Biochemistry, Biophysics, and Structural Biology Commons^™

The ​Oestrogen Receptor Alpha-Regulated Lncrna ​Neat1 Is A Critical Modulator Of Prostate Cancer, Dimple Chakravarty, Andrea Sboner, Sujit S. Nair, Eugenia Giannopoulou, Ruohan Li, +16 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. Some prostate cancers escape androgen dependence and are often associated with an aggressive phenotype. The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains elusive. Using a combination of chromatin immunoprecipitation (ChIP) and RNA-sequencing data, we identified an ERα-specific non-coding transcriptome signature. Among putatively ERα-regulated intergenic long non-coding RNAs (lncRNAs), we identified nuclear enriched abundant transcript 1 (NEAT1) as the most significantly overexpressed lncRNA in prostate cancer. Analysis of two large clinical …

Hive-Hexagon: High-Performance, Parallelized Sequence Alignment For Next-Generation Sequencing Data Analysis, Luis Santana-Quintero, Hayley Dingerdissen, Jean Thierry-Mieg, Raja Mazumder, Vahan Simonyan

Biochemistry and Molecular Medicine Faculty Publications

Due to the size of Next-Generation Sequencing data, the computational challenge of sequence alignment has been vast. Inexact alignments can take up to 90% of total CPU time in bioinformatics pipelines. High-performance Integrated Virtual Environment (HIVE), a cloud-based environment optimized for storage and analysis of extra-large data, presents an algorithmic solution: the HIVE-hexagon DNA sequence aligner. HIVE-hexagon implements novel approaches to exploit both characteristics of sequence space and CPU, RAM and Input/Output (I/O) architecture to quickly compute accurate alignments. Key components of HIVE-hexagon include non-redundification and sorting of sequences; floating diagonals of linearized dynamic programming matrices; and consideration of cross-similarity …

A Framework For Application Of Metabolic Modeling In Yeast To Predict The Effects Of Nssnv In Human Orthologs, Hayley Dingerdissen, Daniel S. Weaver, Peter D. Karp, Yang Pan, Vahan Simonyan, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

Background

We have previously suggested a method for proteome wide analysis of variation at functional residues wherein we identified the set of all human genes with nonsynonymous single nucleotide variation (nsSNV) in the active site residue of the corresponding proteins. 34 of these proteins were shown to have a 1:1:1 enzyme:pathway:reaction relationship, making these proteins ideal candidates for laboratory validation through creation and observation of specific yeast active site knock-outs and downstream targeted metabolomics experiments. Here we present the next step in the workflow toward using yeast metabolic modeling to predict human metabolic behavior resulting from nsSNV.

Results

For the …

The Effect Of Tuning Cold Plasma Composition On Glioblastoma Cell Viability, Xiaoqian Cheng, Jonathan H. Sherman, William Murphy, Edward Ratovitski, Jerome Canady, Michael Keidar

Biochemistry and Molecular Medicine Faculty Publications

Previous research in cold atmospheric plasma (CAP) and cancer cell interaction has repeatedly proven that the cold plasma induced cell death. It is postulated that the reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a major role in the CAP cancer therapy. In this paper, we seek to determine a mechanism of CAP therapy on glioblastoma cells (U87) through an understanding of the composition of the plasma, including treatment time, voltage, flow-rate and plasma-gas composition. In order to determine the threshold of plasma treatment on U87, normal human astrocytes (E6/E7) were used as the comparison cell line. Our …

The Global Cancer Genomics Consortium's Third Annual Symposium: From Oncogenomics To Cancer Care, Luis Costa, Sandra Casimiro, Sudeep Gupta, Stefan Knapp, M. Radhakrishna Pillai, Mazakazu Toi, Rajendra Badwe, Maria Carmo-Fonesca, Rakesh Kumar

Biochemistry and Molecular Medicine Faculty Publications

The Global Cancer Genomics Consortium (GCGC) is a cohesive network of oncologists, cancer biologists and structural and genomics experts residing in six institutions from Lisbon, United Kingdom, Japan, India, and United States. The team is using its combined resources and infrastructures to address carefully selected, shared, burning questions in cancer medicine. The Third Annual Symposium was organized by the Institute of Molecular Medicine, Lisbon Medical School, Lisbon, Portugal, from September 18 to 20, 2013. To highlight the benefits and limitations of recent advances in cancer genomics, the meeting focused on how to better translate our gains in oncogenomics to cancer …

