Biology subjects

Zhang, W.

Publications and source records attributed to Zhang, W..

At least 1,027 records · Page 57Linked to original sources

bioRxiv2019

Genotype 1 Japanese encephalitis virus predominates in nature in China

IntroductionJapanese encephalitis virus (JEV), in the genus Flavivirus, family Flaviviridae, is the leading cause of viral encephalitis in the Asian-Pacific region. JEV has a wide range of vector hosts, including mosquitoes, swine, and wading birds. Culex species, especially Culex tritaeniorhynchus, are the main vectors for JEV transmission. JEV has been classified into five genotypes (G1-G5). JEV G1, G3, and G5 isolates have been found in China.\n\nMethodsMore than 200,000 mosquitoes collected in 14 provinces in China from 2004 to 2016 were examined for JEV using a TaqMan real-time RT-PCR assay. The JEV envelope (E) gene was sequenced from positive pools. The nucleic acid sequences were analyzed and aligned using ClustalX ver. 2.0. Representative JEV envelope (E) gene sequences were downloaded from GenBank and compared with the newly obtained JEV sequences. MEGA 5.05 was used to generate a phylogenetic tree based on the JEV sequences.\n\nResultsMore than 200,000 mosquitoes were divided into 3107 pools to test for JEV. Of the pools, 9.04% (281/3107) were positive. The JEV obtained from mosquitoes included three genotypes (G1, G3, and G5). JEV G1 was detected from different provinces during 2004-2016. G1 was the dominant genotype circulating in nature, comprising 98.93% (278/281). JEV G3 was detected in Yunnan and Chongqing Provinces before 2010; JEV G5 was detected only in Tibet. No pools were positive for JEV G2 and G4. C. tritaeniorhynchus was the major mosquito species and the principal vector for transmitting JEV in China. The results of the TaqMan real-time RT-PCR assay and phylogenetic analysis consistently indicated that all 50 newly identified JEV sequences belonged to JEV G1.\n\nConclusionG1 is the main genotype of JEV circulating in nature in China. Some G3 and G5 were found, but no G2 or G4.\n\nAuthor summaryJapanese encephalitis virus (JEV) is a member of the genus Flavivirus, family Flaviviridae and is the major pathogen agent of Japanese encephalitis (JE) in the Asian-Pacific region. The fatality rate of JE is 20-30%. JEV consists of five genotypes (G1-G5). The predominant genotype was G3 before the 20thcentury. G1 and G3 co-circulated in China at the end of the 20thand early 21stcentury. JEV G1 is the youngest genotype and has gradually been found in many areas worldwide. Using a sensitive TaqMan real-time RT-PCR assay, this study examined 3107 pools of mosquito. The main genotype of Japanese encephalitis virus in China was G1, with some G3 and G5, but no G2 or G4. C. tritaeniorhynchus was the major mosquito species and the principal vector for transmitting JEV in China. TaqMan real-time RT-PCR assay and phylogenetic analysis consistently indicated that all 50 newly identified JEV sequences belonged to JEV G1.

molecular biology↗

bioRxiv2019

A multi-omic cohort as a reference point for promoting a healthy human gut microbiome

More than a decade of gut microbiome studies have a common goal for human health. As most of the disease studies sample the elderly or the middle-aged, a reference cohort for young individuals has been lacking. It is also not clear what other omics data need to be measured to better understand the gut microbiome. Here we present high-depth metagenomic shotgun sequencing data for the fecal microbiome together with other omics data in a cohort of 2,183 adults, and observe a number of vitamins, hormones, amino acids and trace elements to correlate with the gut microbiome and cluster with T cell receptors. Associations with physical fitness, sleeping habits and dairy consumption are identified in this large multi-omic cohort. Many of the associations are validated in an additional cohort of 1,404 individuals. Our comprehensive data are poised to advise future study designs to better understand and manage our gut microbiome both in population and in mechanistic investigations.

microbiology↗

bioRxiv2019

3D association of ER, PR and Her2 at protein levels to aid sub-grouping of breast cancer patients in routine clinical practice

