Biology subjects

Sun, J.

Publications and source records attributed to Sun, J..

At least 523 records · Page 29Linked to original sources

bioRxiv2019

Universal and naked-eye gene detection platform based on CRISPR/Cas12a/13a system

Colorimetric gene detection based on gold nanoparticles (AuNPs) is an attractive detection format due to its simplicity. Here, we report a new design for a colorimetric gene-sensing platform based on the CRISPR/Cas system that has improved specificity, sensitivity, and universality. CRISPR/Cas12a and CRISPR/Cas13a have two distinct catalytic activities and are used for specific target gene recognition. Programmable recognition of DNA by Cas12a/crRNA and RNA by Cas13a/crRNA with a complementary sequence activates the nonspecific trans-ssDNA or -RNA cleavage, respectively, thus degrading the ssDNA or RNA linkers which are designed as a hybridization template for the AuNP-DNA probe pair. Target-induced trans -ssDNA or RNA cleavage leads to a distance-dependent color change for the AuNP-DNA probe pair. In this platform, naked eye detection of transgenic rice, African swine fever virus (ASFV), and a miRNA can be completed within 1 hour. Our colorimetric gene-sensing method shows superior characteristics, such as probe universality, isothermal reaction conditions, on-site detection capability, and sensitivity that is comparable to that of the fluorescent detection; thus, this method represents a robust next generation gene detection platform.

bioengineering↗

bioRxiv2019

A novel deep learning scheme for morphology-based classification of mycobacterial infection in unstained macrophages

ObjectiveMycobacterium tuberculosis (Mtb) is an airborne, contagious bacterial pathogen that causes widespread infections in humans. Using Mycobacterium marinum (Mm), a surrogate model organism for Mtb research, the present study develops a deep learning-based scheme that can classify the Mm-infected and uninfected macrophages in tissue culture solely based on morphological changes.\n\nMethodsA novel weak-and semi-supervised learning method is developed to detect and extract the cells, firstly. Then, transfer learning and fine-tuning from the CNN is built to classify the infected and uninfected cells.\n\nResultsThe performance is evaluated by accuracy (ACC), sensitivity (SENS) and specificity (SPEC) with 10-fold cross-validation. It demonstrates that the scheme can classify the infected cells accurately and efficiently at the early infection stage. At 2 hour post infection (hpi), we achieve the ACC of 0.923 {+/-} 0.005, SENS of 0.938 {+/-} 0.020, and SPEC of 0.905 {+/-} 0.019, indicating that the scheme has detected significant morphological differences between the infected and uninfected macrophages, although these differences are hardly visible to naked eyes. Interestingly, the ACC at 12 and 24 hpi are 0.749 {+/-} 0.010 and 0.824 {+/-} 0.009, respectively, suggesting that the infection-induced morphological changes are dynamic throughout the infection. Finally, deconvolution with guided propagation maps the key morphological features contributing to the classification.\n\nSignificanceThis proof-of-concept study provides a novel venue to investigate bacterial pathogenesis in a macroscopic level and has a great promise in diagnosis of bacterial infections.

bioengineering↗

bioRxiv2019

Fecal microbiota as a non-invasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver

Iron is an essential trace mineral for the growth, systemic metabolism, and immune response. Imbalance of tissue iron absorption and storage leads to various diseases. The excessive iron accumulation is associated with inflammation and cancer while iron deficiency leads to growth retardation. Studies investigated in Kenyan infants and school children suggests that both low and high iron intake result in dysbiosis of gut microbiota. This would lead to the disruption of microbial diversity, an increase of pathogen abundance and the induction of intestinal inflammation. Despite this progress, in-depth studies investigating the relationship between iron availability and gut microbiota is not completely explored. In the current study, we established a murine model to study the connection between iron and microbiota by feeding mice with either iron-deprived or -fortified diet. To identify key microbiota related to iron levels, we combined the 16S rRNA amplicon sequencing with the innovated bioinformatic algorithms, such as RDA, co-occurrence, and machine learning to identify key microbiota. Manipulation of iron levels in the diet leads to systemic iron dysregulation and dysbiosis of gut microbiota. The bioinformatic algorithms used here detect five key bacteria that correlate with systemic iron levels. Leveraging on these key microbiotas, we also established a prediction model which could precisely distinguish the individual under either iron-deprived or iron-fortified physiological condition to further prove the link between microbiota and systemic iron homeostasis. This innovated and non-invasive approach could be potentially used for the early diagnosis and therapy of iron-dysregulation related diseases, e.g. anemia, inflammatory disease, fibrosis, and cancers.

