Day 2 :
- Workshop on NIH Funding Opportunities
Location: Conference Hall 1
- Big Data in Cancer Genomics | Cancer Biopsy | Whole Genome Sequencing
Location: Conference Hall 1
Tamara Lah Turnsek
National Institute of Biology, Slovenia
Mayo Clinic, USA
Institute of Genetics and Molecular and Cellular Biology, France
Time : 11:20-11:50
Nithyha Parameswaran Kalaivani has completed her Master of Science from King’s College London, UK and is currently a Doctoral student in IGBMC, France.
Post-translational modifications (PTMs) of histones have emerged as key players in the regulation of gene expression. However, little is known to what extent PTMs can directly impact chromatin. It has been suggested that PTMs of core histones (H2A, H2B, H3 and H4) have the potential to govern chromatin function according to the so called “histone code” hypothesis by recruiting specific binding proteins. The goal of my project is to gain insight in the function acetylation within the globular domain of H3 (H3K56/64/115/122) and to compare these modifications with histone tail modifications, in vivo by using the mouse ES cells. To study the impact of PTMs in vivo, all endogenous wild type (WT) H3 gene copies have to be replaced with mutant copies. Hence, the primary focus of my project is to establish a model system that exclusively express mutated H3 (e.g., mimicking acetylation) in order to study effects of H3 globular domain modifications on gene expression, chromatin architecture as well as to study, cross talks and synergisms between globular domain modifications and compare the effects with tail modifications.
University of Tampere, Finland
Title: Estimation of missing values for gene interaction data coming from high throughput technologies
Time : 11:50-12:20
Gashaw Mekuria is currently a PhD candidate in Biostatistics at University of Tampere School of Health Sciences, Finland. He holds an MSc in Bioinformatics from University of Turku, Finland and a BSc in Statistics from Addis Ababa University, Ethiopia.
Advancements in high-throughput genetic screening technologies have enabled us to systematically study how gene interactions between pairs of genes can affect phenotypes of certain traits. However, these advancements also pose other challenges to researchers in the management and analysis of the vast amount of data being produced. One of the problems related with this is the significant amount of missing interaction scores that cannot be scanned by the screening technologies or were filtered out from the datasets for technical reasons. This will significantly affect and bias downstream analysis. Therefore, there is an immediate need to impute those missing data more precisely. This study evaluates existing missing value imputation techniques on large-scale quantitative data matrices from synthetic genetic array (SGA) and epistatic mini array profiling (E-MAP) screening technologies. Different existing methods that are usually applied for imputation purposes were evaluated against various conditions and performance accuracies. This best performing imputation approach, based on weighted correlation between nearest-neighbors’, is now modified and can be used in any gene interaction data. Hereby, this study removed the limitation of a method already developed for this purpose and gives a more flexible, optimized and best performing method. This method can now be effectively used in the pre-processing of gene interaction scores by researchers towards a genome-wide analysis such as identification of global functional networks, gene clustering, etc. for a more accurate and less biased results and biological interpretations.
Pfizer Inc., USA
Title: Systems biology and functional genomics for precision medicine: A data-driven and integrative approach
Time : 12:20-12:50
Jiyang Yu received his Bachelor's degree in Computer Science from Zhejiang University, China in 2006. In 2008-2012, he did his PhD in Biomedical Informatics with Dr. Andrea Califano at Columbia University. After his PhD, he joined Pfizer Oncology as a Senior Scientist in Department of Precision Medicine. His PhD work has successfully launched two clinical trials and one biomarker patent in breast cancer. He has numerous publications in top journals including Cancer Cell, Genes & Dev, Leukemia, Cancer Research, Oncotarget and Bioinformatics, among others.
