Biology subjects

Qiu, S.

Publications and source records attributed to Qiu, S..

7 recordsLinked to original sources

bioRxiv2018

Molecular profiles and mutation burden analysis in Chinese patients with gastric carcinoma

The goal of this work was to investigate the molecular profiles and mutation burden in Chinese patients with gastric carcinoma (GC). In total, we performed whole exome sequencing (WES) on 74 GC patients with tumor and adjacent normal formalin-fixed, paraffin-embedded (FFPE) tissue samples. The mutation spectrum of these samples showed a high concordance with TCGA and other studies on GC. We found the alterations of 17 DNA repair genes (including BRCA2, POLE and MSH3, etc.) were strongly correlated with the tumor mutation burden (TMB) and tumor neoantigen burden (TNB) of GC patients. Patients with mutations of these genes tend to have high TMB (median of TMB = 12.77, p=2.3e-6) and TNB (median of TNB = 5.97, p= 2.8e-3). In addition, younger GC patients (age < 60) have lower TMB (p = 0.0021) and TNB (p = 0.034) than older patients (age >= 60). Furthermore, we found a list of 18 genes and two genomic regions (1p36.21 and Xq26.3) were associated with peritoneal metastasis (PM) of GC, and patients with amplification of 1p36.21 and Xq26.3 have a worse prognosis (p=0.002, 0.01, respectively). Our analysis provides GC patients with potential markers for single and combination therapies.

cancer biology↗

bioRxiv2018

5-Hydroxymethylcytosines from Circulating Cell-free DNA as Diagnostic and Prognostic Markers for Hepatocellular Carcinoma

The lack of highly sensitive and specific diagnostic biomarkers is a major contributor to the poor outcomes of patients with hepatocellular carcinoma (HCC), the second-most common cause of cancer deaths worldwide. We sought to develop a clinically convenient and minimally-invasive approach that can be deployed at scale for the sensitive, specific, and highly reliable diagnosis of HCC, and to evaluate the potential prognostic value of this approach. The study cohort comprised of 2,728 subjects, including HCC patients (n = 1,208), controls (n = 965) (572 healthy individuals and 393 patients with benign lesions), as well as patients with chronic hepatitis B infection (CHB) (n =291), liver cirrhosis (LC) (n = 110), and cholangiocarcinoma (CCC) (n = 154), was recruited from three major liver cancer hospitals in Shanghai, China, from July 2016 to November 2017. Circulating cell-free DNA (cfDNA) were collected from plasma samples from these individuals before surgery or any radical treatment. Applying our 5hmC-Seal technique, the summarized 5-hydroxymethylcytosine (5hmC) profiles in cfDNA were obtained. Molecular annotation analysis suggested that the profiled 5hmC loci in cfDNA were enriched with liver tissue-derived regulatory markers (e.g., H3K4me1). We showed that a weighted diagnostic score (wd-score) based on 117 genes detected using the summarized 5hmC profiles in cfDNA accurately distinguished HCC patients from controls (AUC = 95.1%; 95% CI, 93.6-96.5%) in the validation set, markedly outperformed -fetoprotein (AFP) with superior sensitivity. The wd-scores, which not only detected early BCLC stages (e.g., Stage 0: AUC = 96.2%; 95% CI,94.1-98.4%) and small tumors (e.g., < 2 cm: AUC = 95.7%; 95% CI: 93.6-97.7%), also showed high capacity for distinguishing HCC from non-cancer patients with CHB/LC (AUC = 80.2%; 95% CI, 75.8-84.6%). Moreover, the prognostic value of 5hmC markers in cfDNA was evaluated for HCC recurrence, showing that a weighted prognostic score (wp-score) based on 16 marker genes predicted the recurrence risk (HR = 6.67; 95% CI, 2.81-15.82, p < 0.0001) in 555 patients who have been followed up after surgery. In conclusion, we have developed and validated a robust 5hmC-based diagnostic model that can be applied routinely with clinically feasible amount of cfDNA (e.g., from ~2-5 mL of plasma). Applying this new approach in the clinic could significantly improve the clinical outcomes of HCC patients, for example by early detection of those patients with surgically resectable tumors or as a convenient disease surveillance tool for recurrence.

cancer biology↗

bioRxiv2018

Mixed-cropping systems of different rice cultivars have grain yield and quality advantages over mono-cropping systems

Mixed-cropping system is a centuries-old cropping technique that is still widely practiced in the farmers field over the globe. Increased plant diversity enhances farmland biodiversity, which would improve grain yield and quality; however, the impacts of growing different rice cultivars simultaneously were rarely investigated. In present study, five popular rice cultivars were selected and ten mixture combinations were made according to the growth period, plant height, grain yield and quality, and pest and disease resistance. Seedlings of the five cultivars and ten mixture combinations (mixed-sowing of the seeds in an equal ratio, then mixed-transplanting and finally mixed-harvesting) were grown in plastic pots under greenhouse during the early and late growing seasons in 2016. Results showed that, compared with the corresponding mono-cropping systems, almost all combinations of the mixed-cropping systems have advantages in yield related traits and grain quality. Compared with the mono-cropping systems in the early and late growing seasons in 2016, mixed-cropping systems increased the number of spikelets per panicle, seed-setting rate, and grain weight per pot and harvest index by 19.52% and 5.77%, 8.53% and 4.41%, 8.31% and 4.61%, and 10.26% and 6.98%, respectively (paired t-test). In addition, mixed-cropping systems reduced chalky rice rate and chalkiness degree by 33.12% and 43.42% and by 30.11% and 48.13% in the early and late growing seasons, respectively (paired t-test). These results may be due to enhanced SPAD indexes and photosynthetic rates at physiology maturity in mixed-cropping systems. In general, it was found that mixed-cropping with different rice cultivars have potential for increasing grain yield and improving grain quality.