Treatments of patients with solid tumors frequently rely on the relative and semi-quantitative assessment of tissue protein biomarkers by immunohistochemistry (IHC). The perspective of transition to absolute and quantitative assessment of tissue biomarkers is hindered by lack of a suitable method, especially for Formalin Fixed Paraffin Embedded (FFPE) tissues. In this study, we explored the feasibility of Quantitative Dot Blot (QDB) method as a universal platform to quantitate tissue biomarkers as absolute and continuous variables in FFPE samples by measuring unprecedentedly the protein levels of Estrogen Receptor (ER), Progesterone Receptor (PR), Her2 and Ki67 simultaneously in 1048 FFPE samples. When using measured Her2, ER and PR levels as coordinates to develop 3D scatterplot, we observed a distinct distribution pattern of the samples with natural segregation of three groups as the likely phenotypical projection of known intrinsic subtypes. Thus, we have achieved a major milestone in this transition by identifying the first practice method for daily clinical practice, and one clinical usage in 3D subtyping of samples for prediction and prognosis. This study may serve as basis for a new field of Quantitative Diagnosis where diagnosis, prognosis and prediction are derived from database analysis of protein biomarkers as absolute and continuous variables.

pathology↗

bioRxiv2019

Live-cell Imaging Analysis of Antimycin-Type Depsipeptides via Bioorthogonal Stimulated Raman Scattering Microscopy

Small-molecule natural products have been an essential source of pharmaceuticals to treat human diseases, but very little is known about their behavior inside dynamic, living human cells. Here, we demonstrate the first structure-activity-distribution study of complex natural products, the anti-cancer antimycin-type depsipeptides, using the emerging bioorthogonal Stimulated Raman Scattering (SRS) Microscopy. Our results show that the intracellular enrichment and distribution of these compounds are driven by their potency and specific protein targets, as well as the lipophilic nature of compounds.

bioengineering↗

bioRxiv2019

Developing a routine lab test for absolute quantification of Her2 in Formalin Fixed Paraffin Embedded (FFPE) breast cancer tissues using Quantitative Dot Blot (QDB) method

While the transition from current prevailing method of relative and semi-quantitative assessment of solid tumor biomarkers to their absolute quantitation promises improved objectivity, consistency and accuracy in daily clinical practice, this transition is hindered by lacking of suitable technique, especially for Formalin Fixed Paraffin Embedded (FFPE) tissue samples. In this retrospective study, Quantitative Dot Blot (QDB) method was adopted to measure Her2 levels absolutely and quantitatively at protein level using 2X15 m FFPE breast cancer tissue slices collected sequentially and non-selectively from local hospital. Her2 levels measured from 332 samples using two diagnostic antibodies respectively were strongly correlated (r=0.963, p=0.0000). When the result was evaluated with results from IHC or FISH analysis using Receiving Operating Characteristics (ROC) analysis, we were able to achieve 100% sensitivity (95% CI: 95.6% to 100%) and 99.3% specificity (95% CI: 96.14% to 99.98%) with results from IHC analysis using 0.267 nmole/g as cutoff, and 93.02% sensitivity (95%CI: 80.94% to 98.54%) and 93.68% specificity (95% CI: 86.76% to 97.65%) with results from FISH analysis using 0.261 nmole/g as cutoff. Thus, QDB method is demonstrated to provide objective and consistent assessment of Her2 levels in FFPE samples with comparable results from both IHC and FISH analyses. It is also the first method to achieve absolute quantitation of tissue biomarkers in FFPE samples to meet daily clinical need.

pathology↗

bioRxiv2019

An ATAC-seq atlas of chromatin accessibility in mouse tissues

The Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) is a fundamental epigenomics approach and has been widely used in profiling the chromatin accessibility dynamics in multiple species. A comprehensive reference of ATAC-seq datasets for mammalian tissues is important for the understanding of regulatory specificity and developmental abnormality caused by genetic or environmental alterations. Here, we report an adult mouse ATAC-seq atlas by producing a total of 66 ATAC-seq profiles from 20 primary tissues of both male and female mice. The ATAC-seq read enrichment, fragment size distribution, and reproducibility between replicates demonstrated the high quality of the full dataset. We identified a total of 296,574 accessible elements, of which 26,916 showed tissue-specific accessibility. Further, we identified key transcription factors specific to distinct tissues and found that the enrichment of each motif reflects the developmental similarities across tissues. In summary, our study provides an important resource on the mouse epigenome and will be of great importance to various scientific disciplines such as development, cell reprogramming, and genetic disease.

