Increased RNA editing sites revealed as potential novel biomarkers for diagnosis in primary Sjögren's syndrome.

BACKGROUND: Transcriptome-wide aberrant RNA editing has been shown to contribute to autoimmune diseases, but its extent and significance in primary Sjögren's syndrome (pSS) are currently poorly understood. METHODS: We systematically characterized the global pattern and clinical relevance of RNA editing in pSS by performing large-scale RNA sequencing of minor salivary gland tissues obtained from 439 pSS patients and 130 non-pSS or healthy controls. FINDINGS: Compared with controls, pSS patients displayed increased global RNA-editing levels, which were significantly correlated and clinically relevant to various immune features in pSS. The elevated editing levels were likely explained by significantly increased expression of adenosine deaminase acting on RNA 1 (ADAR1) p150 in pSS, which was associated with disease features. In addition, genome-wide differential RNA editing (DRE) analysis between pSS and non-pSS showed that most (249/284) DRE sites were hyper-edited in pSS, especially the top 10 DRE sites dominated by hyper-edited sites and assigned to nine unique genes involved in the inflammatory response or immune system. Interestingly, among all DRE sites, six RNA editing sites were only detected in pSS and resided in three unique genes (NLRC5, IKZF3 and JAK3). Furthermore, these six specific DRE sites with significant clinical relevance in pSS showed a strong capacity to distinguish between pSS and non-pSS, reflecting powerful diagnostic efficacy and accuracy. CONCLUSION: These findings reveal the potential role of RNA editing in contributing to the risk of pSS and further highlight the important prognostic value and diagnostic potential of RNA editing in pSS.

Effect of Al2Cu constituent layer thickness discrepancy on the tensile mechanical behavior of Cu/Al2Cu/Al layered composites: a molecular dynamics simulation.

Nano-polycrystalline Cu/Al2Cu/Al layered composites with different layer thicknessesdof single-crystal Al2Cu constituent are constructed. The effects ofdon the strength and fracture modes of nano-polycrystalline Cu/Al2Cu/Al layered composites are systematically investigated by molecular dynamics simulations. The uniaxial tensile results show that the ultimate strength and fracture mode of the nano-polycrystalline Cu/Al2Cu/Al layered composites do not change monotonically with the change of single crystal Al2Cu constituent layer thicknessd, the ultimate strength peaking atd= 2.44 nm, and the toughness reaching the optimum atd= 4.88 nm. The improvement of deformation incompatibility between Cu, Al and Al2Cu components increases the ultimate strength of polycrystalline Cu/Al2Cu/Al laminated composites. Due to the high activity of Cu dislocation and the uniformity of strain distribution of single crystal Al2Cu, the fracture of nano-crystalline Cu/Al2Cu/Al layered composites changes from brittleness to toughness. This study is crucial to establish the organic connection between microstructure and macroscopic properties of Cu/Al layered composites. To provide theoretical basis and technical support for the application of Cu/Al layered composites in high-end fields, such as automotive and marine, aerospace and defense industries.

Seroprevalence of neutralizing antibodies against the respiratory syncytial virus in healthy adults in Guangzhou, southern China.

Respiratory syncytial virus (RSV) is the major cause of pneumonia and bronchiolitis in infants and young children and mediates substantial morbidity and mortality in the elderly and immunocompromised globally. The development of a safe and effective RSV vaccine and an optimized neutralizing antibody (NAb) with strong virus-neutralizing activity is appealing. To gain some detailed knowledge of the humoral immune response to RSV subgroup A (RSV-A) and RSV-B, we investigated the seroprevalence of pre-existing NAbs by using the microneutralization assay in healthy adult from Guangzhou, southern China. We found that the overall seropositive rate was 84.86% for anti-RSV NAbs. Furthermore, the seropositive rates were 68.47% and 73.61% for anti-RSV-A NAbs and anti-RSV-B NAbs, respectively. In addition, although the seropositive rates and NAb levels were not associated with the blood type, type AB individuals displayed higher seropositive rates for anti-RSV-A NAbs with high titer (≥ 288) and anti-RSV-B NAbs, especially those with moderate titer (≥ 72 to < 288). The seropositive rates and titers were comparable between anti-RSV-A NAbs and anti-RSV-B NAbs in the AB blood type group. Interestingly, only when the NAb titer of the serum to RSV-A was not less than 288, was it not less than 18 to RSV-B, and vice versa. These results would be helpful for a better understanding of the human serum NAb responses to RSV-A and RSV-B.

