Cell and Developmental Biology Commons^™

Serum Protein Signatures For Breast Cancer Detection In Treatment-Naïve African American Women Using Integrated Proteomics And Pattern Analysis, Padma Tadi Uppala, Elmer Rivera, Hyun J. Kwon, Sharon S. Lum

Faculty Publications

Breast cancer is the leading cause of cancer-related mortality in African American (AA) women. In this study we evaluated the serum proteomic profile of AA women with breast cancer using an integrated proteomic framework with multivariate pattern analysis. Using 2D-DIGE, thousands of serum protein spots were detected across 33 gels; 46 spots met criteria for presence, statistical significance, and differential expression. Proteins from the spots were identified by MALDI-TOF/TOF and matched in curated databases, highlighting serum biomarkers including ceruloplasmin, alpha-2-macroglobulin, complement component C3 and C6, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein and haptoglobin-related protein. LC-MS/MS analysis revealed 163 differentiating peptides after imputing and …

Adipocyte-Derived Cchamide-1, Eiger, Growth-Blocking Peptide 3, And Unpaired 2 Regulate Drosophila Melanogaster Oogenesis, Chad Simmons, Isaiah Williams, Tancia Bradshaw, Alissa R. Armstrong

Faculty Publications

In addition to energy storage, adipose tissue communication to other organs plays a key role in regulating organismal physiology. While the link between adipose tissue dysfunction and pathophysiology, including diabetes, chronic inflammation, and infertility, is clear, the molecular mechanisms that underlie these associations have not been fully described. We use Drosophila melanogaster as a model to better understand how adipose tissue communicates to the ovary. In this study, we utilized D. melanogaster’s robust genetic toolkit to examine the role of five adipokines known to control larval growth during development, CCHamide-1, CCHamide-2, eiger, Growth-blocking peptide 3, and unpaired 2 in regulating …

Ras/Mapk Signaling Mediates Adipose Tissue Control Of Ovarian Germline Survival And Ovulation In Drosophila Melanogaster, Tancia Bradshaw, Chad Simmons, Rachael Ott, Alissa Richmond Armstrong

Faculty Publications

From insects to humans, oogenesis is tightly linked to nutritional input, yet little is known about how whole organism physiology matches dietary changes with oocyte development. Considering that diet-induced adipose tissue dysfunction is associated with an increased risk for fertility problems, and other obesity-associated pathophysiologies, it is critical to decipher the cellular and molecular mechanisms linking adipose nutrient sensing to remote control of the ovary and other tissues. Our previous studies in Drosophila melanogaster have shown that amino acid sensing, via the amino acid response pathway and mTOR-mediated signaling function within adipocytes to control germline stem cell maintenance and ovulation, …

Integrating Clinical Cancer And Ptm Proteomics Data Identifies A Mechanism Of Ack1 Kinase Activation, Eranga R. Balasooriya, Deshan Madhusanka, Tania P. López-Palacios, Riley J. Eastmond, Dasun Jayatunge, Jake J. Owen, Jack S. Gashler, Christina M. Egbert, Chanaka Bulathsinghalage, Lu Liu, Stephen R. Piccolo, Joshua L. Andersen

Faculty Publications

Beyond the most common oncogenes activated by mutation (mut-drivers), there likely exists a variety of low-frequency mut-drivers, each of which is a possible frontier for targeted therapy. To identify new and understudied mut-drivers, we developed a machine learning (ML) model that integrates curated clinical cancer data and posttranslational modification (PTM) proteomics databases. We applied the approach to 62,746 patient cancers spanning 84 cancer types and predicted 3,964 oncogenic mutations across 1,148 genes, many of which disrupt PTMs of known and unknown function. The list of putative mut-drivers includes established drivers and others with poorly understood roles in cancer. This ML …

Appendage Abnormalities In Spiders Induced By An Alternating Temperature Protocol In The Context Of Recent Advances In Molecular Spider Embryology, Teresa Napiorkowska, Julita Templin, Pawel Napiorkowski, Mark A. Townley

Faculty Publications

In the literature there are numerous reports of developmental deformities in arthropods collected in their natural habitat. Since such teratogenically affected individuals are found purely by chance, the causes of their defects are unknown. Numerous potential physical, mechanical, chemical, and biological teratogens have been considered and tested in the laboratory. Thermal shocks, frequently used in teratological research on the spider Eratigena atrica, have led to deformities on both the prosoma and the opisthosoma. In the 2020/2021 breeding season, by applying alternating temperatures (14 °C and 32 °C, changed every 12 h) for the first 10 days of embryonic development, …