genomics↗

bioRxiv2019

MglA functions as a three-state GTPase to control movement reversals of Myxococcus xanthus

In Myxococcus xanthus, directed movement is controlled by inter-dependent pole-to-pole oscillations of the small GTPase MglA, its GAP MglB and the RomR protein. However, these proteins have strikingly different oscillatory regimes such that MglA is segregated from MglB and RomR at reversal activation. The molecular mechanism whereby information is exchanged between the lagging and leading poles resulting in MglA detachment from the leading pole during reversals has remained unknown. Here, we show that MglA has two GTP-bound forms, one of which is insensitive to MglB (MglA-GTP*) and is re-sensitized to MglB by a feedback mechanism operated by MglA-GDP. By identifying the region of MglB that is critical for its association to the lagging pole, we demonstrate that MglA-GTP* is functional in vivo. These data suggest that MglA-GDP acts as a soluble messenger to convert polar MglA-GTP* into a diffusible MglA-GTP species, explaining MglA re-localization to the opposite pole during reversals.

microbiology↗

bioRxiv2019

Pathogen genetic control of transcriptome variation in the Arabidopsis thaliana - Botrytis cinerea pathosystem

Disease symptoms arise from the interaction of the host and pathogen genomes. However, little is known about how genetic variation in the interaction modulates both organisms transcriptomes, especially in complex interactions like those between generalist pathogens and their plant hosts. To begin mapping how polygenic pathogen variation influences both organisms transcriptomes, we used the Botrytis cinerea - Arabidopsis thaliana pathosystem. We measured the co-transcriptome across a genetically diverse collection of 96 B. cinerea isolates infected on the Arabidopsis wildtype, Col-0. Using the B. cinerea genomic variation, we performed genome-wide association (GWA) for each of 23,947 measurable transcripts in the host, and 9,267 measurable transcripts in the pathogen. Unlike other eGWA studies, there was a relative absence of cis-eQTL that is likely explained by structural variants and allelic heterogeneity within the pathogens genome. This analysis identified mostly trans-eQTL in the pathogen with eQTL hotspots dispersed across the pathogen genome that altered the pathogens transcripts, the hosts transcripts, or both the pathogen and the host. Gene membership in the trans-eQTL hotspots suggests links to several known and many novel virulence mechanisms in the plant-pathogen interaction. Genes annotated to these hotspots provide potential targets for blocking manipulation of the host response by this ubiquitous generalist pathogen. This shows that genetic control over the co-transcriptome is polygenic, similar to the virulence outcome in the interaction of Botrytis cinerea on Arabidopsis thaliana.

plant biology↗

bioRxiv2019

Is microbial activity in tropical forests limited by phosphorus availability? Evidence from a tropical forest in China

The prevailing paradigm for soil microbial activity in tropical forests is that microbial activity is limited by phosphorus (P) availability. Thus, exogenous P addition should increase rates of organic matter decomposition. Studies have also confirmed that soil respiration is accelerated when P is added experimentally. However, we hypothesize that the increased rates of soil microbial respiration could be due to the release of organic material from the surface of soil minerals when P is added, because P is more successful at binding to soil particles than organic compounds. In this study, we demonstrate that P addition to soil is associated with significantly higher dissolved organic carbon (DOC) content in a tropical evergreen forest in southern China. Our results indicate that P fertilization stimulated soil respiration but suppressed litter decomposition. Results from a second sorption experiment revealed that the recovery ratio of added DOC in the soil of a plot fertilized with P for 9 years was larger than the ratio in the soil of a non-fertilized plot, although the difference was small. We also conducted a literature review on the effects of P fertilization on the decomposition rates of litter and soil organic matter at our study site. Previous studies have consistently reported that P addition led to higher response ratios of soil microbial respiration than litter decomposition. Therefore, experiments based on P addition cannot be used to test whether microbial activity is P-limited in tropical forest soils, because organic carbon desorption occurs when P is added. Our findings suggest that the prevailing paradigm on the relationship between P and microbial activity in tropical forest soils should be re-evaluated.