Role Of Hepatitis C Virus Inducted Osteopontin In Epithelial To Mesenchymal Transition, Migration, And Invasion Of Hepatocytes, Jawed Iqbal, Steven Mcrae, Thi Mai, Krishna Banaudha, Mehuli Sarkar-Dutta, Gulam Waris

Biochemistry and Molecular Medicine Faculty Publications

Osteopontin (OPN) is a secreted phosphoprotein which has been linked to tumor progression and metastasis in a variety of cancers including hepatocellular carcinoma (HCC). Previous studies have shown that OPN is upregulated during liver injury and inflammation. However, the role of OPN in hepatitis C virus (HCV)-induced liver disease pathogenesis is not known. In this study, we determined the induction of OPN, and then investigated the effect of secreted forms of OPN in epithelial to mesenchymal transition (EMT), migration and invasion of hepatocytes. We show the induction of OPN mRNA and protein expression by HCV-infection. Our results also demonstrate the …

Non-Synonymous Variations In Cancer And Their Effects On The Human Proteome: Workflow For Ngs Data Biocuration And Proteome-Wide Analysis Of Tcga Data, Charles Cole, Konstantinos Krampis, Konstantinos Karagiannis, Jonas Almeida, William J. Faison, Mona Motwani, Quan Wan, Anton Golikov, Yang Pan, Vahan Simonyan, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

Background

Next-generation sequencing (NGS) technologies have resulted in petabytes of scattered data, decentralized in archives, databases and sometimes in isolated hard-disks which are inaccessible for browsing and analysis. It is expected that curated secondary databases will help organize some of this Big Data thereby allowing users better navigate, search and compute on it.

Results

To address the above challenge, we have implemented a NGS biocuration workflow and are analyzing short read sequences and associated metadata from cancer patients to better understand the human variome. Curation of variation and other related information from control (normal tissue) and case (tumor) samples will …

Understanding The Mechanism Of Glucose-Induced Relief Of Rgt1-Mediated Repression In Yeast, Adhiraj Roy, David Jouandot, Kyu Hong Cho, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

The yeast Rgt1 repressor inhibits transcription of the glucose transporter (HXT) genes in the absence of glucose. It does so by recruiting the general corepressor complex Ssn6-Tup1 and the HXT corepressor Mth1. In the presence of glucose, Rgt1 is phosphorylated by the cAMP-activated protein kinase A (PKA) and dissociates from the HXT promoters, resulting in expression of HXT genes. In this study, using Rgt1 chimeras that bind DNA constitutively, we investigate how glucose regulates Rgt1 function. Our results show that the DNA-bound Rgt1 constructs repress expression of the HXT1 gene in conjunction with Ssn6-Tup1 and Mth1, and that …

A Framework For Organizing Cancer-Related Variations From Existing Databases, Publications And Ngs Data Using A High-Performance Integrated Virtual Environment (Hive), Tsung-Jung Wu, Amirhossein Shamsaddini, Yang Pan, Krista Smith, Daniel J. Chrichton, Vahan Simonyan, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

Years of sequence feature curation by UniProtKB/Swiss-Prot, PIR-PSD, NCBI-CDD, RefSeq and other database biocurators has led to a rich repository of information on functional sites of genes and proteins. This information along with variation-related annotation can be used to scan human short sequence reads from next-generation sequencing (NGS) pipelines for presence of non-synonymous single-nucleotide variations (nsSNVs) that affect functional sites. This and similar workflows are becoming more important because thousands of NGS data sets are being made available through projects such as The Cancer Genome Atlas (TCGA), and researchers want to evaluate their biomarkers in genomic data. BioMuta, an integrated …

Alpha-Asarone Protects Endothelial Cells From Injury By Angiotensin Ii, Ha-Xia Shi, Jiajun Yang, Tao Yang, Yong-Liang Xue, Jun Liu, Ya-Juan Li, Dan-Dan Zhang, Ji-Wen Zhu, Ka Bian