Murine Trophoblast Stem Cells And Their Differentiated Cells Attenuate Zika Virus In Vitro By Reducing Glycosylation Of The Viral Envelope Protein, Biswas Neupane, Mona Fendereski, Farzana Nazneen, Yanlin Guo, Fengwei Bai

Faculty Publications

Zika virus (ZIKV) infection during pregnancy can cause devastating fetal neuropathological abnormalities, including microcephaly. Most studies of ZIKV infection in pregnancy have focused on post-implantation stage embryos. Currently, we have limited knowledge about how a pre-implantation stage embryo deals with a viral infection. This study investigates ZIKV infection on mouse trophoblast stem cells (TSCs) and their in vitro differentiated TSCs (DTSCs), which resemble the cellular components of the trophectoderm layer of the blastocyst that later develops into the placenta. We demonstrate that TSCs and DTSCs are permissive to ZIKV infection; however, ZIKV propagated in TSCs and DTSCs exhibit substantially lower …

Toward A Methodology For Evaluating Dna Variants In Nuclear Families, Dustin B. Miller, Reid Robison, Stephen Piccolo

Faculty Publications

The genetic underpinnings of most pediatric-cancer cases are unknown. Population-based studies use large sample sizes but have accounted for only a small proportion of the estimated heritability of pediatric cancers. Pedigree-based studies are infeasible for most human populations. One alternative is to collect genetic data from a single nuclear family and use inheritance patterns within the family to filter candidate variants. This approach can be applied to common and rare variants, including those that are private to a given family or to an affected individual. We evaluated this approach using genetic data from three nuclear families with 5, 4, and …

Predicting Drug Sensitivity Of Cancer Cells Based On Dna Methylation Levels, Sofia P. Miranda, Fernanda A. Baião, Julia L. Fleck, Stephen R. Piccolo

Faculty Publications

Cancer cell lines, which are cell cultures derived from tumor samples, represent one of the least expensive and most studied preclinical models for drug development. Accurately predicting drug responses for a given cell line based on molecular features may help to optimize drug-development pipelines and explain mechanisms behind treatment responses. In this study, we focus on DNA methylation profiles as one type of molecular feature that is known to drive tumorigenesis and modulate treatment responses. Using genome-wide, DNA methylation profiles from 987 cell lines in the Genomics of Drug Sensitivity in Cancer database, we used machine-learning algorithms to evaluate the …

A Systematic Review Of Datasets That Can Help Elucidate Relationships Among Gene Expression, Race, And Immunohistochemistry-Defined Subtypes In Breast Cancer., Ifeanyichukwu O. Nwosu, Stephen Piccolo

Faculty Publications

Scholarly requirements have led to a massive increase of transcriptomic data in the public domain, with millions of samples available for secondary research. We identified gene-expression datasets representing 10,214 breast-cancer patients in public databases. We focused on datasets that included patient metadata on race and/or immunohistochemistry (IHC) profiling of the ER, PR, and HER-2 proteins. This review provides a summary of these datasets and describes findings from 32 research articles associated with the datasets. These studies have helped to elucidate relationships between IHC, race, and/or treatment options, as well as relationships between IHC status and the breast-cancer intrinsic subtypes. We …

Topsentinol L Trisulfate, A Marine Natural Product That Targets Basal-Like And Claudin-Low Breast Cancers, Nader N. El-Chaar, Thomas E. Smith, Gajendra Shrestha, Stephen R. Piccolo, Mary Kay Harper, Ryan M. Van Wagoner, Zhenyu Lu, Ashlee R. Venancio, Chris M. Ireland, Andrea H. Bild, Philip J. Moos

Faculty Publications

Patients diagnosed with basal-like breast cancer suffer from poor prognosis and limited treatment options. There is an urgent need to identify new targets that can benefit patients with basal-like and claudin-low (BL-CL) breast cancers. We screened fractions from our Marine Invertebrate Compound Library (MICL) to identify compounds that specifically target BL-CL breast cancers. We identified a previously unreported trisulfated sterol, i.e., topsentinol L trisulfate (TLT), which exhibited increased efficacy against BL-CL breast cancers relative to luminal/HER2+ breast cancer. Biochemical investigation of the effects of TLT on BL-CL cell lines revealed its ability to inhibit activation of AMP-activated protein kinase (AMPK) …