ecology↗

bioRxiv2018

Drosophila egg-derived tyrosine phosphatase (EDTP): a novel target for improved survivorship to prolonged anoxia and cellular protein aggregates

Drosophila egg-derived tyrosine phosphatase (EDTP), a lipid phosphatase that removes 3-position phosphate at the inositol ring, has dual functions in the oogenesis and the muscle performance during adult stages. A mammalian homologous gene MTMR14, which encodes the myotubularin-related protein 14, negatively regulates autophagy. Mutation of EDTP/MTMR14, however, causes at least three deleterious consequences: (1) lethality in the early embryogenesis in Drosophila; (2) \"jumpy\" phenotype with apparently impaired motor functions; and (3) association with a rare genetic disorder called centronuclear myopathy. Here we show that flies carrying a heterozygous EDTP mutation had increased survivorship to prolonged anoxia; tissue-specific downregulation of EDTP in non-muscle tissues, particularly motoneurons, extended the lifespan; and tissue-specific downregulation of EDTP in motoneurons improved the survivorship to beta-amyloid peptides (A{beta}42) and polyglutamine (polyQ) protein aggregates. MTMR14 expression was evident in the hippocampus and cortex in C57BL/6J and APP/PS1 mice. Compared with C57BL/6J mice, APP/PS1 mice had reduced MTMR14 in the cortex but not in the hippocampus. Hippocampal expression of MTMR14 was increased and plateaued at 9-17 months compared with 2-6 months in C57BL/6J mice. A{beta}42 treatment increased the expression of MTMR14 in the primarily cultured hippocampal neurons of Sprague/Dawley rats and mouse Neuro2a neuroblasts. We demonstrated a novel approach of tissue-specific manipulation of the disease-associated gene EDTP/MTMR14 for lifespan extension and the improvement of survivorship to cellular protein aggregates.

genetics↗

bioRxiv2017

Persistent one-way walking in a circular arena in Drosophila melanogaster Canton-S strain

We describe persistent one-way walking of Drosophila melanogaster in a circular arena. Wild-type Canton-S adult flies walked in one direction, counter-clockwise or clockwise, for minutes, whereas white-eyed mutant w1118 changed directions frequently. Locomotion in the circular arena could be classified into four components: counter-clockwise walking, clockwise walking, nondirectional walking and pausing. Genetic analysis revealed that while wild-type genetic background was associated with reduced directional change and reduced numbers of one-way (including counterclockwise and clockwise) and nondirectional walks, the white (w+) locus promoted persistent oneway walking by increasing the maximal duration of one-way episodes. The promoting effect of w+ was further supported by the observations that (1) w+ duplicated to the Y chromosome, (2) four genomic copies of mini-white inserted on the autosomes, and (3) pan-neuronal overexpression of the White protein increased the maximal duration of one-way episodes, and that RNAi knockdown of w+ in the neurons decreased the maximal duration of one-way episodes. These results suggested a pleiotropic function of w+ in promoting persistent one-way walking in the circular arena.

animal behavior and cognition↗

bioRxiv2017

Tissue-specific downregulation of EDTP removes polyglutamine protein aggregates and extends lifespan in Drosophila

Drosophila egg-derived tyrosine phosphatase (EDTP, also called JUMPY) is a lipid phosphatase essential in oogenesis and muscle function in the adult stage. Although mammalian JUMPY negatively regulates autophagy, loss-of-JUMPY causes muscle dysfunction and is associated with a rare genetic disorder called centronuclear myopathy. Here we show that tissue-specific downregulation of EDTP in Drosophila non-muscle tissues, particularly glial cells, suppresses the expression of polyglutamine (polyQ) protein aggregates in the same cells and improves survival. Additionally, tissue-specific downregulation of EDTP in glial cells or motoneurons extends lifespan. We demonstrate an approach to fine-tune the expression of a disease-associated gene EDTP for the removal of polyQ protein aggregate and lifespan extension in Drosophila.

genetics↗

bioRxiv2017

Behavioral decoding of Drosophila locomotionin a circular arena

The Drosophila melanogaster white-eyed w1118 line serves as a blank control, allowing genetic recombination of any gene of interest along with a readily recognizable marker. w1118 flies display behavioral susceptibility to environmental stimulation such as light. It is of great importance to characterize the behavioral performance of w1118 flies because this would provide a baseline from which the effect of the gene of interest could be differentiated. Little work has been performed to characterize the walking behavior in adult w1118 flies. Here we show that pulsed light stimulation increased the regularity of walking trajectories of w1118 flies in circular arenas. We statistically modeled the distribution of distances to center and extracted the walking structures of w1118 flies. Pulsed light stimulation redistributed the time proportions for individual walking structures. Specifically, pulsed light stimulation reduced the episodes of crossing over the central region of the arena. An addition of four genomic copies of mini-white, a common marker gene for eye color, mimicked the effect of pulsed light stimulation in reducing crossing in a circular arena. The reducing effect of mini-white was copy-number-dependent. These findings highlight the rhythmic light stimulation-evoked modifications of walking behavior in w1118 flies and an unexpected behavioral consequence of mini-white in transgenic flies carrying w1118 isogenic background.

bioinformatics↗