microbiology↗

bioRxiv2019

Fine-scale ecological and transcriptomic data reveal niche differentiation of an allopolyploid from diploid parents in Cardamine

Polyploidization, or whole genome duplication, is one of the major mechanisms of plant speciation. Allopolyploids (species that harbor polyploid genomes originating from hybridization of different diploid species) have been hypothesized to occupy a niche with intermediate, broader, or fluctuating environmental conditions compared with parental diploids. It remains unclear whether empirical data support this hypothesis and whether specialization of expression patterns of the homeologs (paralogous gene copies resulting from allopolyploidization) relates to habitat environments. Here, we studied the ecology and transcriptomics of a wild allopolyploid Cardamine flexuosa and its diploid parents C. hirsuta and C. amara at a fine geographical scale in their native area in Switzerland. We found that the diploid parents favored opposite extremes in terms of soil moisture, soil carbon-to-nitrogen ratios, and light availability. The habitat of the allopolyploid C. flexuosa was broader compared with those of its parental species and overlapped with those of the parents, but not at its extremes. In C. flexuosa, the genes related to water availability were overrepresented among those at both the expression level and the expression ratio of homeolog pairs, which varied among habitat environments. These findings provide empirical evidence for niche differentiation between an allopolyploid and its diploid parents at a fine scale, where both ecological and transcriptomic data indicated water availability to be the key environmental factor for niche differentiation.Significance statement Polyploidization, or whole genome duplication, is common in plants and may contribute to their ecological diversification. However, little is known about the niche differentiation of wild allopolyploids relative to their diploid parents and the gene expression patterns that may underlie such ecological divergence. We detected niche differentiation between the allopolyploid Cardamine flexuosa and its diploid parents C. amara and C. hirsuta along water availability gradient at a fine scale. The ecological differentiation was mirrored by the dynamic control of water availability-related gene expression patterns according to habitat environments. Thus, both ecological and transcriptomic data revealed niche differentiation between an allopolyploid species and its diploid parents.Competing Interest StatementThe authors have declared no competing interest.View Full Text

plant biology↗

bioRxiv2019

Inhibition of Stearoyl-CoA desaturase suppresses follicular help T and germinal center B cell responses

Stearoyl-CoA desaturases (SCD) are endoplasmic reticulum (ER) associated enzymes that catalyze the synthesis of the monounsaturated fatty acids (MUFAs). As such, SCD play important roles in maintaining the intracellular balance between saturated fatty acid (SFAs) and MUFAs. The roles of SCD in CD4+ T helper cell responses are currently unexplored. Here, we have found that murine and human follicular helper T (TFH) cells express higher levels of SCD1 compared to non-TFH cells. Further, the expression of SCD1 in TFH cells is dependent on the TFH lineage-specification transcription factor BCL6. We found that the inhibition of SCD1 impaired TFH cell maintenance and shifted the balance between TFH and follicular regulatory T (TFR) cells in the spleen. Consequently, SCD1 inhibition dampened germinal center B cell responses following influenza immunization. Mechanistically, we found that SCD inhibition led to increased ER stress and enhanced TFH cell apoptosis in vitro and in vivo. These results reveal a possible link between fatty acid metabolism and cellular and humoral responses induced by immunization or potentially, autoimmunity.

immunology↗

bioRxiv2019

High-throughput Multimodal Automated Phenotyping (MAP) with Application to PheWAS

ObjectiveElectronic health records (EHR) linked with biorepositories are a powerful platform for translational studies. A major bottleneck exists in the ability to phenotype patients accurately and efficiently. The objective of this study was to develop an automated high-throughput phenotyping method integrating International Classification of Diseases (ICD) codes and narrative data extracted using natural language processing (NLP).\n\nMethodWe developed a mapping method for automatically identifying relevant ICD and NLP concepts for a specific phenotype leveraging the UMLS. Aggregated ICD and NLP counts along with healthcare utilization were jointly analyzed by fitting an ensemble of latent mixture models. The MAP algorithm yields a predicted probability of phenotype for each patient and a threshold for classifying subjects with phenotype yes/no. The algorithm was validated using labeled data for 16 phenotypes from a biorepository and further tested in an independent cohort PheWAS for two SNPs with known associations.\n\nResultsThe MAP algorithm achieved higher or similar AUC and F-scores compared to the ICD code across all 16 phenotypes. The features assembled via the automated approach had comparable accuracy to those assembled via manual curation (AUCMAP 0.943, AUCmanual 0.941). The PheWAS results suggest that the MAP approach detected previously validated associations with higher power when compared to the standard PheWAS method based on ICD codes.\n\nConclusionThe MAP approach increased the accuracy of phenotype definition while maintaining scalability, facilitating use in studies requiring large scale phenotyping, such as PheWAS.

