g., memory precision). Here, we measure the VWM performance of schizophrenia patients and healthy control subjects on two classical delay-estimation tasks. Moreover, we thoroughly evaluate several established computational models of VWM to compare the performance of the two groups. We find that the model assuming variable precision across items and trials is the best model to explain the performance of both groups. According to the variable-precision model, schizophrenia subjects exhibit abnormally larger variability of allocating memory resources rather than resources per se. These results invite a rethink of the widely accepted decreased-capacity theory and propose a new perspective on the diagnosis and rehabilitation of schizophrenia.

neuroscience↗

bioRxiv2018

Exploring the Binding Mechanism between Human Profilin (PFN1) and Polyproline-10 through Binding Mode Screening

The large magnitude of protein-protein interaction (PPI) pairs within the human interactome necessitates the development of predictive models and screening tools to better understand this fundamental molecular communication. However, despite enormous efforts from various groups to develop predictive techniques in the last decade, PPI complex structures are in general still very challenging to predict due to the large number of degrees of freedom. In this study, we use the binding complex of human profilin (PFN1) and polyproline-10 (P10) as a model system to examine various approaches, with the aim of going beyond normal protein docking for PPI prediction and evaluation. The potential of mean force (PMF) was first obtained from the timeconsuming umbrella sampling, which confirmed that the most stable binding structure identified by the maximal PMF difference is indeed the crystallographic binding structure. Moreover, crucial residues previously identified in experimental studies, W3, H133 and S137 of PFN1, were found to form favorable hydrogen bonds with P10, suggesting a zipping process during the binding between PFN1 and P10. We then explored both regular molecular dynamics (MD) and steered molecular dynamics (SMD) simulations, seeking for better criteria of ranking the PPI prediction. Despite valuable information obtained from conventional MD simulations, neither the commonly used interaction energy between the two binding parties nor the long-term root mean square displacement (RMSD) correlates well with the PMF results. On the other hand, with a sizable collection of trajectories, we demonstrated that the average rupture work calculated from SMD simulations correlates fairly well with the PMFs (R2 = 0.67), making it a promising PPI screening method.

biophysics↗

bioRxiv2018

Altered Bacteria-Fungi Inter-Kingdom Network in Gut of Ankylosing Spondylitis Patients

Intestinal bacterial dysbiosis has been increasingly linked to Ankylosing Spondylitis (AS), which is a prototypic and best studied subtype of Spondyloarthritis (SpA). Fungi and bacteria coexist in human gut and interact with each other, although they have been shown to contribute actively to health or diseases, no studies have investigated whether fungal microbiota in AS patients is perturbed. In this study, fecal samples of 22 AS patients, with clinical and radiographic assessments, and 16 healthy controls (HCs) were collected to systematically characterize the gut microbiota and mycobiota in AS patients by 16S rDNA and ITS2-based DNA sequencing. The relationships between therapeutic regimens, disease activity, radiographic damage of AS and gut micro/mycobiome were investigated. Our results showed a distinct mycobiota pattern in AS in addition to microbiota dysbiosis. The gut mycobiome of AS patients was characterized by higher taxonomic levels of Ascomycota, especially the class of Dothideomycetes, and decreased abundance of Basidiomycota, which was mainly contributed by the decease of Agaricales. Compared to HCs, changing of the ITS2/16S biodiversity ratio, and bacteria-fungi interkingdom network were observed in AS patients. Alteration of gut mycobiota was associated with different therapeutic regimens, disease activity, as well as different degrees of radiographic damage. Moreover, we unraveled a disease-specific interkingdom network alteration in AS. Finally, we also identified some trends suggesting that different therapeutic regimens may induce changing of both bacterial and fungal microbiota in AS.\n\nIMPORTANCEHuman gut is colonized by diverse fungi (mycobiome), and they have long been suspected in the pathogenesis of Spondyloarthritis (SpA). Our study unraveled a disease-specific interkingdom network alteration in AS, suggesting that fungi, or the interkingdom interactions between bacteria and fungi, may play an essential role in AS development. However, limited by sample size and indeep mechanism studies, further large scale investigations on the characterization of gut mycobiome in AS patients are needed to form a foundation for research into the relationship between mycobiota dysbiosis and AS development.

microbiology↗

bioRxiv2018

Cyclin B3 is specifically required for metaphase to anaphase transition in mouse oocyte meiosis I

