Day 2 :
Keynote Forum
Jun Zhu
Zhejiang University, China
Keynote: Mixed linear model approaches of association mapping for complex traits based on omics variants
Time : 09:05-10:05
Biography:
Jun Zhu has completed his PhD co-major in Statistics and Genetics from NC State University and Post-doctoral studies from NC State University Department of Statistics. He is now the Director of Institute of Bioinformatics, and has been serving as Dean of College and Vice-President in Zhejiang University. He has published more than 260 papers with more than 9000 citations in reputed journals.
Abstract:
Complex traits are controlled by 4 omics variants of SNPs, transcripts, proteins, and metabolites. We proposed mixed linear model approaches for association mapping SNPs (QTSs), transcripts (QTTs), proteins (QTPs) and metabolites (QTMs) to complex traits. Precise prediction for genetic architecture of complex traits has been impeded by the limited understanding on genetic effects of complex traits, especially on locus-by-locus interaction (GxG) and locus-by-environment interaction (GxE). The analysis of large omics datasets, especially two-loci interaction analyses, involves intensive computation. A GPU-based mapping software (QTXNetwork) has been developed for detecting multiple loci on large-scale omics data, and for estimating variance components of genetic effects. By analyzing datasets of SNPs and transcripts for mouse and drosophila datasets, we demonstrated that unbiased estimation could be obtained for genetic effects of causal loci. Transcript association can efficiently detect causal transcript loci on complex traits (QTTs), and on other transcripts (tQTTs). Complicated genetic networks of transcripts controlled by other omics variables can also be revealed for SNPs (tQTSs), proteins (tQTPs) and metabolites (tQTMs). Association mapping for startle in Drosophila revealed high heritability for 85 QTTs (0.996) and 48 QTSs (0.935). The QTTs were also controlled by other 86 tQTTs (0.804~0.998) and 25 tQTSs (0.115~0.423). Both real data analyses and Monte Carlo simulations demonstrated that genetic effects and environment interaction effects could be estimated with no bias and high statistical power by using the proposed approaches.
Keynote Forum
Lyudmila Gulyaeva
Russian Novosibirsk State University, Russia
Keynote: MicroRNA expression profile in breast cancer
Time : 10:05-11:05
Biography:
Lyudmila Gulyaeva, PhD, Doctor of Biology is currently a Professor of Molecular Biology and Biochemistry at Novosibirsk State University, Head of the Molecular Carcinogenesis Laboratory of Institute of Molecular Biology and Biophysics, Novosibirsk, Russia. She got her PhD in Biochemistry in 1986 and Doctor Degree in 2000. She has spent most of her scientific carrier studying drug-metabolizing enzymes and their associations with cancer. A special interest of her research is receptor-mediated mechanism of hormone-related cancer and role of microRNA in regulation of target genes. The results of her scientific activity were published in over 180 scientific papers.
Abstract:
MicroRNAs (miRs) play an essential role in epigenetic alterations of gene expression. Dysregulation of microRNAs expression was observed in many types of cancer including breast cancer (BC). We aimed to determine the microRNA expression in breast tumor samples (n=149) with various receptor phenotypes. Bioinformatics analyses with help of the “Pathway Studio” program determined potential microRNAs: miR-21, 221, 200а, 146, 17, 27, 155, 125 and 16, which are significantly correlated with the expression of ER, PR and HER2. Our study has shown that expression of oncogenic miR-21 and miR-221 increased mainly in the triple negative BC (TNBC), whereas miR-200a and miR-146 were highly expressed in the ER-positive BC. The decreased expression of miR-17 was found in TNBC. There was no significant correlation between miR-27,-155 expression and BC phenotypes. For the first time, we have shown that the elevated level of miR-16 expression is correlated with high expression of ER and HER2. The in silico analysis has shown that studied oncogenic miRs can target ERα, PR, CYP19. Moreover, the expression profile of miR-21, 221, 155, 222 and 205 can change under neoadjuvant radio- and chemotherapy of BC patients. To understand the reasons for the changes in the miR profile, we have studied the expression of studied miRs together with miR-326,-3573,-483,-126a,--1843a,-190a,-6327, their “host” genes and target mRNAs, involved in cell proliferation and differentiation in liver, breast, ovaries and uterus of rats treated with DDT and benzo(a)pyrene. Tissue-specific expression of studied miRs was found, that could be explained by the tissue-specific activation of nuclear receptors by xenobiotics. Thus, the results confirmed the role of microRNAs in carcinogenesis of mammary gland that may open new strategies in breast cancer diagnostics and treatment.