ecology↗

bioRxiv2019

Genomic landscape of 261 childhood cancer patient-derived xenograft models

Accelerating cures for children with cancer remains an immediate challenge due to extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs) from high-risk childhood cancers, many refractory to current standard-of-care treatments. Here, we genomically characterize 261 PDX models from 29 unique pediatric cancer malignancies and demonstrate faithful recapitulation of histologies, subtypes, and refine our understanding of relapsed disease. Expression and mutational signatures are used to classify tumors for TP53 and NF1 inactivation, as well as impaired DNA repair. We anticipate that these data will serve as a resource for pediatric oncology drug development and guide rational clinical trial design for children with cancer.\n\nHighlightsO_LIMultiplatform genomic analysis defines landscape of 261 pediatric cancer patient derived xenograft (PDX) models\nC_LIO_LIPediatric patient derived xenografts faithfully recapitulate relapsed disease\nC_LIO_LIInferred TP53 pathway inactivation correlates with pediatric cancer copy number burden\nC_LIO_LISomatic mutational signatures predict impaired DNA repair across multiple histologies\nC_LI

genomics↗

bioRxiv2019

Structural insight into the mechanism of 4-aminoquinolines selectivity for the alpha2A-adrenoceptor

2A-adrenoceptor (AR) is a potential target for the treatment of degenerative diseases of the central nervous system, and 2A-AR agonists are one of the most effective drugs for this condition. However, the lack of high selectivity for 2A-AR subtype of traditional drugs greatly limits their clinic usage. In this study, a series of homobivalent 4-aminoquinolines conjugated by two 4-aminoquinoline moieties via varying alkane linker length (C2-C12) were characterized for their affinities for each 2-AR subtype. Subsequently, docking, molecular dynamics and mutagenesis were applied to uncover the molecular mechanism. Most 4-aminoquinolines (4-aminoquinoline monomer, C2-C6, C8-C10) were selective for the 2A-AR over 2B- and 2C-ARs. Besides, the affinities are of similar linker length-dependence for each 2-AR subtype. Among all the compounds tested, C10 has the highest affinity for the 2A-AR (pKi=-7.45{+/-}0.62), which is 12-fold and 60-fold selective over 2B-AR and 2C-AR, respectively. Docking and molecular dynamics studies suggest that C10 simultaneously interacts with an orthosteric and an "allosteric site" of the 2A-AR. The mutation of F205, which is situated at the orthosteric binding pocket decreases the affinity by 2-fold. The potential allosteric residues include Ser90, Asn93, Glu94 and W99. The specificity of C10 for the 2A-AR and the potential orthosteric and allosteric binding sites proposed in this study provide valuable guidance for the development of novel 2A-AR subtype selective compounds.

pharmacology and toxicology↗

bioRxiv2019

Rapid Detection of Burkholderia pseudomallei with a Lateral Flow Recombinase Polymerase Amplification Assay

Melioidosis is a severe infectious disease caused by gram-negative, facultative intracellular pathogen Burkholderia pseudomallei (B. pseudomallei). Although cases are increasing reported from other parts of the world, it is an illness of tropical and subtropical climates primarily found in southeast Asia and northern Australia. Because of a 40% mortality rate, this life-threatening disease poses a public health risk in endemic area. Early detection of B. pseudomallei infection benefits greatly to implement effective treatment timely, which is vital for prognosis of a melioidosis patient. In this study, a novel isothermal recombinase polymerase amplification combined with lateral flow dipstick (LF-RPA) assay was established for rapid detection of B.pseudomallei. A set of probe and primers targeting orf2 gene of B. pseudomallei were generated and parameters for the LF-RPA assay were optimized. Result can be easy visualized in 30 minutes with the limit of detection (LoD) as low as 20 femtogram (ca. 25.6 copies) of B. pseudomallei genomic DNA. The assay is highly specific as no cross amplification was observed with 35 non-B. pseudomallei pathogens. Isolates (N=19) from patients of Hainan province of China were retrospectively confirmed by the newly developed method. LoD for B. pseudomallei spiked soil and blood samples were 2.1x103 CFU/g and 4.2x103 CFU/ml respectively. Sensitivity of the LF-RPA assay was comparable to TaqMan Real-Time PCR, however, the LF-RPA assay exhibited a better tolerant to inhibitors in blood than the later. Our results showed that the LF-RPA assay is an alternative to existing PCR-based methods for detection of B. pseudomallei with a potentiality of early accurate diagnosis of melioidosis at point of care or in-field use.

microbiology↗

bioRxiv2019

Human defensive freezing is associated with acute threat coping, long term hair cortisol levels and trait anxiety.

