Biology subjects

Zhang, P.

Publications and source records attributed to Zhang, P..

25 records · Page 2Linked to original sources

bioRxiv2017

The PTPRT pseudo-phosphatase domain is a denitrase

Protein tyrosine nitration occurs under both physiological and pathological conditions1. However, enzymes that remove this protein modification have not yet been identified. Here we report that the pseudo-phosphatase domain of protein tyrosine receptor T (PTPRT) is a denitrase that removes nitro-groups from tyrosine residues in paxillin. PTPRT normally functions as a tumor suppressor and is frequently mutated in a variety of human cancers including colorectal cancer2,3. We demonstrate that some of the tumor-derived mutations located in the pseudophosphatase domain impair the denitrase activity. Moreover, PTPRT mutant mice that inactivate the denitrase activity are susceptible to carcinogen-induced colon tumor formation. This study uncovers a novel enzymatic activity that is involved in tumor suppression.

cancer biology↗

bioRxiv2017

High resolution in situ structural determination of heterogeneous specimen

Macromolecular complexes are intrinsically flexible and often challenging to purify for structure determination by single particle cryoEM. Such complexes may be studied in situ using cryo-electron tomography combined with sub-tomogram alignment and classification, which in exceptional cases reaches sub-nanometer resolution, yielding insight into structure-function relationships. All maps currently deposited in the EMDB with resolution < 9 [A] are from macromolecules that form ordered structural arrays, like viral capsids, which greatly simplifies structural determination. Extending this approach to more common specimens that exhibit conformational or compositional heterogeneity, and may be available in limited numbers, remains challenging. We developed emClarity, a GPU-accelerated image processing package, specifically to address fundamental hurdles to this aim, and demonstrate significant improvements in the resolution of maps compared to those generated using current state-of-the-art software. Furthermore, we devise a novel approach to sub-tomogram classification that reveals functional states not previously observed with the same data.\n\nThe software is freely available from https://www.github.com/bHimes/emClarity\n\nTutorial documentation and videos at https://www.github.com/bHimes/emClarity/wiki

biophysics↗

bioRxiv2017

Ennet: exert enhaner-only somatic mutations to discover potential cancer-driving biological networks

Whole genome sequencing technology has facilitated the discovery of a large number of somatic mutations in enhancers (SMEs), whereas the utility of SMEs in tumorigenesis has not been fully explored. Here we present Ennet, a method to comprehensively investigate SMEs enriched networks (SME-networks) in cancer by integrating SMEs, enhancer-gene interactions and gene-gene interactions. Using Ennet, we performed a pan-cancer analysis in 2004 samples from 8 cancer types and found many well-known cancer drivers were involved in the SME-networks, including ESR1, SMAD3, MYC, EGFR, BCL2 and PAX5. Meanwhile, Ennet also identified many new networks with less characterization but have potentially important roles in cancer, including a large SME-network in medulloblastoma (MB), which contains genes enriched in the glutamate receptor and neural development pathways. Interestingly, SME-networks are specific across cancer types, and the vast majority of the genes identified by Ennet have few mutations in gene bodies. Collectively, our work suggests that using enhancer-only somatic mutations can be an effective way to discover potential cancer-driving networks. Ennet provides a new perspective to explore new mechanisms for tumor progression from SMEs.

bioinformatics↗

bioRxiv2017

Hot-starting software containers for bioinformatics analyses

Using software containers has become standard practice to reproducibly deploy and execute biomedical workflows on the cloud. We demonstrate that hot-starting, from containers that have been frozen after the application has already begun execution, reduces the costs of cloud computing by avoiding repetitive initialization steps. The method is widely applicable and can provide substantial savings both for small jobs and for large-scale deployments using automated schedulers.

bioinformatics↗

bioRxiv2017

A Cassava Drought Inducible CC-Type Glutaredoxin, MeGRX232, Negatively Regulates Drought Tolerance In Arabidopsis By Inhibition Of ABA-Dependent Stoma