Data-driven precision or genomic medicine is coming of age. It’s increasingly easy to collect relevant “big data” from genomics to clinics. However, the interpretation of “big data” and translation into down-stream testable experimental hypotheses and patient-beneficial clinical applications or therapeutics remain difficult. In this talk, I will demonstrate how to leverage and integrate computational & systems biology analysis of cancer genomics data and genome-wide functional genomics screens by RNAi or CRISPR to identify novel driver-type therapeutic targets as well as predictive biomarkers to overcome drug-resistance and to treat aggressive human cancers. Specifically I will introduce a network-based systems biology framework to computationally infer disease drivers from large volumes of cancer genomics data and sophisticated statistical algorithms to deconvolute and analyze noisy high-throughput microarray or NGS-based functional genomics screening data. I will talk three application stories in details, two of which have successfully launched two clinical trials and one biomarker patent for specific subtypes of breast cancer.
Iran University of Medical Sciences, Iran
Title: The importance of re-examination with deep biopsies in diagnosing cervical malignancies despite multiple negative pathology reports: A case report
Time : 12:50-13:20
Azadeh Memarian has completed his Expertise in forensics from Iran University of Medical Sciences, Tehran, Iran. She is Assistant Professor of Forensic Medicine. She has published more than 25 papers in journals and has been serving as an Editorial Board Member of Tehran University Medical Journal.
Clinical symptoms of female genital tract lymphoma are often non-specific and mimic other more common gynecological malignancies. Diagnosis can only be confirmed by histology. A 48-year-old multiparous woman was referred to the gynecology clinic because of enlarged myomatous uterus and persistent heavy vaginal bleeding. She underwent a subtotal hysterectomy and unilateral salpingo-oophorectomy in a Hospital in Yazd (Iran). Intraoperatively severe bleeding occurred and dense cervical adhesions to peripheral tissues were found. Pathology report indicated benign leiomyoma. After a few months, an abdomino-pelvic CT scan was performed because of flank pain that revealed bilateral hydronephrosis. The patient was referred to the Gynecology Oncology clinic of Bahman hospital in Tehran. Pelvic and rectovaginal exam and colposcopy were performed. Biopsy report was negative, after which mycobacterium tuberculosis test showed negative results. Under general anesthesia, multiple deep cervical biopsies revealed no malignancy again. The slides were reviewed by another “referral” pathologist who reported a typical lymphoid infiltration, consistent with malignant lympho-proliferative disorder in parametrial biopsies. Immunohistochemistry confirmed the diagnosis. The stony appearance of the cervix and a concomitant frozen pelvis strongly supported the diagnosis of cervical malignancy. The role of gynecological examination in the diagnosis of genital cancer is essential. When frozen pelvis and a fixed stony cervix are present, it is necessary to perform multiple deep biopsies in spite of previous negative pathologies. Review of the slides by qualified pathologists can help achieve an accurate diagnosis. Despite histopathological errors, lymphoma should always be considered by pathologists, particularly in these unusual cases.
Shandong University, China
Time : 14:05-14:35
Xiaobo Guo has completed his PhD from Ruijin Hospital Affiliated to Shanghai Jiao Tong University and Post-doctoral studies from Provincial Hospital Affiliated to Shandong University. He is an Associate Professor in the department of gastrointestinal surgery, Shandong Provincial Hospital affiliated to university. He has published more than 15 papers in reputed journals and has been serving as an Editorial Board Member of repute.
The contribution of long non-coding RNAs (lncRNAs) to metastasis of gastric cancer remains largely unknown. In this study lncRNAs that were differentially expressed between normal gastric tissues and gastric cancer tissues were identified by microarray and validated using quantitative real-time polymerase chain reaction (qRT-PCR). Our data showed that the expression level of olfactory receptor, family 3, subfamily A, member 4 (OR3A4) was significantly associated with lymphatic metastasis, depth of cancer invasion and distal metastasis in 130 paired gastric cancer tissues. The effects of OR3A4 were assessed by over-expressing and silencing the lncRNA in gastric cancer cells. We found that OR3A4 promoted cancer cell growth, angiogenesis, metastasis, and tumorigenesis in vitro and in vivo. Using global microarray analysis combined with RTPCR, RNA immunoprecipitation and RNA pull-down analysis after OR3A4 transfection, we showed that OR3A4 influenced biologic function in gastric cancer cells by regulating the activation of PDLIM2, MACC1, NTN4 and GNB2L1. Together, our results indicate that OR3A4 is an oncogenic lncRNA that promotes tumor progression and led us to propose that lncRNAs might function as key regulatory hubs in gastric cancer progression.