Rhodohalobacter mucosus sp. nov., isolated from a marine solar saltern.

A Gram-stain-negative, non-motile, aerobic, rod-shaped and reddish-pigmented bacterium, designated 8A47T, was isolated from a marine solar saltern located in Wendeng, PR China. The novel strain 8A47T grows at 20-42 °C, pH 7.0-9.0, and in the presence of 2.0-14.0% (w/v) NaCl. Optimal growth was observed at 37-40 °C, pH 7.5-8.0, and with 4.0-6.0% (w/v) NaCl. The phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 8A47T formed an evolutionary lineage with members of the genus Rhodohalobacter. Strain 8A47T exhibited high level of similarity to Rhodohalobacter barlenses MCCC 1K03442T (94.7%) and Rhodohalobacter halophilus JZ3C29T (93.5%). The major fatty acids were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0 and iso-C15:0. The sole respiratory quinone was MK-7. The polar lipids of the new isolate consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified lipid, two unidentified phospholipids and three unidentified glycolipids and. The genomic DNA G + C content of the strain 8A47T was 47.7 mol%. Based on its phenotypic, chemotaxonomic, genotypic and genomic characteristics presented in this study, strain 8A47T is considered to represent a novel species of the genus Rhodohalobacter, for which the name Rhodohalobacter mucosus sp. nov. is proposed. The type strain is 8A47T (= KCTC 62603T = MCCC 1H00329T).

Distinct genetic patterns of shared and unique genes across four neurodevelopmental disorders.

Neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual disability (ID), developmental disorders (DD) and epileptic encephalopathy (EE), have a strong clinical comorbidity, which indicates a common genetic etiology across various disorders. However, the underlying genetic mechanisms of comorbidity and specificity remain unknown across neurodevelopmental disorders. Based on de novo mutations, we compared systematically the functional characteristics between shared and unique genes under these disorders, as well as the spatiotemporal trajectory of development in brain and common molecular pathways of all shared genes. We observed that shared genes present more constrained against functional rare genetic variation, and harbor more pathogenic rare variants than do unique genes in each disorder. Furthermore, 71 shared genes formed two clusters related to synaptic transmission, transcription regulation and chromatin regulator. Particularly, we also found that two core genes STXBP1 and SCN2A, that were shared by the four neurodevelopmental disorders showed prominent pleiotropy. Our findings shed light on the shared and specific patterns across neurodevelopmental disorders and will enable us to further comprehend the etiology and provide valuable information for the diagnosis of neurodevelopmental disorders.

Nonrandom occurrence of multiple de novo coding variants in a proband indicates the existence of an oligogenic model in autism.

PURPOSE: Elucidating the genetic architecture underlying autism spectrum disorder (ASD) will aid in the understanding of its genetic etiology and clinical diagnosis. METHODS: A comprehensive set of coding de novo variants (DNVs) from 4504 trios with ASD and 3012 control/sibling trios from several large-scale sequencing studies were collected and combined. Multiple in-depth analyses including DNVs burden, clinical phenotypes, and functional networks underlying the combined data set were used to evaluate the nonrandom occurrence of multiple extreme DNVs (loss-of-function and damaging missense variants) in the same patients. RESULTS: We observed a significant excess of multiple extreme DNVs among patients with ASD compared with controls. Meanwhile, patients with ASD carrying 2+ extreme DNVs had significantly lower IQs than patients carrying 0 or 1 DNV. Moreover, much closer functional connectivity than expected was observed among 2 or more genes with extreme DNVs from the same individuals. In particular, we identified 56 key genes as more confident ASD genes compared with other known ASD genes. In addition, we detected 23 new ASD candidate genes with recurrent DNVs, including VIP, ZWILCH, MSL2, LRRC4, and CAPRIN1. CONCLUSIONS: Our findings present compelling statistical evidence supporting an oligogenic model and provide new insights into the genetic architecture of ASD.

Circular RNA sequencing indicates circ-IQGAP2 and circ-ZC3H6 as noninvasive biomarkers of primary Sjögren's syndrome.