Propranolol Sensitizes Vascular Sarcoma Cells To Doxorubicin By Altering Lysosomal Drug Sequestration And Drug Efflux, Jhuma Saha, Jong Hyuk Kim, Clarissa N. Amaya, Caleb M. Witcher, Ali Khammanivong, Derek M. Korpela, David R. Brown, Josephine Taylor, Brad A. Bryan, Erin B. Dickerson

Faculty Publications

Angiosarcoma is a rare cancer of blood vessel–forming cells with a high patient mortality and few treatment options. Although chemotherapy often produces initial clinical responses, outcomes remain poor, largely due to the development of drug resistance. We previously identified a subset of doxorubicin-resistant cells in human angiosarcoma and canine hemangiosarcoma cell lines that exhibit high lysosomal accumulation of doxorubicin. Hydrophobic, weak base chemotherapeutics, like doxorubicin, are known to sequester within lysosomes, promoting resistance by limiting drug accessibility to cellular targets. Drug synergy between the beta adrenergic receptor (β-AR) antagonist, propranolol, and multiple chemotherapeutics has been documented in vitro, and …

Biochemical And Genetic Analysis Of Ecm14, A Conserved Fungal Pseudopeptidase, R. Christian Mcdonald, Matthew James Schott, Temitope A. Idowu, Peter J. Lyons

Faculty Publications

© 2020, The Author(s). Background: Like most major enzyme families, the M14 family of metallocarboxypeptidases (MCPs) contains a number of pseudoenzymes predicted to lack enzyme activity and with poorly characterized molecular function. The genome of the yeast Saccharomyces cerevisiae encodes one member of the M14 MCP family, a pseudoenzyme named Ecm14 proposed to function in the extracellular matrix. In order to better understand the function of such pseudoenzymes, we studied the structure and function of Ecm14 in S. cerevisiae. Results: A phylogenetic analysis of Ecm14 in fungi found it to be conserved throughout the ascomycete phylum, with a group of …

Comparative Efficacies Of Calmare Therapy And Transcutaneous Electrical Nerve Stimulation In Randomized Peripheral Neuropathy Subjects With Resting State Fmri Monitoring, Ty A. Bodily, Logan Edvalson, Jordan B. Peacock, Zack M. Bradshaw, Carson Hart, Cameron Ernst, Samuel Biggs, David D. Busath

Faculty Publications

Clinical reports of Calmare protocol efficacy suggest enhanced durability compared to TENS and the possibility changes in resting fMRI connectivity. The objective was to compare peripheral neuropathy pain relief and resting fMRI changes with Calmare and TENS treatments. Randomized double-blind trials performed in August 2015 and between August 2016 and November 2017, with 18 and 20 human peripheral neuropathy subjects, respectively. The initial trial examined effects of a single session while the latter trial examined the effects of a course of ten treatment sessions on consecutive weekdays. fMRI scans were examined for changes in blood flow correlations and connectivity. Subjective …

Cysteine Dioxygenase Enzyme Activity And Gene Expression In The Dimorphic Pathogenic Fungus Histoplasma Capsulatum Is In Both The Mold And Yeast Morphotypes And Exhibits Substantial Strain Variation, Melissa Adams, Glen Shearer

Faculty Publications

In the dimorphism (mold/yeast) Histoplasma capsulatum (Hc) literature are reports that yeast (the so-called pathogenic form) uniquely expresses a cysteine dioxygenase (CDO, approx. 10,500 dal) activity which the mold morphotype (the so-called saprophytic soil form) does not express (C.F., Kumar et al., Biochem 22, 762, 1983). This yeast-specific CDO activity is postulated to play a critical role in the mold-to-yeast shift. A number of years ago, our lab isolated the gene encoding the Hc cysteine dioxygenase (CDO1, Genbank accession AY804144) and noted significant expression in the mold morphotype of several Histoplasma strains and also determined that the predicted protein would …

Functional And Transcriptomic Characterization Of Cisplatin-Resistant Ags And Mkn-28 Gastric Cancer Cell Lines, Barbara Mora-Lagos, Irene Cartas-Espinel, Ismael Riquelme, Alyssa C. Parker, Stephen R. Piccolo, Tamara Viscarra, Maria Elena Reyes, Louise Zanella, Kurt Buchegger, Carmen Ili, Priscilla Brebi