- Track 4: Epigenetics
Track 5: Transcriptional Regulation & Attenuation
Track 6: Expression Profiling
Chair
Michael Abend
Bundeswehr Institute of Radiobology, Germany
Co-Chair
Lyudmila Gulyaeva
Russia Novosibirsk State University, Russia
Session Introduction
Lyudmila Gulyaeva
Russia Novosibirsk State University, Russia
Title: MicroRNA Expression Profile in Breast Cancer
Time : 11:20: 1 1:50
Biography:
Lyudmila Gulyaeva, PhD, Doctor of Biology is currently a Professor of Molecular Biology and Biochemistry at Novosibirsk State University, Head of the Molecular Carcinogenesis Laboratory of Institute of Molecular Biology and Biophysics, Novosibirsk, Russia. She got her PhD in Biochemistry in 1986 and Doctor Degree in 2000. She has spent most of her scientific carrier studying drug-metabolizing enzymes and their associations with cancer. A special interest of her research is receptor-mediated mechanism of hormone-related cancer and role of microRNA in regulation of target genes. The results of her scientific activity were published in over 180 scientific papers.
Abstract:
MicroRNAs (miRs) play an essential role in epigenetic alterations of gene expression. Dysregulation of microRNAs expression was observed in many types of cancer including breast cancer (BC). We aimed to determine the microRNA expression in breast tumor samples (n=149) with various receptor phenotypes. Bioinformatics analyses with help of the “Pathway Studio” program determined potential microRNAs: miR-21, 221, 200а, 146, 17, 27, 155, 125 and 16, which are significantly correlated with the expression of ER, PR and HER2. Our study has shown that expression of oncogenic miR-21 and miR-221 increased mainly in the triple negative BC (TNBC), whereas miR-200a and miR-146 were highly expressed in the ER-positive BC. The decreased expression of miR-17 was found in TNBC. There was no significant correlation between miR-27,-155 expression and BC phenotypes. For the first time, we have shown that the elevated level of miR-16 expression is correlated with high expression of ER and HER2. The in silico analysis has shown that studied oncogenic miRs can target ERα, PR, CYP19. Moreover, the expression profile of miR-21, 221, 155, 222 and 205 can change under neoadjuvant radio- and chemotherapy of BC patients. To understand the reasons for the changes in the miR profile, we have studied the expression of studied miRs together with miR-326,-3573,-483,-126a,--1843a,-190a,-6327, their “host” genes and target mRNAs, involved in cell proliferation and differentiation in liver, breast, ovaries and uterus of rats treated with DDT and benzo(a)pyrene. Tissue-specific expression of studied miRs was found, that could be explained by the tissue-specific activation of nuclear receptors by xenobiotics. Thus, the results confirmed the role of microRNAs in carcinogenesis of mammary gland that may open new strategies in breast cancer diagnostics and treatment.
Julie Secombe
Einstein College of Medicine, USA
Title: KDM5: More than just a histone demethylase
Time : 11:25: 11:55
Biography:
Julie Secombe received her PhD from the University of Adelaide, Australia, studying the regulation of the cell cycle. Her Pos-tdoctoral training with Dr. Robert Eisenman at the Fred Hutchinson Cancer Center centered on defining the means by which the oncoprotein Myc regulates cell growth. She started her own research group in 2009 at the Albert Einstein College of Medicine. Her research focuses on defining mechanisms of transcriptional regulation, with particular emphasis on two transcriptional regulators, Myc and KDM5/Lid.
Abstract:
Our work focuses on understanding the functions of the transcriptional regulator KDM5. Mammalian cells encode four KDM5 paralogs, KDM5A-D, three of which are clinically important: overexpression of human KDM5A or KDM5B are associated with cancer, and mutations in KDM5A, KDM5B or KDM5C are found in patients with intellectual disability. Yet the basic mechanisms by which this family of proteins functions in a physiological setting remain largely unknown. Taking advantage of the fact that Drosophila encodes a single, essential, KDM5 paralog, we have recently found that KDM5 regulates genes essential to mitochondrial function. This finding is significant because mitochondrial dysfunction is implicated in a large number of human diseases, including cancer and cognitive dysfunction. Importantly, KDM5 regulates mitochondrial function genes independently of its well-described JmjC domain-encoded histone demethylase activity. Instead, KDM5 requires its PHD motif that binds to histone H3 that is di- or trimethylated on lysine 4 (H3K4me2/3). Genome-wide, KDM5 binding overlapped with the active chromatin mark H3K4me3, and a fly strain specifically lacking H3K4me2/3 binding showed defective KDM5 promoter recruitment and gene activation. KDM5 therefore plays a central role in regulating mitochondrial function by utilizing its ability to recognize specific chromatin contexts.