OBJECTIVES: This study aims to characterize the expression profiles of circRNAs in primary Sjogren's Syndrome (pSS) and examine the potential of noninvasive circular RNAs (circRNAs) as biomarkers of pSS. METHODS: We performed RNA sequencing of minor salivary gland (MSG) biopsies from four pSS and four non-pSS individuals (subjects undergoing MSG biopsies but not meeting 2012 or 2016 ACR classification criteria for SS). Differentially expressed circRNAs were identified by DESeq2, and confirmed by quantitative real-time PCR in the MSGs as well as in plasma exosomes in 37 pSS and 14 non-pSS subjects. Discriminatory capacity testing using receiver operating characteristic analysis was used to evaluate the performance of circRNAs as diagnostic biomarkers for pSS. RESULTS: Circ-IQGAP2 and circ-ZC3H6 had significantly upregulated expression in the MSGs of pSS patients, and this elevated expression was confirmed by quantitative real-time PCR of plasma exosome RNA. The expression of these circRNAs also showed significant correlation with both clinical features, serum IgG level and MSG focus scores. Receiver operating characteristic analysis showed that the indices comprised of both the two circRNAs and clinical features were better able to distinguish pSS from non-pSS subjects with high mean areas under the curve of 0.93 in the MSGs and 0.92 in the plasma exosomes. CONCLUSION: This study indicated the potential roles of circ-IQGAP2 and circ-ZC3H6 as noninvasive biomarkers for the diagnosis of pSS.

The angiotensin-converting enzyme 2/angiotensin (1-7)/mas axis protects against pyroptosis in LPS-induced lung injury by inhibiting NLRP3 activation.

Previous studies have suggested that pyroptosis may play an important role in LPS-induced acute lung injury (ALI), but the exact mechanism of pyroptosis induction and the role of Angiotensin-converting enzyme 2 (ACE2)/Ang (1-7)/Mas axis in pyroptosis has not been investigated yet. The present study aimed to establish a mice model of ALI and clarify the involvement of pyroptosis and ACE2/Ang (1-7)/Mas axis. The results showed that LPS induced pyroptosis in lung, demonstrated by increased expression of Gasdermin D (GSDMD), cleaved GSDMD, IL-1ß, and Caspase-1. Treatment of Ang (1-7) significantly reduced the severity of ALI and pyroptosis, while AngII significantly exaggerated them. Furthermore, ACE2 activator resorcinolnaphthalein (RES) significantly reduced the severity of ALI and pyroptosis, but ACE2 inhibitor MLN-4760 and Mas inhibitor A779 significantly exaggerated them, suggesting that the ACE2/Ang (1-7)/Mas axis was involved in the pyroptosis in LPS-induced ALI. In addition, Ang (1-7) and RES significantly decreased the levels of NLRP3, which were increased by AngII and A779. NLRP3 knockout significantly reduced the severity of ALI and pyroptosis. In conclusion, pyroptosis played an important role in ALI induced by LPS. The ACE2/Ang (1-7)/Mas axis negatively regulated the pyroptosis and protected mice against LPS-induced ALI through NLRP3 inhibition. The present study expanded our understating of the role of ACE2/Ang (1-7)/Mas axis in ALI by providing a novel explanation that it may regulate the pyroptosis in ALI.

Halalkalibacillus sediminis sp. nov., isolated from sediment of sea cucumber culture pond.

A Gram-stain-positive, rod-shaped (0.3-0.4×1.2-2.0 µm), strictly aerobic and beige-pigmented bacterium, designated B3227T, was isolated from the sediment of a sea cucumber culture pond in Rongcheng, China (122.2° E 36.9° N). Its biochemical characteristics analysis revealed that the cells of this bacterium were catalase-positive and oxidase-negative. Cell growth occurred at 15-45 °C (optimum, 37 °C), pH 6.5-9.0 (pH 7.5-8.0) and in the presence of 0.0-22.0 % (w/v) NaCl (6.0-9.0 % NaCl). Phylogenetic analysis based on 16S rRNA gene sequencing indicated that strain B3227T exhibited similarities of 95.7, 95.5, 95.5 and 95.3 % to the type strains of Filobacillus milensis, Piscibacillus salipiscarius, Halalkalibacillus halophilus and Piscibacillus halophilus, respectively, and the results of physiological analyses revealed that strain B3227T was most similar to the genus Halalkalibacillus. The cells were endospore-forming and comprised an A1-γ-meso-diaminopimelic acid-type peptidoglycan. The respiratory quinone of strain B3227T was MK-7, and the dominant fatty acids were anteiso-C15 : 0 and anteiso-C17 : 0. The major polar lipids were diphosphatidylglycerol and phosphatidylethanolamine. The genomic DNA G+C content was 38.7 mol%. The average nucleotide identity values between strain B3227T and H. halophilus JCM 14192T (ANIb 69.5%, ANIm 84.2 %) and F. milensis JCM 12288T (ANIb 70.1 %, ANIm 84.1 %) were below the cut-off level (95-96  %) for species delineation. The results of kegg analysis revealed that strain B3227T could biosynthesize shikimate acid, a base compound for the formulation of the swine flu drug. Based on its morphological and physiological properties, as well as phylogenetic distinctiveness, strain B3227T should be placed into the genus Halalkalibacillus as a representative of a new species, for which the name Halalkalibacillus sediminis sp. nov. is proposed. The type strain is B3227T (=KCTC 33093T=MCCC 1H00193T).