Badji-Mokhtar University, Algeria
Title: CDA-NABC-cytidine deaminase activity a predictive marker of toxicity/efficacy in nucleosidic analogs-based chemotherapy
Time : 14:35-15:05
Adel Gouri has completed his PharmD from Badji Mokhtar University and Postdoctoral studies in Clinical Biochemistry from Badji Mokhtar University School of Medicine. He is a Lecturer and Research Scientist in Ibn Rochd-Annaba Hospital University. He has published more than 25 papers in reputed journals and has been serving as Editor In Chief and Editorial Board Member of repute.
Nucleoside analogues such as gemcitabine and cytarabine are widely prescribed in pediatric and adult oncology. However, large variability in clinical outcome and efficacy has been observed. Therefore, new biomarkers with predictive power to assess inter-individuals differences in clinical outcome are urgently warranted. Cytidine Deaminase (CDA) is a liver enzyme that plays a crucial role in the metabolism of nucleoside analogues, coded by a gene displaying several genetic and epigenetic polymorphisms. Consequently, CDA activity is present various phenotypes, ranging from deficient (Poor Metabolizer patients, PM), to ultra-rapid deaminator patients (Ultra-Metabolizer patients, UM), with subsequent impact on drug pharmacokinetics and pharmacodynamics eventually. Several studies showed that CDA status was well correlated with clinical outcomes in patients undergoing nucleosidic analogs-based chemotherapy. Therefore, a low CDA activity is associated with more toxicity but a higher efficacy, while a high activity will lead to a lower efficacy but less toxicity. CDA phenotypic screening and prior stratification of patients’ status should be considered as relevant strategy to personalize dosing and to improve efficacy/toxicity ratio.
Alexandria Faculty of Medicine, Egypt
Time : 15:05-15:35
Hend Abdel Gawad Shakshouk is currently an Intern at the Faculty of Medicine, Alexandria University, Egypt. She has earned her MBBCh degree and realized her passion for stem cells and regenerative medicine. She wrote her first article review about stem cells and breast cancer which has been accepted for publication. She has joined the Stem Cell Research Team at the Faculty of Medicine, Alexandria University, Egypt.
Background: Mesenchymal stem cells (MSCs) are recruited to the stroma of cancers. They interact with cancer cells to promote invasion and metastasis or to suppress tumor growth. The unique tumor-homing capacity of MSCs makes them a promising vehicle to deliver various anticancer agents.
Methods: PubMed, PubMed central, Springer and Cochrane databases were searched using specified terms.
Results: Literature search yielded 17 manuscripts; seven of which suggested the use of MSCs in breast cancer therapy, while six studies raised the possibility that MSCs may promote tumor growth and four other studies assumed a dual role for MSCs.
Conclusions: The role of MSCs in breast cancer therapy is still debatable. We recommend future research in the field of MSCs in Alexandria University as it is our hope in the fight against breast cancer.
IUniversity of Queensland, Australia
Title: Comprehensive analysis of the DNA methylation landscape in esophageal adenocarcioma and Barrett’s esophagus
Time : 15:35-16:05
Lutz Krause undertook his undergraduate studies in Computer Science and completed his PhD in Bioinformatics and Genome Research. In 2008 he has joined the Nestle in Lausanne, Switzerland, where he studied the role of the gut microbiota in health and disease. In 2010 he moved to Australia to the QIMR Berghofer Institute and in 2014 he joined the University of Queensland Diamantina Institute, to pursue his research on biomarker discovery and genetics of complex diseases. In collaboration with the Princess Alexandra Hospital, his research aims at the identification of biomarkers that help clinicians choosing the optimal treatment for individual EAC patients.
