bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1666: Developing healthcare data scientists using Veterans Health Administration (VHA) data resources: The NCI/VA Big Data Scientist Training Enhancement Program (BD-STEP)
Authors: Elder Sarah G. , Berny-Lang Michelle 
Published: August 2019

Abstract
Due to advances in molecular profiling and medical imaging and the increased adoption of electronic health records (EHRs), the growth in oncology-related data has surpassed the development of a workforce capable of analyzing these data. This marks a missed opportunity in cancer research to gain insights toward better prediction of disease risk and therapeutic response. The Big Data Scientist Training Enhancement Program (BD-STEP), jointly managed by the National Cancer Institute and the Veterans Health Administration, addresses this gap by training the next generation of healthcare data scientists using the VA’s healthcare data infrastructure. Post-doctoral fellows from science and engineering backgrounds are paired with VA medical centers across the country, where they are immersed in the clinical environment as they pursue high-impact clinical research questions through data science. They enrich their data science skills using VA data resources, including clinical data from the VA healthcare system, genomic data from the Million Veterans Program (MVP), and treatment and diagnosis data from the VA Central Cancer Registry. Prospective fellows, data science experts, and healthcare researchers are encouraged to learn more about the program, its training opportunities, and existing projects using VA healthcare data.
Citation Format: Sarah G. Elder, Michelle Berny-Lang. Developing healthcare data scientists using Veterans Health Administration (VHA) data resources: The NCI/VA Big Data Scientist Training Enhancement Program (BD-STEP) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1666.
Abstract 1667: A robust human immune profiling assay using CyTOF technology and automated data analysis software
Authors: Li Stephen K. , Majonis Daniel , Bagwell C. Bruce , Hunsberger Benjamin C. , Baranov Vladimir I. , Ornatsky Olga I. 
Published: August 2019

Abstract
Immune monitoring is an essential method for quantifying changes in immune cell population numbers and states over time in health and disease. A cornerstone in translational and clinical research, it is frequently used in the investigation of chronic inflammation, infectious disease, autoimmune diseases, and cancer. The diversity of immune cell populations demands a highparameter approach to more fully and efficiently quantify these changes. Mass cytometry, which utilizes CyTOF® technology, is a single-cell analysis platform that uses metal-tagged antibodies to resolve over 40 markers in a single tube of sample without the need for compensation. It is an ideal solution for routine enumeration of immune cell populations. However, development of a robust, highly multiplexed assay requires panel optimization as well as standardization of instrument setup and an analysis pipeline.
We have developed a sample-to-answer solution for human immune profiling using mass cytometry. It includes an optimized 30-marker immune profiling panel provided in a lyophilized, single-tube format, validated SOPs for human whole blood and PBMC staining, an instrument data acquisition template, instructions for data acquisition on a Helios™ system, and automated software for data analysis. The software analyzes FCS 3.0 files generated with the kit; automatically reports cell counts, percentage calculations, and staining intensity; and produces graphical elements such as histograms, dot plots, and a Cen-se′™ (t-SNE variant) graph for 36 immune cell populations.
Here we present assay analytical validation data on repeatability, reproducibility, software precision, and software accuracy. We also present a performance comparison of the lyophilized material and a liquid formulation of the same antibodies and clones used in the lyophilized format. This assay provides a robust, complete solution for broad immune profiling using mass cytometry that reduces sources of variability and subjectivity in sample preparation and data analysis.
Citation Format: Stephen K. Li, Daniel Majonis, C. Bruce Bagwell, Benjamin C. Hunsberger, Vladimir I. Baranov, Olga I. Ornatsky. A robust human immune profiling assay using CyTOF technology and automated data analysis software [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1667.
Abstract 1669: Full length transcriptome sequencing of melanoma cell line complements long read sequencing assessment of genomic rearrangements
Authors: Tseng Elizabeth , Galvin Brendan , Hon Ting , Kloosterman Wigard P. , Ashby Meredith 
Published: August 2019