bioinformatics↗

bioRxiv2019

Noninvasive prenatal diagnosis for Hemophilia A by haplotype-based approach using cell-free fetal DNA in maternal plasma

ObjectivesThis study was used to demonstrate the feasibility of haplotype-based noninvasive prenatal diagnosis for Hemophilia A. MethodsTwo families affected by Hemophilia A participated in our study. Maternal haplotypes associated with pathogenic mutation was built using targeted region genotypes of mother and the proband. Combined with maternal pathogenic haplotype, a Hidden Markov Model was constructed to deduce fetal haplotype using high-coverage targeted sequencing of maternal plasma. The presence of pathogenic haplotype in male indicated affected fetus, in female indicated carrier. Prenatal diagnosis was confirmed with amniocentesis by long distance PCR. ResultsThe haplotype-based noninvasive prenatal diagnosis was successfully performed in Hemophilia A. One fetus was identified to be normal, another fetus was identified as carrier, and the results were confirmed by amniocentesis . ConclusionOur research demonstrated the feasibility of noninvasive prenatal diagnosis for Hemophilia A by haplotype-based approach.

molecular biology↗

bioRxiv2019

Amplification-free Library Preparation Improves Quality of Hi-C Analysis

PCR amplification of Hi-C libraries introduces unusable duplicates and results in a biased representation of chromatin interactions. We present a simplified, fast, and economically efficient Hi-C library preparation procedure that generates sufficient non-amplified ligation products for deep sequencing from 30 million Drosophila cells. Comprehensive analysis of the resulting data indicates that amplification-free Hi-C preserves higher complexity of chromatin interaction and lowers sequencing depth dramatically for the same number of unique paired reads. For human cells which has a large genome, this method recovers an amount of ligated fragments enough for direct high-throughput sequencing without amplification on as low as 250 thousand of cells. Comparison with published in situ Hi-C on millions of human cells reveals that amplification introduces distance-dependent amplification bias, which results in increasing background noise level against genomic distance. With amplification bias avoided, our method may produce a chromatin interaction network more faithfully reflecting the real three-dimensional genomic architecture.

genomics↗

bioRxiv2019

Haplotype-Based Noninvasive Prenatal Diagnosis for Duchenne Muscular Dystrophy: A pilot study in South China

ObjectiveTo explore the accuracy and feasibility of noninvasive prenatal diagnosis (NIPD) for Duchenne Muscular Dystrophy (DMD) based on the haplotype approach. MethodsWe recruited singleton pregnancies at-risk of DMD at 12-25 weeks of gestation from 17 families who all had a proband children affected by DMD. We have identified the pathogenic mutations in probands and their mothers by multiplex ligation-dependent probe amplification (MLPA). To construct parental haplotypes, we performed captured sequencing on genomic DNA from parents and probands. The integration analysis of parental haplotypes and targeted sequencing results of maternal plasma DNA were used to infer the fetal haplotype and genotypes in DMD gene. Fetal DMD genotypes were further confirmed by invasive prenatal diagnosis. ResultsWe have successfully performed the haplotype-based NIPD in all recruited families. Ten fetuses were identified as normal, including four female and six male fetuses. Four female fetuses were carriers and the other three male fetuses were affected by DMD with exons 49-52 deletion, exons 8-37 deletion and c.628G > T mutation, respectively. The results of NIPD were consistent with those of invasive diagnosis. ConclusionHaplotype-based NIPD for DMD by targeted sequencing is promising and has potential for clinical application.