This study describes the esophageal cancer methylation landscape and its impact on gene expression. Genes aberrantly methylated suggest a mechanism that could lead to genomic instability and chromothripsis. A CIMP-like subtype with potentially worse clinical outcome was also identified. The incidence of esophageal adenocarcinoma (EAC) has risen more than 600% in the last 30 years. EAC has a poor outcome with only 13-20% of patients surviving five years. Barrett’s esophagus (BE) is a precancerous precursor of EAC. This is the first study to explore methylome, transcriptome and encode data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 125 EAC, 19 Barrett’s esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hyper-methylated sites in EAC and BE were mainly located in CpG-rich promoters. Genes aberrantly methylated showed enrichment for pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling. Also genes involved in chromosomal segregation and spindle formation were aberrantly methylated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hyper-methylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hyper-methylated tumors showed worse patient survival.
Aljouf University, KSA
Title: Metabolomic profiling, antioxidant capacity and in vitro anticancer activity of some Compositae plants growing in Saudi Arabia
Time : 16:25-16:55
Mousa O Germoush has completed his PhD from Saudi Arabia in 2009 from King Saud University after 22 years experimental period as a Biology teacher. He is an Associate Professor in Biology Department in Aljouf University, KSA. He is very much interested in researching about anticancer drugs and liver functions. He is also a Member in associations, like ACCR, US, EACR, UK and INCTR, Belgium.
The present study was conducted to evaluate the metabolic profiling, antioxidant capacity and anticancer activities of some common widely grown plants of the family Compositae. The total phenolics, flavonoids, anthocyanins, saponins, total antioxidant capacity (TAC) and 2,2-diphenyl1picrylhydrazyl (DPPH) assays were determined in the selected plant extracts. In vitro anticancer activity was also assessed using human hepatocellular carcinoma (HepG-2) and breast adenocarcinoma (MCF-7) cell lines. The plant species revealed different metabolomic profiling. Artemisia showed the highest contents of the detected secondary metabolites compared to other plant extracts. Pulcaria crispa showed the highest inhibition concentration 50% (IC50) among the screened extracts against HepG-2 (8.9 μg/ml) and MCF-7 (8.14 μg/ml). The high performance liquid chromatography analysis (HPLC) of P. crispa extract revealed the presence of high content of three phenolic compounds, benzoic, chlorogenic acid and vanillic acid, along with two polyphenolic compounds, hesperidin and quercetrin. In summary, among the screened extracts, P. crispa has the most potent anti-tumor activity in vitro against HepG-2 and MCF-7 cell lines.
Huazhong University of Science and Technology, China
Title: Global analysis of DNA methylation in hepatocellular carcinoma by a liquid hybridization capturebased bisulfite sequencing approach
Time : 16:55-17:25
Qian Chen has completed her PhD from Queen’s University of Belfast, Northern Ireland and Postdoctoral studies from National Institute of Health, USA. She serves as a Physician & Clinical Assistant Professor of Medicine, Gastrointestinal Department and Endoscopy Unit at Affiliated Tongji Hospital of Huazhong University of Science and Technology (HUST), China. She has published more than 11 papers in reputed journals and has been serving as an editorial board member of repute.
Epigenetic alterations such as aberrant DNA methylation of promoter and enhancer regions, which lead to atypical gene expression has been associated with carcinogenesis. In hepatocellular carcinoma (HCC), genome-wide analysis of methylation has only recently been used. For a better understanding of hepatocarcinogenesis, we applied an even higher resolution of the promoter methylome analysis to identify previously unknown regions and genes differentially methylated in HCC. Optimized liquid hybridization capture-based bisulfite sequencing (LHC-BS) was developed to quantitatively analyze 1.86 million CpG sites of individual sample from 8 pairs of HCC and adjacent tissues. By linking the differentially methylated regions (DMRs) in promoters to the differentially expressed genes (DEGs), we identified 12 DMR associated genes. We further utilized Illumina MiSeq combining bisulfite sequencing PCR approach to validate the 12 candidate genes. Seven genes, including SMAD6, IFITM1, LRRC4, CHST4 and TBX15 with promoter hyper-methylation and CCL20 and NQO1 with promoter hypo-methylation in HCC were confirmed in additional 78 HCC pairs by Illumina MiSeq platform. These data highlight the novel methylome profiling provides a cost-efficient approach to determine candidate genes in human HCC that may contribute to hepatocarcinogenesis. Our work provides further information critical for understanding the epigenetic processes underlying tumorigenesis and prognosis of HCC.