Faculty Publications

Gastric cancer (GC) is a significant cancer-related cause of death worldwide. The most used chemotherapeutic regimen in GC is based on platinum drugs such as cisplatin (CDDP). However, CDDP resistance reduces advanced GC survival. In vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize new models of CDDP-resistant GC cell lines (AGS R-CDDP and MKN-28 R-CDDP) obtained through a stepwise increasing drug doses method, in order to understand the molecular mechanisms underlying chemoresistance as well as identify new therapeutic targets for the treatment of GC. …

Functional And Transcriptomic Characterization Of Carboplatin-Resistant A2780 Ovarian Cancer Cell Line, Tamara Viscarra, Kurt Buchegger, Ignacio Jofre, Ismael Riquelme, Louise Zanella, Michel Abanto, Alyssa C. Parker, Stephen R. Piccolo, Juan Carlos Roa, Carmen Ili, Priscilla Brebi

Faculty Publications

Background

Ovarian cancer is a significant cancer-related cause of death in women worldwide. The most used chemotherapeutic regimen is based on carboplatin (CBDCA). However, CBDCA resistance is the main obstacle to a better prognosis. An in vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize cellular and molecular changes of induced CBDCA-resistant ovarian cancer cell line A2780.

Methods

The cell selection strategy used in this study was a dose-per-pulse method using a concentration of 100 μM for 2 h. Once 20 cycles of exposure to …

Does Family Communication Matter? Exploring Knowledge Of Breast Cancer Genetics In Cancer Families, Deborah Himes, Sarah H. Davis, Jane Lassetter Phd, Rn, Neil E. Peterson, Margaret F. Clayton, Wendy C. Birmingham, Anita Y. Kinney

Faculty Publications

Purpose: Knowledge of breast cancer genetics is critical for those at increased hereditary risk who must make decisions about breast cancer screening options. This descriptive study explored theory-based relationships among cognitive and emotional variables related to knowledge of breast cancer genetics in cancer families. Methods: Participants included first-degree relatives of women with breast cancer who had received genetic counseling and testing. Study participants themselves did not have breast cancer and had not received genetic counseling or testing. Data were collected by telephone interviews and surveys. Variables analyzed included numeracy, health literacy, cancer-related distress, age, education, and the reported amount of …

Characterization Of Embyronic Stem Cell-Differentiated Fibroblasts As Mesenchymal Stem Cells With Robust Expansion Capacity And Attenuated Innate Immunity, William D'Angelo, Bohan Chen, Chandan Gurung, Yan-Lin Guo

Faculty Publications

Background: Mesenchymal stem cells (MSCs) isolated from adult tissues (Ad-MSCs) have shown great promise for use in regenerative medicine. However, their poor in vitro expansion capacity and tissue scarcity have been major limitations. In this study, we demonstrate that mouse embryonic stem cells (mESCs) can differentiate into cells with MSC properties.

Methods: Using previously established methods that characterize Ad-MSCs, we analyzed mESC-differentiated fibroblasts (mESC-FBs), including plastic adherence, clonogenic growth, MSC marker expression, tri-lineage differentiation potential, and the capacity to express immunomodulators.

Results: Although previously characterized as mESC-differentiated fibroblasts (mESC-FBs), these cells exhibit major properties of Ad-MSCs. However, …

Membrane Expression Of Thymidine Kinase 1 And Potential Clinical Relevance In Lung, Breast, And Colorectal Malignancies, Evita G. Weagel, Weston Burrup, Roman Kovtun, Edwin J. Valazquez, Abigail M. Felsted, Michelle H. Townsend, Zachary E. Ence, Erica Suh, Stephen Piccolo, K. Scott Weber, Richard A. Robison, Kim Oneill

Faculty Publications

Background: Lung, breast, and colorectal malignancies are the leading cause of cancer-related deaths in the world causing over 2.8 million cancer-related deaths yearly. Despite efforts to improve prevention methods, early detection, and treatments, survival rates for advanced stage lung, breast, and colon cancer remain low, indicating a critical need to identify cancer-specific biomarkers for early detection and treatment. Thymidine kinase 1 (TK1) is a nucleotide salvage pathway enzyme involved in cellular proliferation and considered an important tumor proliferation biomarker in the serum. In this study, we further characterized TK1’s potential as a tumor biomarker and immunotherapeutic target and clinical relevance. …