genetics↗

bioRxiv2019

Compartmentalized Biosynthesis of Mycophenolic Acid

Mycophenolic acid (MPA) from filamentous fungi is the first natural product antibiotic in human history and a first-line immunosuppressive drug for organ transplantations and autoimmune diseases. However, its biosynthetic mechanisms have remained a long-standing mystery. Here, we elucidate the MPA biosynthetic pathway that features both compartmentalized enzymatic steps and unique cooperation between biosynthetic and {beta}-oxidation catabolism machineries based on targeted gene inactivation, feeding experiments in heterologous expression hosts, enzyme functional characterization and kinetic analysis, and microscopic observation of protein subcellular localization. Besides identification of the oxygenase MpaB as the long-sought key enzyme responsible for the oxidative cleavage of sesquiterpene side chain, we reveal the intriguing pattern of compartmentalization for the MPA biosynthetic enzymes, including the cytosolic polyketide synthase MpaC and O-methyltransferase MpaG, the Golgi apparatus-associated prenyltransferase MpaA, the endoplasmic reticulum-bound oxygenase MpaB and P450-hydrolase fusion enzyme MpaDE, and the peroxisomal acyl-CoA hydrolase MpaH. The whole pathway is elegantly co-mediated by these compartmentalized enzymes, together with the peroxisomal {beta}-oxidation machinery. Beyond characterizing the remaining outstanding steps of the MPA biosynthetic pathway, our study highlights the importance of considering subcellular contexts and the broader cellular metabolism in natural product biosynthesis.\n\nSignificance StatementHere we elucidate the full biosynthetic pathway of the fungal natural product mycophenolic acid (MPA), which represents an unsolved mystery for decades. Besides the intriguing enzymatic mechanisms, we reveal that the MPA biosynthetic enzymes are elegantly compartmentalized; and the subcellular localization of the acyl-CoA hydrolase MpaH in peroxisomes is required for the unique cooperation between biosynthetic and {beta}-oxidation catabolism machineries. This work highlights the importance of a cell biology perspective for understanding the unexplored organelle-associated essential catalytic mechanisms in natural product biosynthesis of fungi and other higher organisms. The insights provided by our work will also benefit future efforts for both industrial strain improvement and novel drug development.

biochemistry↗

bioRxiv2018

Identification of TTN as a novel candidate gene for atrioventricular block in a Chinese pedigree by whole-exome sequencing

PurposeCardiovascular diseases are the most common cause of death globally. In which atrioventricular block (AVB) is a common disorder with genetic causes, but the responsible genes have not been fully identified yet. To determine the underlying causative genes involved in cardiac AVB, here we report a three-generation Chinese family with severe autosomal dominant cardiac AVB that has been ruled out as being caused by known genes mutations.\n\nMethodsWhole-exome sequencing was performed in five affected family members across three generations, and co-segregation analysis was validated on other members of this family.\n\nResultsWhole-exome sequencing and subsequent co-segregation validation identified a novel germline heterozygous point missense mutation, c.49287C>A (p.N16429K), in the titin (TTN, NM_001267550.2) gene in all 5 affected family members, but not in the unaffected family members. The point mutation is predicted to be functionally deleterious by in-silico software tools. Our finding was further supported by the conservative analysis across species.\n\nConclusionBased on this study, TTN was identified as a potential novel candidate gene for autosomal dominant AVB; this study expands the mutational spectrum of TTN gene and is the first to implicate TTN mutations as AVB disease causing in a Chinese pedigree.

genetics↗

bioRxiv2018

Nationwide population genetic screening improves outcomes of newborn screening for hearing loss in China

PurposeConcurrent newborn hearing and genetic screening has been reported, but its benefits have not been statistically proven due to limited sample sizes and outcome data. To fill this gap, we analyzed outcomes of a large number of newborns with genetic screening results.\n\nMethodsNewborns in China were screened for 20 hearing-loss-related genetic variants from 2012-2017. Genetic results were categorized as positive, at-risk, inconclusive, or negative. Hearing screening results, risk factors, and up-to-date hearing status were followed-up via phone interviews.\n\nResultsWe completed genetic screening on one million newborns and followed up 12,778. We found that a positive genetic result significantly indicated a higher positive predictive value of the initial hearing screening (60% vs. 5.0%, P<0.001) and a lower rate of loss-to-follow-up (5% vs. 22%, P<0.001) than an inconclusive one. Importantly, 42% of subjects in the positive group with reported or presymptomatic hearing loss were \"missed\" by conventional hearing screening. Furthermore, genetic screening identified 0.23% of subjects predisposed to preventable ototoxicity.\n\nConclusionOur results demonstrate that limited genetic screening identified additional cases, reduced loss-to-follow-up, and informed families of ototoxicity risks, providing convincing evidence to support integrating genetic screening into universal newborn hearing screening programs.