Meiosis, a cell division to generate gametes for sexual reproduction in eukaryotes, executes a single round of DNA replication and two successive rounds of chromosome segregation [1]. The extraordinary reliability of the meiotic cycle requires the activities of cyclin-dependent kinases (Cdks) associated with specific cyclins [2-4]. Cyclins are the regulatory subunits of protein kinases, which are the main regulators of maturation promoting factor or mitosis promoting factor (MPF) [5, 6] and anaphase-promoting complex/cyclosome (APC/C) [7, 8] in eukaryotic cell division. But how cyclins collaborate to control meiosis is still largely unknown. Cyclin B3 (Ccnb3) shares homology with A- and B-type cyclins [9], and is conserved during higher eukaryote evolution [10-17]. Previous studies have shown that Ccnb3-deleted females are sterile with oocytes unable to complete meiosis I in Drosophila [18], implying that Ccnb3 may have a special role in meiosis. To clarify the function of Ccnb3 in meiosis in mammalian species, we generated Ccnb3 mutant mice by CRISPR/Cas9, and found that Ccnb3 mutation caused female infertility with the failure of metaphase-anaphase transition in meiosis I. Ccnb3 was necessary for APC/C activation to initiate anaphase I, but not required for oocytes maturation, meiosis II progression, or early embryonic development. Our study reveals the differential cell cycle regulation between meiosis I and meiosis II, as well as meiosis between males and females, which shed light on the cell cycle control of meiosis.\n\nHighlightsO_LIIdentification of a female meiosis-specific cyclin in mouse\nC_LIO_LICyclin B3 is required for metaphase-anaphase transition in oocyte meiosis I\nC_LIO_LICyclin B3 is not essential for oocyte maturation and sister chromosome segregation\nC_LIO_LICyclin B3 is necessary for APC/C activation and MPF kinase activity through Cdk1\nC_LI

cell biology↗

bioRxiv2018

IDH1R132H acts as a tumor suppressor in glioma via epigenetic upregulation of the DNA damage response

One sentence summaryMutant IDH1 acts as a tumor suppressor when co-expressed together with TP53 and ATRX inactivating mutations in glioma, inducing genomic stability, DNA repair and resistance to genotoxic therapies.\n\nAbstractGlioma patients whose tumors carry a mutation in the Isocitrate Dehydrogenase 1 (IDH1R132H) gene are younger at the time of diagnosis and survive longer. The molecular glioma subtype which we modelled, harbors IDH1R132H, tumor protein 53 (TP53) and alpha-thalassemia/mental retardation syndrome X-linked (ATRX) loss. The impact of IDH1R132H on genomic stability, DNA damage response (DDR) and DNA repair in this molecular glioma subtype is unknown. We discovered that IDH1R132H expression in the genetic context of ATRX and TP53 inactivation: (i) increases median survival (MS), (ii) enhances DDR activity via epigenetic upregulation of Ataxia-telangiectasia mutated (ATM) signaling, and (iii) elicits tumor radioresistance. Pharmacological inhibition of ATM or checkpoint kinase 1 and 2 (CHK1/2), two essential kinases in the DDR pathways, restored tumors radiosensitivity. Translation of these findings for mlDH1 glioma patients could significantly improve the therapeutic efficacy of radiotherapy, and thus have a major impact on patient survival.

cancer biology↗

bioRxiv2018

Dysregulation of EMT Drives the Progression to Clinically Aggressive Sarcomatoid Bladder Cancer

The sarcomatoid variant of urothelial bladder cancer (SARC) displays a high propensity for distant metastasis and is associated with short survival. We report a comprehensive genomic analysis of 28 cases of SARCs and 84 cases of conventional urothelial carcinomas (UCs), with the TCGA cohort of 408 muscle-invasive bladder cancers serving as the reference. SARCs showed a distinct mutational landscape with enrichment of TP53, RB1, and PIK3CA mutations. They were related to the basal molecular subtype of conventional UCs and could be divided into epithelial/basal and more clinically aggressive mesenchymal subsets based on TP63 and its target genes expression levels. Other analyses revealed that SARCs are driven by downregulation of homotypic adherence genes and dysregulation of cell cycle and EMT networks, and nearly half exhibited a heavily infiltrated immune phenotype. Our observations have important implications for prognostication and the development of more effective therapies for this highly lethal variant of bladder cancer.

genomics↗

bioRxiv2018

Exogenous DCPTA ameliorates the soil drought effect on nitrogen metabolism in maize during the pre-female inflorescence emergence stage

Abstract2-(3,4-Dichlorophenoxy) triethylamine (DCPTA) regulates many aspects of plant development; however, its effects on soil drought tolerance are unknown. We pre-treated maize (Zea mays L.) by foliar application of DCPTA and subsequently exposed the plants to soil drought and rewatering conditions during the pre-female inflorescence emergence stage. Exogenous DCPTA significantly alleviated drought-induced decreases in maize yield, shoot and root relative growth rate (RGR), leaf relative water content (RLWC), net photosynthetic rate (Pn), stomatal conductance (Gs) and transpiration rate (Tr), nitrate (NO3-), nitrite (NO2-), and soluble protein contents, and nitrate reductase (NR), nitrite reductase (NiR), isocitrate dehydrogenase (ICDH), alanine aminotransferase (AlaAT) and aspartate aminotransferase (AspAT) activities; increases in the intercellular CO2 concentration (Ci), the ammonium (NH4+) and free amino acid contents, and the glutamate dehydrogenase (GDH) and protease activities. Simultaneously, exogenous DCPTA improved the spatial and temporal distribution of roots and increased the root hydraulic conductivity (Lp), flow rate of root-bleeding sap and NO3- delivery rates. Moreover, Exogenous DCPTA protected the chloroplast structure from drought injury. Taken together, our results suggest that exogenous DCPTA mitigates the repressive effects of drought on N metabolism and subsequently enhances drought tolerance during the pre-female inflorescence emergence stage of maize.\n\nHighlightsThis is the first article that explores the effects of DCPTA on nitrogen metabolism and the first article that explores the effects of DCPTA on crops under soil drought conditions.