Abstract
Transcriptome sequencing has proven to be an important tool for understanding the biological changes in cancer genomes including the consequences of structural rearrangements. Short read sequencing has been the method of choice, as the high throughput at low cost allows for transcript quantitation and the detection of even rare transcripts. However, the reads are generally too short to reconstruct complete isoforms. Conversely, long-read approaches can provide unambiguous full-length isoforms, but lower throughput has complicated quantitation and high RNA input requirements has made working with cancer samples challenging.
Recently, the COLO 829 cell line was sequenced to 50-fold coverage with PacBio SMRT Sequencing. To validate and extend the findings from this effort, we have generated long-read transcriptome data using an updated PacBio Iso-Seq method, the results of which will be shared at the AACR 2019 General Meeting. With this complimentary transcriptome data, we demonstrate how recent innovations in the PacBio Iso-Seq method sample preparation and sequencing chemistry have made long-read sequencing of cancer transcriptomes more practical. In particular, library preparation has been simplified and throughput has increased. The improved protocol has reduced sample prep time from several days to one day while reducing the sample input requirements ten-fold. In addition, the incorporation of unique molecular identifier (UMI) tags into the workflow has improved the bioinformatics analysis. Yield has also increased, with v3 sequencing chemistry typically delivering &gt; 30 Gb per SMRT Cell 1M. By integrating long and short read data, we demonstrate that the Iso-Seq method is a practical tool for annotating cancer genomes with high-quality transcript information.
Citation Format: Elizabeth Tseng, Brendan Galvin, Ting Hon, Wigard P. Kloosterman, Meredith Ashby. Full length transcriptome sequencing of melanoma cell line complements long read sequencing assessment of genomic rearrangements [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1669.
Abstract 170: Loss of the ubiquitin-specific peptidase 18 (USP18) reduces lung cancer metastasis
Authors: Chen Zibo , Zheng Lin , Chen Yulong , Kawakami Masanori , Mustachio Lisa , Roszik Jason , Liu Xin , Kurie Jonathan , Liu Xi , Dmitrovsky Ethan 
Published: August 2019

Abstract
Metastasis is a major cause of cancer-related mortality. Yet, current antineoplastic strategies do not effectively repress metastasis. Thus, there is a pressing need to explore targets that can reduce metastasis, especially in lung cancer that is the most common cause of cancer mortality. Our prior work reported that expression of the ubiquitin-specific peptidase 18 (USP18) was augmented in diverse cancers (including lung cancers) and USP18 knock-down suppressed in vitro and in vivo growth of murine and human lung cancers. This deubiquitinase stabilizes target proteins by removing interferon-stimulated gene 15 (ISG15) from substrate proteins. We explored here whether engineered loss of USP18 decreased lung cancer metastasis. Stable USP18 knockdown was independently achieved in human (A549 and H1299) and murine (344SQ and KC2) lung cancer cells by use of small hairpin RNAs (shRNAs). Notably, knockdown of USP18 expression reduced lung cancer cellular proliferation, migration and invasion versus control shRNA transfectants (p &lt; 0.001). Lung cancer cells selected for high metastatic potential (344SQ and KC2) were independently injected via tail vein or subcutaneously to establish metastatic mouse models. USP18 knockdown statistically-significantly decreased lung cancer metastases as compared to control shRNA transfectants. To elucidate engaged mechanisms, Reverse Phase Protein Array (RPPA) analysis was performed to interrogate over 300 growth-regulatory proteins in human (A549 and H1299) and murine (344SQ and KC2) lung cancer cells having engineered USP18 knockdown. Results were compared to control shRNA transfectants. Ingenuity pathway analysis highlighted fatty acid synthase (FASN) as a potential USP18 target that regulated lung cancer metastasis. Independent immunoblot analysis confirmed FASN expression was reduced in cancers once USP18 knockdown was achieved. Functional validation of FASN in lung metastasis is underway. These and other findings that will be presented provide a strong rationale for targeting the deubiquitinase USP18 to reduce lung cancer metastasis and combat lung cancers.
Citation Format: Zibo Chen, Lin Zheng, Yulong Chen, Masanori Kawakami, Lisa Mustachio, Jason Roszik, Xin Liu, Jonathan Kurie, Xi Liu, Ethan Dmitrovsky. Loss of the ubiquitin-specific peptidase 18 (USP18) reduces lung cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 170.
Abstract 1701: Improvement of tumor mutation burden measurement by removal of deaminated bases in FFPE DNA
Authors: Tom Warren , Chaudhary Ruchi , Mittal Vinay , Cyanam Dinesh , Casuga Iris , Wong-Ho Elaine , Bennett Rob , Hyland Fiona , Sadis Seth , Au-Young Janice 
Published: August 2019