genetics↗

bioRxiv2018

Global Quantitative Mapping of Enhancers in Rice Genome by STARR-seq

Identification of enhancers has been a challenge in plants. STARR-seq measures enhancer activity of millions fragments in parallel. Here we present a global map of rice enhancers quantitatively determined using STARR-seq. Most enhancers are mapped within genes, especially at the 5 untranslated regions (5 UTR) and the coding sequences. Silent and low expressed genes in genomic regions enriched with transposable elements (TEs) are frequently found containing proximal enhancers. Analysis of enhancer epigenetic features at their endogenous loci revealed that most enhancers do not co-localize with DNase I hypersensitive sites (DHSs) and are lack of H3K4me1. Clustering enhancers by their epigenetic modifications revealed that about 40% of identified enhancers carry one or more epigenetic marks. Repressive H3K27me3 is frequently enriched with positive marks of H3K4m3 and/or H3K27ac, which together may bookmark poised enhancers. Intergenic enhancers were predicted based on the location of DHS relative to genes, which overlap poorly with functionally identified enhancers. In summary, enhancers were quantitatively identified by functional analysis in a model plant genome, which provides a valuable resource for further mechanistic studies in different biological contexts.

genomics↗

bioRxiv2018

Pre-implantation genetic diagnosis for a family with Usher syndrome through targeted sequencing and haplotype analysis

ObjectiveOur objective was to investigate the applicability of targeted capture massively parallel sequencing in developing personalized pre-implantation genetic diagnosis (PGD) assay.\n\nMethodsOne couple at risk of transmitting Usher Syndrome to their offspring was recruited to this study. The genomics DNA (gDNA) was extracted from the peripheral blood and underwent in vitro fertilization (IVF)-PGD. Prenatal molecular diagnosis was performed in the 20th week of gestation and the chromosomal anomaly was analyzed.\n\nResultsCustomized capture probe targeted at USH2A gene and 350kb flanking region were designed for PGD. Eleven blastocysts were biopsied and amplified by using multiple displacement amplification (MDA) and capture sequencing. A HMM-based haplotype analysis was performed to deduce embryos genotype by using SNPs identified in each sample. Four embryos were diagnosed as free of fathers rare mutation, two were transferred and one achieved a successful pregnancy. The fetal genotype was confirmed by Sanger sequencing of fetal genomic DNA obtained by amniocentesis. The PGD and prenatal diagnosis results were further confirmed by the molecular diagnosis of the babys genomic DNA sample. The auditory test showed that the hearing was normal.\n\nConclusionTargeted capture massively parallel sequencing (MPS) is an effective and convenient strategy to develop customized PGD assay.\n\nKey pointsGenetic counseling session was conducted with a family having Usher patient who was molecularly diagnosed, and a healthy baby was born with the help of successful PGD assay. This is of vast importance in management plans since it is the first report of PGD in Usher syndrome based on targeted capture MPS.

genetics↗

bioRxiv2018

MdMYB3 helps regulate anthocyanin accumulation in apple calli under moderately acidic conditions

Anthocyanins are the key factors controlling the coloration of plant tissues. However, the molecular mechanism underlying the effects of environmental pH on the synthesis of apple anthocyanins is unclear. In this study, we analyzed the anthocyanin contents of apple calli cultured in media at different pHs (5.5, 6.0, and 6.5). The highest anthocyanin content was observed at pH 6.0. Additionally, the moderately acidic conditions up-regulated the expression of MdMYB3 as well as specific anthocyanin biosynthesis structural genes (MdDFR and MdUFGT). Moreover, the anthocyanin content was higher in calli overexpressing MdMYB3 than in the wild-type controls at different pHs. Yeast one-hybrid assay results indicated that MdMYB3 binds to the MdDFR and MdUFGT promoters in vivo. An analysis of the MdDFR and MdUFGT promoters revealed multiple MYB-binding sites. Meanwhile, electrophoretic mobility shift assays confirmed that MdMYB3 binds to the MdDFR and MdUFGT promoters in vitro. Furthermore, GUS promoter activity assays suggested that the MdDFR and MdUFGT promoter activities are enhanced by acidic conditions, and the binding of MdMYB3 may further enhance activity. These results implied that an acid-induced apple MYB transcription factor (MdMYB3) promotes anthocyanin accumulation by up-regulating the expression of MdDFR and MdUFGT under moderately acidic conditions.

molecular biology↗

bioRxiv2018

Noninvasive prenatal test of methylmalonic academia cblC type through targeted sequencing of cell-free DNA in maternal plasma