Diverse Exocytic Pathways For Mast Cell Mediators, Hao Xu, Na-Ryum Bin, Shuzo Sugita

Faculty Publications

Mast cells play pivotal roles in innate and adaptive immunities but are also culprits in allergy, autoimmunity and cardiovascular diseases. Mast cells respond environmental changes by initiating regulated exocytosis/secretion of various biologically active compounds called mediators (e.g., proteases, amines and cytokines). Many of these mediators are stored in granules/lysosomes and rely on an intricate degranulation process for release. Mast cell stabilizers (such as sodium cromoglicate) which prevent such degranulation process have therefore been clinically approved to treat asthma and allergic rhinitis. However, it has become increasingly clear that different mast cell diseases often involve multiple mediators, which seem to rely …

Pkc-Dependent Phosphorylation Of Munc18a At Ser313 In Activated Rbl-2h3 Cells, Pratikshya Adhikari, Hao Xu

Faculty Publications

Protein Kinase C (PKC) regulates the release of pro-inflammatory compounds from IgE/antigen-activated mast cells by unknown mechanisms. In this study, we show for the first time that PKC inhibitor Ro-03-0432, which inhibits RBL-2H3 exocytosis/degranulation in a concentration-dependent fashion, prevents the phosphorylation of membrane fusion factor Munc18a at Ser 313. Our study provides fresh evidence that PKC-dependent protein phosphorylation may contribute to the intricate regulation of mast cell degranulation by directly targeting the fusion factors.

An Undergraduate Laboratory Manual For Analyzing A Crispr Mutant With A Predicted Role In Regeneration, Susan Walsh, Ashley Becker, Paxton S. Sickler, Damian G. Clarke, Erin Jimenez

Faculty Publications

Exposing students to undergraduate research has reportedly improved students’ development of knowledge and skills in the laboratory, self-efficacy, satisfaction with their research, retention, and perseverance when faced with obstacles. Furthermore, utilizing authentic course-based undergraduate research experiences (CUREs) includes all students enrolled in the class, giving those who may not otherwise have access to an independent undergraduate research project an opportunity to engage in the scientific process in context of an original, unanswered question. In the fall of 2016, second semester introductory biology students conducted a semester-long research project on the transcription factor Lin28a to determine the effect of Lin28a on …

Combating Subclonal Evolution Of Resistant Cancer Phenotypes, Samuel W. Brady, Jasmine A. Mcquerry, Yi Qiao, Stephen Piccolo, Gajendra Shrestha, David F. Jenkins, Ryan M. Layer, Brent S. Pedersen, Ryan H. Miller, Amanda Esch, Sara R. Selitsky, Joel S. Parker, Layla A. Anderson, Brian K. Dalley, Rachel E. Factor, Chakravarthy B. Reddy, Jonathan P. Boltax, Dean Li, Philip J. Moos, Joe W. Gray, Laura M. Heiser, Saundra S. Buys, Adam L. Cohen, W. Evan Johnson, Aaron R. Quinlan, Gabor Marth, Theresa L. Werner, Andrea H. Bild

Faculty Publications

Metastatic breast cancer remains challenging to treat, and most patients ultimately progress on therapy. This acquired drug resistance is largely due to drug-refractory sub-populations (subclones) within heterogeneous tumors. Here, we track the genetic and phenotypic subclonal evolution of four breast cancers through years of treatment to better understand how breast cancers become drug-resistant. Recurrently appearing post-chemotherapy mutations are rare. However, bulk and single-cell RNA sequencing reveal acquisition of malignant phenotypes after treatment, including enhanced mesenchymal and growth factor signaling, which may promote drug resistance, and decreased antigen presentation and TNF-α signaling, which may enable immune system avoidance. Some of these …

Novel Species-Specific Glycoprotein On The Surface Of Mytilus Edulis And M. Trossulus Eggs, Fiona M. Harper, Kasandra J. Riley, R. D. Rawson

Faculty Publications

Protein–protein interactions play a central role in the gamete attraction, binding, and fusion stages of gamete interactions and fertilization for broadcast spawning species, such as marine mussels in the Mytilus edulis species complex. Although assortative gamete interaction has been implicated in the level of reproductive isolation among the three species in this complex, the molecular basis of these interactions has not been elucidated. Using mass spectrometry peptide sequencing, cDNA sequencing, and bioinformatics approaches, we have investigated species-level variation in the proteins expressed on the surface of mussel eggs. We herein describe an extracellular protein, MESP-1, from the surface of the …

Small Grants Make A Big Difference, Susan Walsh

Faculty Publications

No abstract provided.