ACE2 exhibits protective effects against LPS-induced acute lung injury in mice by inhibiting the LPS-TLR4 pathway.

This study aimed to investigate the protective effect of angiotensin converting enzyme 2 (ACE2) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). After generating ALI mouse models by injecting LPS, the levels of ACE2, inflammatory factors, and downstream proteins of the LPS-TLR4 pathway were analyzed. LPS-challenged BEAS-2B cells were established in vitro. Next, a eukaryotic expression vector, pm-ACE2, was constructed and validated. Challenged cells were transfected with pm-ACE2 containing enhanced green fluorescent protein, or they were treated with D-Ala-Ang-(1-7), angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB) and the LPS-TLR4 pathway inhibitor dimethyl fumarate (DMF) for analysis of how the above factors contribute to ACE2 regulation. Expression of renin, Ang II, ACE and angiotensin II type 1 receptor (AT1R) was subsequently assessed. In the ALI model, mice exhibited decreased expression of ACE2, lung pathological injury, inflammatory injury, and abnormal activation of the LPS-TLR4 pathway. LPS-challenged BEAS-2B cells demonstrated upregulated expression of renin, Ang II, ACE and AT1R. After injection of ACE2, lung function and lung pathological injury were significantly improved, and that effect was accompanied by attenuated inflammation, and inactivation of the LPS-TLR4 pathway. Cell studies showed similar results. The above observations were further enhanced when there was a combined treatment with DMF and pm-ACE2. D-Ala-Ang-(1-7) treatment attenuated the protective effect of ACE2, while ACEI and ARB treatment alleviated LPS-induced pneumonic injury. In conclusion, ACE2 was expressed at low levels in response to LPS-induced ALI. Overexpression of ACE2 regulates the ACE2/Ang-(1-7)/Mas and ACE/Ang II/AT1 axes to maintain dynamic balance of the renin-angiotensin system, and attenuate inflammatory response.

External oxidant-free alkylation of quinoline and pyridine derivatives.

A novel and efficient method for the generation of alkyl radicals and the alkylation of quinoline and pyridine derivatives under mild conditions has been developed. This strategy allows the direct alkylation of heteroaromatics in the absence of an external oxidant. A preliminary mechanistic study suggests that the present reaction probably proceeds via an intermolecular HAT process.

Trio-based exome sequencing arrests de novo mutations in early-onset high myopia.

The etiology of the highly myopic condition has been unclear for decades. We investigated the genetic contributions to early-onset high myopia (EOHM), which is defined as having a refraction of less than or equal to -6 diopters before the age of 6, when children are less likely to be exposed to high educational pressures. Trios (two nonmyopic parents and one child) were examined to uncover pathogenic mutations using whole-exome sequencing. We identified parent-transmitted biallelic mutations or de novo mutations in as-yet-unknown or reported genes in 16 probands. Interestingly, an increased rate of de novo mutations was identified in the EOHM patients. Among the newly identified candidate genes, a BSG mutation was identified in one EOHM proband. Expanded screening of 1,040 patients found an additional four mutations in the same gene. Then, we generated Bsg mutant mice to further elucidate the functional impact of this gene and observed typical myopic phenotypes, including an elongated axial length. Using a trio-based exonic screening study in EOHM, we deciphered a prominent role for de novo mutations in EOHM patients without myopic parents. The discovery of a disease gene, BSG, provides insights into myopic development and its etiology, which expands our current understanding of high myopia and might be useful for future treatment and prevention.

A de novo pathogenic CSNK1E mutation identified by exome sequencing in family trios with epileptic encephalopathy.