The detection and anticipation of threat facilitates innate defensive behaviours including freezing reactions. Freezing in humans is characterized by reductions in body sway and heart rate and limited evidence suggests that individual differences in freezing reactions are associated with hypothalamic-pituitary-adrenal (HPA) axis activity and anxiety. However, previous measurements of human freezing reactions were largely based on passive threat contexts where natural variations in adaptive threat coping could not be assessed. In a well powered sample (N=419), we studied individual differences in anticipatory freezing reactions, by measuring body sway and heart rate, during an active shooting task where shooting decisions had to be taken under threat of shock. We linked freezing measures to subsequent actions and predictors of anxiety-related psychopathology, including accumulated long-term (3 months) hair cortisol concentrations (HCC) and trait anxiety. The anticipation of threat of shock elicited significant body sway- and heart rate reductions consistent with freezing. Whereas both freezing-related reductions in body sway and heart rate were associated with faster correct shooting decisions, body sway reductions were additionally related to more impulsive shooting (false alarms). Individual differences in threat-related reductions in body sway but not heart rate were further associated to lower HCC and higher trait anxiety. The observed links between freezing and subsequent defensive actions as well as predictors of stress-related psychopathology suggest the potential value of defensive freezing reactions as somatic marker for stress-vulnerability and resilience.

physiology↗

bioRxiv2019

Comparative performance of the BGI and Illumina sequencing technology for single-cell RNA-sequencing

The libraries generated by high-throughput single cell RNA-sequencing platforms such as the Chromium from 10X Genomics require considerable amounts of sequencing, typically due to the large number of cells. The ability to use this data to address biological questions is directly impacted by the quality of the sequence data. Here we have compared the performance of the Illumina NextSeq 500 and NovaSeq 6000 against the BGI MGISEQ-2000 platform using identical Single Cell 3 libraries consisting of over 70,000 cells. Our results demonstrate a highly comparable performance between the NovaSeq 6000 and MGISEQ-2000 in sequencing quality, and cell, UMI, and gene detection. However, compared with the NextSeq 500, the MGISEQ-2000 platform performs consistently better, identifying more cells, genes, and UMIs at equalised read depth. We were able to call an additional 1,065,659 SNPs from sequence data generated by the BGI platform, enabling an additional 14% of cells to be assigned to the correct donor from a multiplexed library. However, both the NextSeq 500 and MGISEQ-2000 detected similar frequencies of gRNAs from a pooled CRISPR single cell screen. Our study provides a benchmark for high capacity sequencing platforms applied to high-throughput single cell RNA-seq libraries.

genomics↗

bioRxiv2019

ZEB1 insufficiency causes corneal endothelial cell state transition and altered cellular processing

The zinc finger e-box binding homeobox 1 (ZEB1) transcription factor is a master regulator of the epithelial to mesenchymal transition (EMT), and of the reverse mesenchymal to epithelial transition (MET) processes. ZEB1 plays an integral role in mediating cell state transitions during cell lineage specification, wound healing and disease. EMT/MET are characterized by distinct changes in molecular and cellular phenotype that are generally context-independent. Posterior polymorphous corneal dystrophy (PPCD), associated with ZEB1 insufficiency, provides a new biological context in which to understand and evaluate the classic EMT/MET paradigm. PPCD is characterized by a cadherin-switch and transition to an epithelial-like transcriptomic and cellular phenotype, which we study in a cell-based model of PPCD generated using CRISPR-Cas9-mediated ZEB1 knockout in corneal endothelial cells (CEnCs). Transcriptomic and functional studies support the hypothesis that CEnC undergo a MET-like transition in PPCD, termed endothelial to epithelial transition (EnET), and lead to the conclusion that EnET may be considered a corollary to the classic EMT/MET paradigm.

cell biology↗

bioRxiv2019

Remodeling gut microbiota by Streptococcus thermophilus 19 attenuates inflammation in septic mice