Utilization Of Different Anti-Viral Mechanisms By Mammalian Embryonic Stem Cells And Differentiated Cells, Yan-Lin Guo

Faculty Publications

Embryonic stem cells (ESCs) have received tremendous attention because of their potential applications in regenerative medicine. Over the past two decades, intensive research has not only led to the generation of various types of cells from ESCs that can be potentially used for the treatment of human diseases but also led to the formation of new concepts and breakthroughs that have significantly impacted our understanding of basic cell biology and developmental biology. Recent studies have revealed that ESCs and other types of pluripotent cells do not have a functional interferon (IFN)-based anti-viral mechanism, challenging the idea that the IFN system …

A Cloud-Based Workflow To Quantify Transcript-Expression Levels In Public Cancer Compendia, P J. Tatlow, Stephen R. Piccolo

Faculty Publications

Public compendia of sequencing data are now measured in petabytes. Accordingly, it is infeasible for researchers to transfer these data to local computers. Recently, the National Cancer Institute began exploring opportunities to work with molecular data in cloud-computing environments. With this approach, it becomes possible for scientists to take their tools to the data and thereby avoid large data transfers. It also becomes feasible to scale computing resources to the needs of a given analysis. We quantified transcript-expression levels for 12,307 RNA-Sequencing samples from the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas. We used two cloud-based configurations and …

Characterization Of The Three Zebrafish Orthologs Of The Mitochondrial Gtpase Miro/Rhot, Brittany M. Hollister, Kelsey A. Oonk, Douglas C. Weiser, Susan Walsh

Faculty Publications

Mitochondria exhibit dynamic locomotion and spatial rearrangement. This movement is necessary for a cell to maintain basic metabolic functions, and disruption of motility often results in cell death. Miro is a mitochondrial outer membrane Rho GTPase essential for mitochondrial movement and distribution in diverse systems, including yeast, animals, and plants. We sought to study the previously uncharacterized Miro protein family in zebrafish. We confirmed that, like human Miro, the zebrafish Miro proteins (Rhot1a, Rhot1b, and Rhot2) localize to mitochondria in mammalian tissue culture cells by both biochemical fractionation and immunofluorescent colocalization. In addition, using whole mount in situ hybridization, we …

Assign: Context-Specific Genomic Profiling Of Multiple Heterogeneous Biological Pathways, Ying Shen, Mumtahena Rahman, Stephen R. Piccolo, Daniel Gusenleitner, Nader N. El-Chaar, Luis Cheng, Stefano Monti, Andrea H. Bild, W. Evan Johnson

Faculty Publications

Motivation: Although gene-expression signature-based biomarkers are often developed for clinical diagnosis, many promising signatures fail to replicate during validation. One major challenge is that biological samples used to generate and validate the signature are often from heterogeneous biological contexts—controlled or in vitro samples may be used to generate the signature, but patient samples may be used for validation. In addition, systematic technical biases from multiple genome-profiling platforms often mask true biological variation. Addressing such challenges will enable us to better elucidate disease mechanisms and provide improved guidance for personalized therapeutics.

Results: Here, we present a pathway profiling toolkit, Adaptive Signature …

Robust Meta-Analysis Shows That Glioma Transcriptional Subtyping Complements Traditional Approaches, Sanghoon Lee, Stephen Piccolo, Kristina Allen-Brady

Faculty Publications

Background Gliomas traditionally have been sub-classified
based on histopathological observations. However, this ap-
proach is subject to inter-observer variability, and histopatho-
logical features may not reflect the biological mechanisms that
drive tumor growth. High-throughput transcriptional profiling
has shown promise in objectively and reproducibly identify-
ing glioma subtypes. Most prior studies have typically used
only modest sample sizes and have sometimes overlooked
important data-processing steps to ensure sample quality and
to evaluate the robustness of quantitative findings. The pur-
pose of our study was to define robust glioma subtypes by
applying rigorous preprocessing and validation steps to 1,952
microarray samples aggregated …