Jianbo Wang
Wuhan University, China
Title: The transcriptomic studies on rice (Oryza sativa) developing embryo and endosperm
Time : 11: 55: 12:25
Biography:
Jianbo Wang has completed his PhD from Wuhan University, China. He is interested in the research on plant reproductive development, and has published more than 40 papers in reputed journals
Abstract:
RNA-seq analysis of rice (Oryza sativa L.ssp. indica cv. 9311) developing embryo (3, 7 and 14 DAP (Days after Pollination)) generated 27,190 genes. Among these genes, the number of genes expressed stage-specifically were 1,131, 1,443 and 1,223 and a total of 1,011 differentially expressed genes were identified, while 672 genes with significant changes in expression between 3 and 7 DAP, 504 DEGs between 7 and 14 DAP. A large number of genes related to metabolism, transcriptional regulation, nucleic acid replication/processing and signal transduction were expressed predominantly in the early and middle stages of embryogenesis. In addition, we found that many transcription factor families may play important roles at different developmental stages, not only in embryo initiation but also in other developmental processes. The endosperm development has an important role for rice yield and quality. We used RNA-seq to reveal the molecular mechanisms involved in rice endosperm development. Three cDNA libraries were taken from rice endosperm at 3, 6 and 10 days after pollination (DAP), which resulted in the detection of 21,596, 20,910 and 19,459 expressed genes, respectively, and 10,371 genes were differentially expressed. A large number of genes related to ribosomes, the spliceosome and oxidative phosphorylation were found to be expressed in the early and middle stages. Plant hormone, galactose metabolism and carbon fixation related genes showed a significant increase in expression at the middle stage, whereas genes for defense against disease or response to stress as well as genes for starch/sucrose metabolism were strongly expressed during the later stages of endosperm development. The RNA-Seq result confirmed the expression characteristics of rice endosperm development.
Lyudmila Gulyaeva
Russia Novosibirsk State University, Russia
Title: Workshop on “Regulation of gene expression by xenobiotics and microRNAâ€
Time : 12:25-13:25
Biography:
Lyudmila Gulyaeva, PhD, Doctor of Biology is currently a Professor of Molecular Biology and Biochemistry at Novosibirsk State University, Head of the Molecular Carcinogenesis Laboratory of Institute of Molecular Biology and Biophysics, Novosibirsk, Russia. She got her PhD in Biochemistry in 1986 and Doctor Degree in 2000. She has spent most of her scientific carrier studying drug-metabolizing enzymes and their associations with cancer. A special interest of her research is receptor-mediated mechanism of hormone-related cancer and role of microRNA in regulation of target genes. The results of her scientific activity were published in over 180 scientific papers.
Abstract:
Gene expression is regulated by various mechanisms at transcriptional and post-transcriptional levels. Transcriptional mechanisms involve activation of transcription factors upon ligand binding or activation of signal transduction pathways. Many foreign compounds can bind specific nuclear receptors (AhR, CAR, PXR, PPARs) leading to activation of expression of target genes. Toxicity of chemicals is dependent on specific signaling pathway that involves chemical activates. Such factors as structure of chemicals, gender and species of studied animals determine the degree and kind of toxic effects of the compound. We have investigated species-specific effect of phenobarbital and different chemical modification of 2,4,6-tryphenyldioxane-1,3 (TPD) on the cytochrome P450 (CYP) – key enzyme in xenobiotic metabolism. Selective effects of closely resembling compounds on CYP2B induction on transcriptional level have been uncovered with the help of Enzyme activity assays, Western-blot, gel shift analysis and RT-qPCR. Additionally, microRNAs play important role in post-transcriptional regulation of numerous genes, in particular of the cytochrome P450. The effects caused by xenobiotics can be attributed to changes in the miRNA expression profile, thus leading to changes in gene regulation. This can explain the detrimental effects that these chemicals have on human health. We used in silico methods and experimental approaches in order to investigate whether some xenobiotics like DDT and benzo(a)pyrene affect the expression of miRNAs through the activation of nuclear receptors (NRs): CAR (DDT) and AhR (BP), as well as estrogen receptor ER1 and ER2. The study showed that expression of microRNAs might vary under xenobiotic induction through NRs activation. This effect depends on the tissue type of experimental animals. The correlation between expression of microRNAs, host genes and target genes was shown. Thus, xenobiotics can dramatically change both protein coding genes and microRNA expression profile, greatly contributing to their toxic effects including carcinogenesis.