CC-type glutaredoxins (GRXs) are a land plant-specific GRX subgroup that evolved from CGFS GRXs, and participate in organ development and stress responses through the regulation of transcription factors. Here, genome-wide analysis identified 18 CC-type GRXs in the cassava genome, of which six (MeGRX058, 232, 360, 496, 785, and 892) were induced by drought and ABA stress in cassava leaves. Furthermore, we found that overexpression of MeGRX232 results in drought hypersensitivity in soil-grown plants, with a higher water loss rate, but with increased tolerance of mannitol and ABA in Arabidopsis on the sealed agar plates. The ABA induced stomatal closure is impaired in MeGRX232-OE Arabidopsis. Further analysis reveals that the overexpression of MeGRX232 leads to more ROS accumulation in guard cells. MeGRX232 can interact with TGA5 from Arabidopsis and MeTGA074 from cassava in vitro and in vivo. The results of microarray assays show that MeGRX232-OE affected the expression of a set of drought and oxidative stress related genes. Taken together, we demonstrated that CC-type GRXs involved in ABA signal transduction and play roles in response to drought through regulating stomatal closure.\n\nNovelty statementWe found that drought and ABA stress induced the transcription of CC-type glutaredoxins (GRXs) in cassava leaves. Ectopic expression of one of them, MeGRX232 in Arabidopsis affected the sensitivity to abscisic acid (ABA) and mannitol, and caused drought hypersensitivity by impairment of ABA-dependent stomatal closure.

molecular biology↗

bioRxiv2017

Cross reactivity of antibodies against microbial proteins to human tissues as basis of Crohns disease and other autoimmune diseases

BackgroundAutoimmune disease is generally a systemic inflammatory response with production of autoantibodies. In this study, we investigated the anti-microbial antibodies in circulation in cases of Crohns disease (CD), Sjogrens syndrome (SS) and other autoimmune disease and their roles in the pathogenesis of these autoimmune diseases.\n\nMaterial and methodsWestern blot was used to determine the reactivity of human plasmas from patients with CD and SS as the primary antibodies against the whole microbial extracts. The microbial proteins reactive to patients plasma were further identified and the modified sandwich ELISA assays were used to determine the blood levels of antibodies against these microbial proteins in patients with CD and SS. Antibodies against the microbial proteins are used for immunohistochemical staining of normal human tissue.\n\nResultsA group of 7 microbial proteins was identified reactive to the plasmas of patients with CD and SS including DNA-directed RNA polymerase B (RPOB), and elongation factor G (EF-G) from Staphylococcus aureus and Staphylococcus pseudintermedius (S. aureus and S. pseudintermedius), ATP synthase alpha (ATP5a) and heat shock protein 65 (Hsp65) from Mycobacterium avium subspecies paratuberculosis (MAP), elongation factor Tu (EF-Tu) and outer membrane porin C (ompC) from Escherichia Coli (E. coli). Anti-microbial antibodies can cross-react to normal human tissues. The levels of antibodies against the microbial proteins are significantly elevated in the patients with CD and SS.\n\nConclusionThe levels of antibodies against the microbial proteins are significantly elevated in CD and SS. The cross-reactivity of the anti-microbial antibodies to human tissue provides a new mechanism of pathogenesis of autoimmune diseases such as CD and SS.

microbiology↗

bioRxiv2017

Transposons modulate transcriptomic and phenotypic variation via the formation of circular RNAs in maize

Circular RNAs (circRNAs) are covalently closed, single-stranded RNA molecules. Recent studies in human showed that circRNAs can arise via transcription of reverse complementary pairs of transposons. Given the prevalence of transposons in the maize genome and dramatic genomic variation driven by transposons, we hypothesize that transposons in maize may be involved in the formation of circRNAs and further modulate phenotypic variation. To test our hypothesis, we performed circRNA-Seq on B73 seedling leaves and integrate these data with 977 publicly available mRNA-Seq datasets. We uncovered 1,551 high-confidence maize circRNAs, which show distinct genomic features as compared to linear transcripts. Comprehensive analyses demonstrated that LINE1-like elements (LLE) and their Reverse Complementary Pairs (LLERCPs) are significantly enriched in the flanking regions of circRNAs. Interestingly, the accumulation of circRNA transcripts increases, while the accumulation of linear transcripts decreases as the number of LLERCPs increases. Furthermore, genes with LLERCP-mediated circRNAs are enriched among loci that are associated with phenotypic variation. These results suggest that LLERCPs can modulate phenotypic variation by the formation of circRNAs. As a proof of concept, we showed that the presence/absence variation of LLERCPs could result in expression variation of one cicrRNA, circ352, and further related to plant height through the interaction between circRNA and functional linear transcript. Our first glimpse of circRNAs uncovers a new role for transposons in the modulation of transcriptomic and phenotypic variation via the formation of circRNAs.

genomics↗