Abstract
Tumor mutation burden (TMB) is a positive predictive factor for response to immune-checkpoint inhibitors in certain types of cancer. The Oncomine™ Tumor Mutation Load Assay, a 1.7Mb targeted next generation sequencing (NGS) panel, measures TMB and detects mutations in 409 cancer genes. The TMB values obtained using targeted sequencing are positively correlated with TMB measured by whole exome sequencing in NSCLC, colorectal, endometrial and gastric cancers. TMB from these tumor samples are correlated with other phenotypes associated with genomic instability, specifically microsatellite instability (MSI) and mutations involved in mismatch repair and cancer related genes. Analysis of the Oncomine™ TML Assay results with Torrent Suite and Ion Reporter software uniquely measures the degree of deamination of cytosines to uracils in fixed tissues. FFPE preservation methods can lead to significant cytosine deamination of the isolated DNA, resulting in decreased sequencing quality. In these samples, uracils are propagated as thymines and result in false C&gt;T substitutions. To minimize the influence that excess deamination has on TMB results, we have incorporated a UDG enzyme treatment to eliminate damaged targets and improve usable TMB values of DNA from damaged FFPE tumor tissue. The Oncomine™ TML assay for TMB on Ion GeneStudio™ S5 in conjunction with MSI detection is informative and potentially predictive for the use of checkpoint inhibitors in multiple cancer types.
Citation Format: Warren Tom, Ruchi Chaudhary, Vinay Mittal, Dinesh Cyanam, Iris Casuga, Elaine Wong-Ho, Rob Bennett, Fiona Hyland, Seth Sadis, Janice Au-Young. Improvement of tumor mutation burden measurement by removal of deaminated bases in FFPE DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1701.
Abstract 1703: New genetic variations discovered in KRAS wild-type cetuximab resistant Chinese colorectal cancer patients
Authors: Jing Changwen , Wang Ting , Ma Rong , Cao Haixia , Xu EnShun , Wang Zhuo , Liu Siwen , Chen Dan , Zhang Junying , Wu Yang , Zhang Yuan , Ding Ping , Sha Michael Y. , Wu Jianzhong , Feng Jifeng 
Published: August 2019

Abstract
The efficacy of Cetuximab therapy in colorectal cancer patients is limited by the development of therapeutic resistance. The currently known oncogenic ‘driver’ mutations do not fully explain the resistance mechanism of Cetuximab. Currently there are no reports of any studies that have explored new driver mutations in Cetuximab resistance by whole exome sequencing (WES).
In this study, we performed WES to identify common genetic factors from twenty-two Cetuximab-sensitive and ten Cetuximab-resistant patients, aiming to discover characteristic genes associated with Cetuximab resistance. For Cetuximab-sensitive patients, the mutation frequency of MUC16, FCGBP, DMBT1 was found to be 100%, 90.91% and 86.36%, respectively. MUC16, PDE4DIP and TACC2 were altered in all 10 Cetuximab-resistant samples. We also discovered there are 151 significantly mutated genes (SMGs) in Cetuximab sensitive group and 37 in the resistant group. CYP4A11 was the most frequently mutated gene in Cetuximab-resistant patients. BCAS1, GOLGA6L1 and WNT16 were found to be the second group of frequently mutated genes which found in to occur at a frequency of 60% in resistant patients. After cosine similarity analysis with 30 known signatures, three mutational signatures (signature a, b and c) were found in all CRC tumors, similar to Signature 1, 5 and 6 in COSMIC, respectively. Gene ontology analysis was performed on SMGs and found twelve enriched GO terms. Four genes are enriched in six specific KEGG pathway groups, such as metabolism of xenobiotics by cytochrome P450, Steroid hormone biosynthesis, retinol metabolism and drug metabolism. In conclusion, we show that the establishment of a WES clinical study of Cetuximab resistance CRC with prospective follow-up of patients can help to identify candidate predictive biomarkers of response.
Note: This abstract was not presented at the meeting.
Citation Format: Changwen Jing, Ting Wang, Rong Ma, Haixia Cao, EnShun Xu, Zhuo Wang, Siwen Liu, Dan Chen, Junying Zhang, Yang Wu, Yuan Zhang, Ping Ding, Michael Y. Sha, Jianzhong Wu, Jifeng Feng. New genetic variations discovered in KRAS wild-type cetuximab resistant Chinese colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1703.
Abstract 1708: An integrated framework for genome analysis reveals numerous previously unrecognizable structural variants in leukemia patients’ samples
Authors: Broach James R. , Xu Jie , Schleicher Emily , Pool Christopher , Hennessy Max , Sheldon Kathryn , Annageldiyev Charyguly , Sharma Arati , Chang Yuanyuan , Hastie Alex , Miller Barbara , Goldenberg David , Claxton David , Moldovan George-Lucian , Yue Feng 
Published: August 2019