Biochemistry and Molecular Medicine Faculty Publications

α-Asarone is the major therapeutical constituent of Acorus tatarinowii Schott. In this study, the potential protective effects of α-asarone against endothelial cell injury induced by angiotensin II were investigated in vitro. The EA.hy926 cell line derived from human umbilical vein endothelial cells was pretreated with α-asarone (10, 50, 100 µmol/L) for 1 h, followed by coincubation with Ang II (0.1 µmol/L) for 24 h. Intracellular nitric oxide (NO) and reactive oxygen species (ROS) were detected by fluorescent dyes, and phosphorylation of endothelial nitric oxide synthase (eNOS) at was determined by Western blotting. α-Asarone dose-dependently mitigated the Ang II-induced intracellular NO …

High-Performance Integrated Virtual Environment (Hive) Tools And Applications For Big Data Analysis, Vahan Simonyan, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

The High-performance Integrated Virtual Environment (HIVE) is a high-throughput cloud-based infrastructure developed for the storage and analysis of genomic and associated biological data. HIVE consists of a web-accessible interface for authorized users to deposit, retrieve, share, annotate, compute and visualize Next-generation Sequencing (NGS) data in a scalable and highly efficient fashion. The platform contains a distributed storage library and a distributed computational powerhouse linked seamlessly. Resources available through the interface include algorithms, tools and applications developed exclusively for the HIVE platform, as well as commonly used external tools adapted to operate within the parallel architecture of the system. HIVE is …

Single-Nucleotide Variations In Cardiac Arrhythmias: Prospects For Genomics And Proteomics Based Biomarker Discovery And Diagnostics, Ayman Abunimer, Krista Smith, Tsung-Jung Wu, Phuc Lam, Vahan Simonyan, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

Cardiovascular diseases are a large contributor to causes of early death in developed countries. Some of these conditions, such as sudden cardiac death and atrial fibrillation, stem from arrhythmias—a spectrum of conditions with abnormal electrical activity in the heart. Genome-wide association studies can identify single nucleotide variations (SNVs) that may predispose individuals to developing acquired forms of arrhythmias. Through manual curation of published genome-wide association studies, we have collected a comprehensive list of 75 SNVs associated with cardiac arrhythmias. Ten of the SNVs result in amino acid changes and can be used in proteomic-based detection methods. In an effort to …

Census-Based Rapid And Accurate Metagenome Taxonomic Profiling, Amirhossein Shamsaddini, Yang Pan, W. Evan Johnson, Konstantinos Krampis, Mariya Shcheglovitova, Vahan Simonyan, Amy Zanne, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

Background

Understanding the taxonomic composition of a sample, whether from patient, food or environment, is important to several types of studies including pathogen diagnostics, epidemiological studies, biodiversity analysis and food quality regulation. With the decreasing costs of sequencing, metagenomic data is quickly becoming the preferred typed of data for such analysis.

Results

Rapidly defining the taxonomic composition (both taxonomic profile and relative frequency) in a metagenomic sequence dataset is challenging because the task of mapping millions of sequence reads from a metagenomic study to a non-redundant nucleotide database such as the NCBI non-redundant nucleotide database (nt) is a computationally intensive …

Human Germline And Pan-Cancer Variomes And Their Distinct Functional Profiles, Yang Pan, Konstantinos Karagiannis, Haichen Zhang, Hayley Dingerdissen, Amirhossein Shamsaddini, Quan Wan, Vahan Simonyan, Raja Mazumder

Biochemistry and Molecular Medicine Faculty Publications

Identification of non-synonymous single nucleotide variations (nsSNVs) has exponentially increased due to advances in Next-Generation Sequencing technologies. The functional impacts of these variations have been difficult to ascertain because the corresponding knowledge about sequence functional sites is quite fragmented. It is clear that mapping of variations to sequence functional features can help us better understand the pathophysiological role of variations. In this study, we investigated the effect of nsSNVs on more than 17 common types of post-translational modification (PTM) sites, active sites and binding sites. Out of 1 705 285 distinct nsSNVs on 259 216 functional sites we identified 38 …