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is the leading cause of death in burn patients. Streptococcus thermophilus 19 is a highly effective probiotic, with well-studied health benefits, but its role in protecting viscera against injury caused by sepsis and the underlying mechanism is poorly understood. The goal of this study was to evaluate protection potency of S. thermophilus against inflammation in mice and evaluate the influence of sepsis and S. thermophilus on microbial community. We tested the utility of S. thermophilus 19 in attenuating inflammation in vitro and vivo of LPS-induced sepsis mouse model. We also evaluated the influence of sepsis and S. thermophilus on microbial community. In vitro, S. thermophilus 19 decrease the expression of inflammatory factors. Additionally, in a lipopolysaccharide-induced septic mouse model, mice administered the probiotic 19 was highly resistant to Lps and exhibited decreased expression of inflammatory factors compared to Lps-treated control mice. A MiSeq-based sequence analysis revealed that gut microbiota alterations in mice intraperitoneally injected with 1 mg/ml LPS were mitigated by the administration of oral probiotics 19. Together these findings indicate that S. thermophilus 19 may be a new avenue for interventions against inflammation caused by sepsis and other systemic inflammatory diseases. In an analysis of the gut microbiota of the all group mice, we found that sepsis is associated with gut microbiota and probiotics attenuate the inflammation through remodeling gut microbiota. ImportanceSepsis is life-threatening organ dysfunction which is the leading cause of death in burn patients. Although our understanding of sepsis has increased substantially in recent years, its still reported to be the leading cause of death in seriously ill patients. Evidences showed that gut microbiota play an important role in sepsis. Moreover, probiotics have been used to prevent numbers of gut health disorders and alleviate inflammation associated with some human diseases by promoting changes in the gut microbiota composition. Hence, to investigate the mechanism of probiotics in the treatment of sepsis has emerged. The significance of our research is in identifying the role of gut microbiota in sepsis and found an effective probiotic that reduces inflammation, S. thermophilus 19, and investigating the therapeutic effect and mechanism of S. thermophilus 19 on sepsis, which might be a new avenue for interventions against inflammation caused by sepsis and other systemic inflammatory diseases.

microbiology↗

bioRxiv2019

The vagino-cervical microbiome as a woman's life history

The gut microbiome has been the center of attention for human commensal microbiome studies. The vaginal microbiome is also densely populated with bacteria, viruses and fungi, and the presence of microorganisms beyond the cervix is increasingly reported in non-infectious conditions1-3. Due to the over 90% of human sequences in female reproductive tract samples3,4, metagenomic information has been very limited. 16S rRNA gene amplicon sequencing studies have identified community types in the vaginal microbiota, and observed its dynamic changes due to menstrual cycles and sexual behaviors in small cohorts5,6. Here we perform metagenomic shotgun sequencing on cervical samples from 516 women of reproductive age (more than 10-fold of the Human Microbiome Project (HMP)4), and dissect major factors, especially pregnancy and delivery histories and contraception methods on the microbiome composition. Features of other body sites, such as mood fluctuations and facial speckles could potentially be deduced from the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota in the female reproductive tract and imply disease susceptibilities that may be relieved by behavioural changes.

microbiology↗

bioRxiv2019

ClinGen Expert Clinical Validity Curation of 164 Hearing Loss Gene-Disease Pairs

PurposeProper interpretation of genomic variants is critical to successful medical decision making based on genetic testing results. A fundamental prerequisite to accurate variant interpretation is the clear understanding of the clinical validity of gene-disease relationships. The Clinical Genome Resource (ClinGen) has developed a semi-quantitative framework to assign clinical validity to gene-disease relationships. MethodsThe ClinGen Hearing Loss Gene Curation Expert Panel (HL GCEP) uses this framework to perform evidence-based curations of genes present on testing panels from 17 clinical laboratories in the Genetic Testing Registry. The HL GCEP curated and reviewed 142 genes and 164 gene-disease pairs, including 105 nonsyndromic and 59 syndromic forms of hearing loss. ResultsThe final outcome included 82 Definitive (50%), 12 Strong (7%), 25 Moderate (15%), 32 Limited (20%), 10 Disputed (6%), and 3 Refuted (2%) classifications. The summary of each curation is date stamped with the HL GCEP approval, is live, and will be kept up-to-date on the ClinGen website (https://search.clinicalgenome.org/kb/gene-validity). ConclusionThis gene curation approach serves to optimize the clinical sensitivity of genetic testing while reducing the rate of uncertain or ambiguous test results caused by the interrogation of genes with insufficient evidence of a disease link.

genomics↗