Recent whole-exome sequencing (WES) studies have demonstrated the contribution of de novo mutations (DNMs) to epileptic encephalopathies (EEs). Here, we performed WES on four trios with West syndrome and identified three loss-of-function DNMs in both CSNK1E (c.885+1G>A) and STXBP1 (splicing, c.1111-2A>G; nonsense, p.(Y519X)). The splicing mutation in CSNK1E creates insertion of 116 new amino acids at position 246 followed by a premature stop codon. Both CSNK1E and STXBP1 showed a closer coexpression relationship with epilepsy candidate genes beyond that expected by chance. In addition, genes coexpressed with CSNK1E were enriched in early prenatal stages across multiple brain regions. We also found that 60 CSNK1E-interacting genes share an association with multiple neuropsychiatric disorders, and these genes formed a significant interconnected interaction network with roles in the midbrain development. Our study supported the potential role of CSNK1E variants in EE susceptibility and expanded the phenotypic spectrum associated with CSNK1E variation.

Correction: Nonrandom occurrence of multiple de novo coding variants in a proband indicates the existence of an oligogenic model in autism.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Angiotensin-converting enzyme 2 regulates autophagy in acute lung injury through AMPK/mTOR signaling.

Autophagy exerts a dual role in promoting cell death or survival. Recent studies have shown that it may play an important role in lipopolysaccharide (LPS)-induced acute lung injury (ALI). It was also suggested that angiotensin converting enzyme 2 (ACE2) may participate in the regulation of autophagy. The present study aims to investigate the role of autophagy in ALI and the involvement of ACE2. The regulation of the APMK/mTOR pathway was explored to clarify the underlying mechanism. The results showed that autophagy played an important role in ALI induced by LPS, as the autophagy inhibitor 3-methyladenine (3-MA) mitigated the severity of ALI. ACE2 activator resorcinolnaphthalein and inhibitor MLN-4760 significantly affected the histological appearance and wet/dry (W/D) ratio of the lung and altered the ACE2 activity of the lung, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels in bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) levels in lung tissue. Furthermore, LPS, resorcinolnaphthalein and MLN-4760 significantly affected the expression of autophagy proteins Beclin-1, LC3-I and LC3-II. To explore the mechanism of ACE2 on lung autophagy, we measured the phosphorylation of AMPK/mTOR after mice were treated with LPS and resorcinolnaphthalein or MLN-4760. The results revealed that resorcinolnaphthalein and MLN-4760 both significantly altered the phosphorylation of AMPK/mTOR. Finally, we found that AMPK inhibitor (8-bAMP) and mTOR activator (propranolol) both abolished the effects of ACE2 activator (resorcinolnaphthalein) on the expression of lung autophagy proteins Beclin-1, LC3-I and LC3-II. In conclusion, these findings suggest that ACE2 could alleviate the severity of ALI, inflammation and autophagy in lung tissue through the AMPK/mTOR pathway.

Pontibacter arcticus sp. nov., isolated from rhizosphere soil of Saxifraga oppositifolia.

A Gram-stain-negative, rod-shaped, red-coloured and aerobic bacterium, designated 2b14T, was isolated from rhizosphere soil of Saxifraga oppositifolia sampled at the Chinese Arctic Yellow River Station in Norway. Optimal growth occurred at 28 °C (range, 4-37 °C) and pH 7.0-7.5 (pH 6.5-8.5). The strain could tolerate up to 2.5 % (w/v) NaCl concentration. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 2b14Thad the highest similarity value of 96.0 % to Pontibacter diazotrophicus CCTCC AB 2013049T. The major fatty acids were summed feature 4 (anteiso-C17 : 1 B and/or iso-C17 : 1 I), iso-C15 : 0 and iso-C17 : 0 3-OH. The major polar lipid was found to be phosphatidylethanolamine. The genomic DNA G+C content of strain 2b14T was 45.5 mol%. The sole respiratory quinone was MK-7. The combined results of physiological, genotypic, phylogenetic and chemotaxonomic analyses showed that strain 2b14T represents a novel species within the genus Pontibacter, for which the name Pontibacter arcticus sp. nov. is proposed. The type strain is 2b14T (=KCTC 62596T=MCCC 1H00304T).

Rhodosalinus halophilus sp. nov., isolated from a marine solar saltern, and emended description of the genus Rhodosalinus.