Abstract
We have applied a combination of whole genome sequencing and optical genomic mapping to a number of adult and pediatric leukemia samples, which revealed in each of these samples a large number of structural variants not recognizable by current standard genomic analyses. We developed computational methods to determine which of those variants likely arose as somatic mutations. The method identified 97% of the translocations previously reported by karyotype analysis of these samples and revealed an additional fivefold more such somatic rearrangements. The method identified on average tens of previously unrecognizable inversions and duplications and hundreds of previously unrecognizable insertions and deletions. These structural variants affected a number of leukemia associated genes as well as cancer driver genes not previously associated with leukemia and genes not previously associated with cancer. A number of variants only affected intergenic regions but caused cis-acting alterations in expression of neighboring genes. Analysis of TCGA data indicates that several of the recurrently mutated genes significantly affect survival of AML patients. Our results suggest that current genomic analysis methods fail to identify a majority of structural variants in leukemia samples and this lacunae may hamper diagnostic and prognostic efforts.
Note: This abstract was not presented at the meeting.
Citation Format: James R. Broach, Jie Xu, Emily Schleicher, Christopher Pool, Max Hennessy, Kathryn Sheldon, Charyguly Annageldiyev, Arati Sharma, Yuanyuan Chang, Alex Hastie, Barbara Miller, David Goldenberg, David Claxton, George-Lucian Moldovan, Feng Yue. An integrated framework for genome analysis reveals numerous previously unrecognizable structural variants in leukemia patients’ samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1708.
Abstract 1713: Molecular dissection of Zc3h8 functional domains and the implications for the oncogenic phenotype
Authors: Schmidt John A. , Doan Tyler , Irizarry Emanuel , Harris Emily , Danielson Keith G. , Knepper Janice E. 
Published: August 2019

Abstract
Zc3h8 encodes a zinc finger protein that is amplified in 2-6% of human breast tumors. Higher expression of Zc3h8 also results in lower rates of disease-free survival. Amplification of Zc3h8 expression has been shown to increase cell proliferation, migration, invasion and tumor growth in mice. Conversely, decreased expression alters cell behavior by decreasing cell proliferation, migration, invasion, and tumor growth in mice. Zc3h8 comprises three CCCH non-classical zinc finger domains at the C-terminus of the protein that we hypothesize bind to RNA. The interactions between Zc3h8 and nucleic acids may be important for the localization and/or function of Zc3h8 and therefore may be important for the cellular phenotypes observed when the gene is over or under expressed in cells. We used in vitro and in vivo assays to demonstrate that mutations in any of the three zinc finger domains results in a protein that fails to rescue aggressive cellular phenotypes in cells with reduced expression of Zc3h8, while the wild type protein can rescue these phenotypes. This implies that all three zinc finger domains are required for Zc3h8 function in promoting rapid and aggressive cell proliferation. In addition to zinc finger domains, Zc3h8 also contains a casein kinase-2 (CK2) phosphorylation site that may be important for protein localization and/or activation. We have previously shown that CK2 inhibitors alter Zc3h8 localization to nuclear PML Bodies. Mouse cells overexpressing Zc3h8 with a Thr to Ala (T32A) change that prevents CK2 phosphorylation grow very slowly in culture and cannot grow in more challenging 3D or soft agar growth chambers. However, Zc3h8 with a Thr to Glu (T32E) change that mimics constitutive CK2 phosphorylation results in rapidly growing cells that surpass overexpression of Zc3h8 wild type. Zc3h8 phospho-mutants also have altered localization with Zc3h8 T32E becoming diffuse in the nucleus and T32A localizing to nuclear foci. These data suggest that the phosphorylation state of Zc3h8 and its ability to bind nucleic acids via zinc finger domains are critical for the oncogenic behavior that results from amplified expression. We also hypothesize that Zc3h8 has an important role in establishing or maintaining PML Bodies involved in genome maintenance, transcription, and/or post-transcription regulation.
Citation Format: John A. Schmidt, Tyler Doan, Emanuel Irizarry, Emily Harris, Keith G. Danielson, Janice E. Knepper. Molecular dissection of Zc3h8 functional domains and the implications for the oncogenic phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1713.
Abstract 1715: Sox2 is required for tumor initiation and maintenance in small cell lung cancer
Authors: Voigt Ellen , Thompson Ethan , Wollenzien Hannah , Kamp Madeline Vande , Kareta Michael S. 
Published: August 2019

Abstract
Some cancer prognoses have been radically improved in recent years, but little headway has been made with others. One of these diseases, small cell lung cancer (SCLC,) has a five-year survival rate of less than 7% and a standard of care that has been essentially unchanged for forty years. One promising avenue to improve SCLC outcomes is to understand the cancer’s underlying genetic alterations that drive its formation and growth. One primary driver of SCLC, is the loss of Rb gene function, one of the most common occurrences in human cancers. Normally Rb promotes differentiation by regulating lineage specific transcription factors concurrent with repression of the pluripotency factors such as Sox2. However, there is evidence that when certain tissues lose Rb, Sox2 becomes upregulated and promotes oncogenesis. To understand the contribution of Sox2 to SCLC, we have utilized a genetically engineered mouse model for SCLC to determine the consequence of Sox2 on SCLC tumor initiation and growth. We observe that Sox2 is indeed required for SCLC. Further elucidation of the Sox2 network in SCLC could identify candidates for future targeted therapies in this devastating disease.
Citation Format: Ellen Voigt, Ethan Thompson, Hannah Wollenzien, Madeline Vande Kamp, Michael S. Kareta. Sox2 is required for tumor initiation and maintenance in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1715.