Methylmalonic acidemia (MMA) cblC type is the most frequent inborn error of intracellular cobalamin metabolism which is caused by mutations of MMACHC gene. Non-invasive test of MMA for pregnant women facilitates safe and timely prenatal diagnosis of the disease. In our study, we aimed to design and validate a haplotype-based noninvasive prenatal test (NIPT) method for cblC type of MMA. Targeted capture sequencing using customized hybridization was performed utilizing gDNA (genomic DNA) of trios including parents and an affected proband to determine parental haplotypes associated with the mutant and wild allele. The fetal haplotype was inferred later based on the high depth sequencing data of maternal plasma as well as haplotype linkage analysis. The fetal genotypes deduced by NIPT were further validated by amniocentesis. Haplotype-based NIPT was successfully performed in 21 families. The results of NIPT of 21 families were all consistent with invasive prenatal diagnosis, which was interpreted in a blinded fashion. Three fetuses were identified as compound heterozygosity of MMACHC, 9 fetuses were carriers of MMACHC variant, and 9 fetuses were normal. These results indicated that the haplotype-based NIPT for MMA through small target capture region sequencing is technically accurate and feasible.

genetics↗

bioRxiv2018

The biochemical properties of a novel paraoxonase-like enzyme in Trichoderma atroviride strain T23 involved in the degradation of 2,2-dichlorovinyl dimethyl phosphate

Dichlorvos, is a broad-spectrum organophosphorus pesticide that is widely applied in the agricultural industry and considered a pollutant to fish and bees. T. atroviride strain T23, an efficient DDVP-degrading strain, could convert DDVP to dichloroacetic acid, 2,2-dichloroethanol and phosphoric acid through mineralization. RT-qPCR analysis showed TaPon1-like encoding an organophosphorus hydrolase, is continuously highly expressed in the process of degrading DDVP. TaPon1-like contained an open reading frame of 1317 bp, and the deduced amino acid sequence shared 21% homology with HuPON1, which also exhibits excellent hydrolysis of organophosphate-oxons compounds. By analysis of gene knockout, we found the {Delta}TaPon1-like knockout strain KO1 lost 35.6% of its DDVP-degradation capacity at 24 h, but this loss of degradation activity was recovered when the gene was complemented. Furthermore, the purified recombinant protein reTAPON1-LIKE, could transform DDVP only to dimethyl phosphate and showed significant paraoxonase activity (1028 U L-1). The reTAPON1-LIKE enzyme showed a broad degradation spectrum, degrading not only DDVP but also organophosphate-oxons and lactone. The kinetic parameters (Km and kcat) of the purified reTAPON1-LIKE were determined to be 0.23 mM and 204.3 s-1 for DDVP, respectively. The highest activity was obtained at 35 {degrees}C, and the optimal pH was 8.5. The activity of reTAPON1-LIKE was enhanced most significantly when 1.0 mM Ca2+ was added but declined when 1.0 mM Cu2+ was added. These results showed TAPON1-LIKE play an important role for DDVP degradation in the first step by T23 and provided clue to comprehensively understanding the degradation mechanism of organophosphate-oxons pesticides by filamentous fungi.\n\nImportanceThe large amounts of residues of organophosphate pesticides in agroecological system has become a great threat to the safety of environment and humans. Bioremediation in association with microbial is innovative technology having a potential to alleviate such pollution problems. The genus Trichoderma is genetically diverse with capabilities to degrade chemical pesticides among different strains with agricultural significance. As a typical organophosphorus pesticide, it is one of the most employed compounds of the family. Though it was classified as a highly toxic pesticide by WHO due to its hazardous properties, it plays an important role in the control of plant pests, food storage and homes, as well as to treat infections in livestock. Therefore, we use DDVP as a model of organophosphate pesticide to study the mechanism of Trichoderma degrading organophosphate pesticides, for the aim of globally understanding molecular mechanism of enzymatic degradation of organophosphate pesticides by beneficial fungi.

microbiology↗

bioRxiv2018

Diagnostic Whole Exome Sequencing in Patients with Short Stature

Short stature is among the most common reasons for children being referred to the pediatric endocrinology clinics. The cause of short stature is broad, in which genetic factors play a substantial role, especially in primary growth disorders. However, identifying the molecular causes for short stature remains as a challenge because of the high heterogeneity of the phenotypes. Here, whole exome sequencing (WES) was used to identify the genetic causes of short stature with unknown etiology for 20 patients aged from 1 to 16 years old. The genetic causes of short stature were identified in 9 of the 20 patients, corresponding to a molecular diagnostic rate of 45%. Notably, in 2 of the 9 patients identified with genetic causes, the diagnosed diseases based on WES are different from the original clinical diagnosis. Our results highlight the clinical utility of WES in the diagnosis of rare, high heterogeneity disorders.

genetics↗