Yongyan Sun
Chinese Academy of Sciences, China
Title: Application of Transcriptomics on study of biological effects of magnetic field exposure
Time : 14:25:15:05
Biography:
Yongyan Sun is now a PhD candidate in Institute of Urban Environment, Chinese Academy of Sciences.
Abstract:
Transcriptomics is one of functional genomic approaches widely applied in life science research in recent years. Based on the background of crosses and integration between environmental science and life science subjects, growing cutting-edged molecular technologies such as proteomics, metabolomics and etc., are applied in studying environmental problems, especially exploring biological relationships between human living environments and health. Electromagnetic environment is one of extensively existed urban environmental factors in modern life during the development of urbanization and modernization. Thus, it is indispensable and inevitable to investigate the biological effects of electromagnetic field (EMF) on human health and disease. Transcriptomic analysis, which could to some extent reflect the gene expression alteration under EMF exposure, is rewarding to much deeper understanding on molecular mechanism of living organism sensing and responsing to EMF exposure. In our study, we have explored the bio-effects of extremely low-frequency electromagnetic field (ELF-EMF) and radio frequency electromagnetic field (RF-EMF) via transcriptomic analysis on model organism, such as Saccharomyces cerevisiae, Drosophila melanogaster and Caenorhabditis elegans. Several results indicate that the living organism indeed response to EMF exposure and different model organism showed changes in various ways. Therefore, the utilization of transcriptomic approach on studying the health effect of EMF exposure lays the molecular basis for further research on mechanism of electromagnetic field sensing and responsing.
Erin E Sparks
Duke University, USA
Title: Exploring underground networks: the transcriptional control of plant root development
Time : 15:05:15:35
Biography:
Erin E Sparks received her PhD in 2011 from Vanderbilt University and is currently a Post-doctoral Associate with Philip Benfey at Duke University. She has a longstanding interest in the molecular development of branched organs.
Abstract:
Tissue-specific gene expression is often thought to arise from spatially restricted transcriptional cascades. However it is unclear how expression is established at the top of these cascades. The SHORTROOT-SCARECROW transcriptional cascade is central to cell fate decisions in the Arabidopsis root cortex and endodermis (ground tissue). We experimentally derived a gene regulatory network for transcription factors in the Arabidopsis root ground tissue by enhanced yeast-1-hybrid assays. We then used this ground tissue gene regulatory network to dissect the regulation of the SHORTROOT-SCARECROW transcriptional cascade. We validated network predictions in planta and identified regulators of SCARECROW and SHORTROOT expression. Our results suggest that there is intercellular coordination of SHORTROOT and SCARECROW expression. Further, we leveraged cell type specific transcriptome data within a logistic regression to develop a model in which expression at the top of this transcriptional cascade is established through the opposing gradients of activators and repressors.
Bao Liu
3rd Military Medical University, China
Title: Inflammatory response in the pathogenesis of acute mountain sickness revealed by transcriptome analysis
Time : 15:35:16:05
Biography:
Bao Liu is an undergraduate student at 3rd Medical University, Chongqing, China. He is studying the molecular mechanisms of high altitude illness using transcriptome.
Abstract:
Acute mountain sickness (AMS) is a common disabling condition in individuals experiencing high altitudes, which may progress to life-threatening high altitude cerebral edema. To gain further insight into the molecular underpinnings that participated in the pathophysiology of AMS. We studied paired whole blood transcriptomes from 10 individuals, 5 AMS and 5 non-AMS diagnosed by Lake Louise scoring system, comparing post-exposure to high altitude (5300 m) transcriptomes to their pre-exposure counterparts. We identified 1,164 and 1,322 differentially expressed transcripts in participants with AMS and non-AMS, respectively. Among these genes, only 328 transcripts were common in both AMS and non-AMS individuals. Moreover, immune and inflammatory responses were more enriched in participants with AMS, but not in non-AMS individuals. This study identifies that inflammatory response induced by hypoxia, may be critical in AMS pathogenesis, which is a new direction for AMS pathogenesis investigation and useful for developing pharmacological prophylaxis and treatment.