A novel Gram-stain-negative, rod-shaped, beige-coloured, motile, facultatively anaerobic bacterium, designated as E84T, was isolated from sediment sampled from a marine solar saltern in Wendeng, PR China. Phylogenetic analysis based on 16S rRNA gene sequencing showed that Rhodosalinus sediminis WDN1C137T was the closest phylogenetic relationship, with 16S rRNA gene sequence similarity of 96.9 %. Optimal growth occurred at 33-37 °C (range, 20-40 °C), at pH 7.5 (pH 7.0-8.5) and with 6.0 % (w/v) NaCl (0.5-20.0 %). The sole respiratory quinone was Q-10. The major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C18 : 0 and cyclo C19 : 0ω8c. The polar lipids were phosphatidylglycerol, one unidentified glycolipid, two unidentified phospholipids and two unidentified lipids. The genomic DNA G+C content of strain E84T was 69.8 mol%. Based on the results of physiological, genotypic, phylogenetic and chemotaxonomic analyses, we concluded that strain E84T represents a novel species of the genus Rhodosalinus, for which the name Rhodosalinus halophilus sp. nov. is proposed. The type strain is E84T (=KCTC 52697T=MCCC 1H00231T).

Palladium-Catalyzed Hiyama Cross-Couplings of Arylsilanes with 3-Iodoazetidine: Synthesis of 3-Arylazetidines.

The first palladium-catalyzed Hiyama cross-coupling reactions of arylsilanes with 3-iodoazetidine were described. The protocol provides a convenient access to a variety of useful 3-arylazetidines which are of great interest in pharmaceutical laboratories in moderate to good yields (30%-88%). In addition, this strategy has the advantage of easy operation and mild reaction conditions.

Pedobacter changchengzhani sp. nov., isolated from soil of Antarctica.

A Gram-negative, aerobic, non-motile, pink and rod-shaped bacterium, designated E01020T, was isolated from soil collected from the Chinese Great Wall Station, Antarctica. Comparative analysis of 16S rRNA gene sequences revealed that strain E01020T is a member of the genus Pedobacter, related to Pedobacter alluvionis DSM 19624T (96.8% similarity), Pedobacter agri JCM 15120T (96.5% similarity) and Pedobacter chinensis JDX94T (96.3% similarity). The dDDH values and ANI values of strain E01020T with closely related strains indicate that it can be distinguished from them as a novel species. The DNA G+C content was determined to be 35.2 mol%. The growth of strain E01020T was observed at 4-25 °C (optimal 20 °C), in the presence of 0-1% NaCl (w/v, optimal 0%) and at pH 6.0-8.0 (optimal pH 7.0). Strain E01020T was found to contained menaquinon-7 (MK-7) as only respiratory quinone, iso-C15:0, iso-C17:0 3-OH and Summed feature 3 (C16:1ω6c and/or C16:1ω7c) as major fatty acids. The major polar lipids were phosphatidylethanolamine, one unidentified lipid and two unidentified aminolipids. On the basis of the results of the phylogenetic and phenotypic analyses, it was suggested that strain E01020T represents a novel species of the genus Pedobacter, for which the name Pedobacter changchengzhani sp. nov. is proposed. The type strain is E01020T (= KCTC 62990T = MCCC 1H00357T).

mirDNMR: a gene-centered database of background de novo mutation rates in human.

De novo germline mutations (DNMs) are the rarest genetic variants proven to cause a considerable number of sporadic genetic diseases, such as autism spectrum disorders, epileptic encephalopathy, schizophrenia, congenital heart disease, type 1 diabetes, and hearing loss. However, it is difficult to accurately assess the cause of DNMs and identify disease-causing genes from the considerable number of DNMs in probands. A common method to this problem is to identify genes that harbor significantly more DNMs than expected by chance, with accurate background DNM rate (DNMR) required. Therefore, in this study, we developed a novel database named mirDNMR for the collection of gene-centered background DNMRs obtained from different methods and population variation data. The database has the following functions: (i) browse and search the background DNMRs of each gene predicted by four different methods, including GC content (DNMR-GC), sequence context (DNMR-SC), multiple factors (DNMR-MF) and local DNA methylation level (DNMR-DM); (ii) search variant frequencies in publicly available databases, including ExAC, ESP6500, UK10K, 1000G and dbSNP and (iii) investigate the DNM burden to prioritize candidate genes based on the four background DNMRs using three statistical methods (TADA, Binomial and Poisson test). As a case study, we successfully employed our database in candidate gene prioritization for a sporadic complex disease: intellectual disability. In conclusion, mirDNMR (https://www.wzgenomics.cn/mirdnmr/) can be widely used to identify the genetic basis of sporadic genetic diseases.