physiology↗

bioRxiv2018

PBLR: an accurate single cell RNA-seq data imputation tool considering cell heterogeneity and prior expression level of dropouts

Single-cell RNA sequencing (scRNA-seq) provides a powerful tool to determine precise expression patterns of tens of thousands of individual cells, decipher cell heterogeneity and cell subpopulations and so on. However, scRNA-seq data analysis remains challenging due to various technical noise, e.g., the presence of dropout events (i.e., excess zero counts). Taking account of cell heterogeneity and structural effect of expression on dropout rate, we propose a novel method named PBLR to accurately impute the dropouts of scRNA-seq data. PBLR is an effective tool to recover dropout events on both simulated and real scRNA-seq datasets, and can dramatically improve low-dimensional representation and recovery of gene-gene relationship masked by dropout events compared to several state-of-the-art methods. Moreover, PBLR also detect accurate and robust cell subpopulations automatically, shedding light its flexibility and generality for scRNA-seq data analysis.

bioinformatics↗

bioRxiv2018

Expression profile analysis of circular RNAs in essential hypertension by microarray and bioinformatics.

Circular RNAs (circRNAs), widely found in human cells, are involved in disease and play an important role in progression. To determine whether circRNAs are related in essential hypertension (EH), we analyzed the expression profile of circRNAs and miRNAs in 5 EH and 5 healthy controls cases which were screened by microarray. Through microarray data and public data analysis, differently expressed transcripts were divided into modules, and circRNAs were functionally annotated by miRNAs. The expression of two circRNAs, has_circ_0037909 and has_circ_0105015, were validated in EH by qRT-PCR, which may be associated with EH. Further analysis showed that two circRNAs might through immune system by up-regulation circRNAs and down-regulation expression. These circRNAs biological functions need to be further validated.

genetics↗

bioRxiv2018

A comprehensive ensemble model for comparing the allosteric effect of ordered and disordered proteins

Intrinsically disordered proteins/regions (IDPs/IDRs) are prevalent in allosteric regulation. It was previously thought that intrinsic disorder is favorable for maximizing the allosteric coupling. Here, we propose a comprehensive ensemble model to compare the roles of both order-order transition and order-disorder transition in allosteric effect. It is revealed that the MWC pathway (order-order transition) has a higher probability than the EAM pathway (disorder-order transition) in allostery, suggesting a complicated role of IDPs/IDRs in regulatory proteins. In addition, an analytic formula for the maximal allosteric coupling response is obtained, which shows that too stable or too unstable state is unfavorable to endow allostery, and is thus helpful for rational design of allosteric drugs.\n\nAuthor SummaryAllosteric effect is an important regulation mechanism in biological processes, where the binding of a ligand at one site of a protein influences the function of a distinct site. Conventionally, allostery was thought to originate from structural transition. However, in recent years, intrinsically disordered proteins (IDPs) were found to be widely involved in allosteric regulation in despite of their lack of ordered structure under physiological condition. It is still a mystery why IDPs are prevalent in allosteric proteins and how they differ from ordered proteins in allostery. Here, we propose a comprehensive ensemble model which includes both ordered and disordered states of a two-domain protein, and investigate the role of various state combinations in allosteric effect. By sampling the parameter space, we conclude that disordered proteins are less competitive than ordered proteins in performing allostery from a thermodynamic point of view. The prevalence of IDPs in allosteric regulation is likely determined by all their advantage, but not only by their capacity in endowing allostery.

biophysics↗

bioRxiv2018

Inference of Chromosome-length Haplotypes Using Genomic Data of Three to Five Single Gametes

Knowledge of chromosome-length haplotypes will not only advance our understanding of the relationship between DNA and phenotypes, but also promote a variety of genetic applications. Here we present Hapi, an innovative method for chromosomal haplotype inference using only 3 to 5 gametes. Hapi outperformed all existing haploid-based phasing methods in terms of accuracy, reliability, and cost efficiency in both simulated and real gamete datasets. This highly cost-effective phasing method will make large-scale haplotype studies feasible to facilitate human disease studies and plant/animal breeding. In addition, Hapi can detect meiotic crossovers in gametes, which has promise in the diagnosis of abnormal recombination activity in human reproductive cells.

bioinformatics↗