Article
Biology
Shinichi Namba, Toshihide Ueno, Shinya Kojima, Kenya Kobayashi, Katsushige Kawase, Yosuke Tanaka, Satoshi Inoue, Fumishi Kishigami, Shusuke Kawashima, Noriko Maeda, Tomoko Ogawa, Shoichi Hazama, Yosuke Togashi, Mizuo Ando, Yuichi Shiraishi, Hiroyuki Mano, Masahito Kawazu
Summary: The MuSTA pipeline enables efficient transcriptome assembly from long-read sequencing data of breast cancer samples, leading to the discovery of subtype-specific isoforms and genomic context-dependent fusion transcript structures. This method sheds light on the influence of chromosomal structural alterations on cancer transcriptomes.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Aaron N. Brooks, Amanda L. Hughes, Sandra Clauder-Muenster, Leslie A. Mitchell, Jef D. Boeke, Lars M. Steinmetz
Summary: This study investigates the effects of sequence features and transcriptional context on RNA transcript isoform expression. Using synthetic yeast strains with rearranged genes, the researchers discovered that neighboring transcription also influences gene expression levels and transcript isoform boundaries. They identified features of transcriptional context that can predict these alterations and successfully engineered a synthetic circuit where transcript length is controlled by neighboring transcription.
Article
Pathology
Araceli Garcia-Martinez, Ariadna Perez-Balaguer, Fernando Ortiz-Martinez, Eloy Pomares-Navarro, Elena Sanmartin, Marta Garcia-Escolano, Yoel G. Montoyo-Pujol, Elena Castellon-Molla, Gloria Peiro
Summary: The study revealed differential activation of the Hh pathway in breast carcinoma phenotypes. SMO levels stratify patients at risk of recurrence and death in the HER2 phenotype, showing independent prognostic value and potential therapeutic significance.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Cell Biology
Marcel Werner, Anna Dyas, Iwan Parfentev, Geske E. Schmidt, Iga K. Mieczkowska, Lukas C. Mueller-Kirschbaum, Claudia Mueller, Stefan Kalkhof, Oliver Reinhardt, Henning Urlaub, Frauke Alves, Julia Gallwas, Evangelos Prokakis, Florian Wegwitz
Summary: This study reveals the molecular mechanisms underlying the acquisition of aggressive and chemotherapy-resistant phenotypes in basal-like breast cancer (BLBC) cells. The short isoform of Roundabout Guidance Receptor 3 (ROBO3s) was found to play an important role in mediating cancer stem cell properties and driving resistance of BLBC cells to cytotoxic drugs. The expression of ROBO3s is conserved across multiple cancer types and is associated with reduced survival in BLBC patients, highlighting its potential as a prognostic marker and a novel target for anti-cancer drug development.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Joel S. Parker, Michael Mullins, Maggie C. U. Cheang, Samuel Leung, David Voduc, Tammi Vickery, Sherri Davies, Christiane Fauron, Xiaping He, Zhiyuan Hu, John F. Quackenbush, Inge J. Stijleman, Juan Palazzo, J. S. Marron, Andrew B. Nobel, Elaine Mardis, Torsten O. Nielsen, Matthew J. Ellis, Charles M. Perou, Philip S. Bernard
Summary: This study developed a risk model that incorporates gene expression-based intrinsic subtypes for breast cancer prognosis and prediction of chemotherapy benefit. The intrinsic subtypes showed significant prognostic significance and remained significant even when standard parameters were incorporated. The model can be used to predict prognosis for node-negative breast cancer and assess the likelihood of efficacy from neoadjuvant chemotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Mai Ahmed Shafei, Arwa Flemban, Carl Daly, Paul Kendrick, Paul White, Sarah Dean, David Qualtrough, Myra E. Conway
Summary: Biological characterisation of breast cancer subtypes reveals a differential metabolic reliance, with cytosolic isoform of BCAT associated with HER2 + and luminal B subtypes while the mitochondrial isoform is highly expressed in ER + tumours, indicating potential novel therapeutic targets for dysregulated cancer metabolism.
Article
Multidisciplinary Sciences
Manuela Gago-Dominguez, Carmen M. Redondo, Manuel Calaza, Marcos Matabuena, Maria A. Bermudez, Roman Perez-Fernandez, Maria Torres-Espanol, Angel Carracedo, J. Esteban Castelao
Summary: The study revealed an association between LIPG and breast cancer, particularly in specific conditions including pre-menopausal breast cancer, Luminal A breast cancers, HER2-negative breast cancers, women with high total cholesterol levels, non-postpartum breast cancer, and grades II and III breast cancers.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Qianying Guo, Hao Wang, Jiahao Duan, Wenwu Luo, Rongrong Zhao, Yuting Shen, Bijun Wang, Siqi Tao, Yi Sun, Qian Ye, Xiaomin Bi, Hui Yuan, Qiang Wu, Peter E. Lobie, Tao Zhu, Sheng Tan, Xing Huang, Zhengsheng Wu
Summary: A novel p62 mRNA isoform that escapes miRNA-mediated repression and leads to increased p62 protein expression was found to be associated with chemoresistance in breast cancer cells and tissue specimens.
Article
Multidisciplinary Sciences
Diogo F. T. Veiga, Alex Nesta, Yuqi Zhao, Anne Deslattes Mays, Richie Huynh, Robert Rossi, Te-Chia Wu, Karolina Palucka, Olga Anczukow, Christine R. Beck, Jacques Banchereau
Summary: This study developed a LR RNA sequencing and analytical platform to identify and annotate full-length transcripts and tumor-specific splicing events in cancer. The results revealed the presence of previously unannotated transcripts in breast cancer, some of which affected protein coding regions and were predicted to alter protein localization and function. Additionally, tumor-specific splicing events significantly associated with patient survival were identified, providing a rich resource of immuno-oncology therapeutic targets.
Review
Neurosciences
Joun Park, Shannon Farris
Summary: Proper development and plasticity of hippocampal neurons require specific RNA isoforms to be expressed in the right place at the right time. This review describes the RNA processing strategies utilized by hippocampal neurons to regulate the spatiotemporal expression of critical genes. The hippocampus serves as an ideal investigative model for uncovering isoform-specific mechanisms that restrict transcript expression in space and time.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Zhihong Gong, Jianhong Chen, Jie Wang, Song Liu, Christine B. Ambrosone, Michael J. Higgins
Summary: The study found that DNA methylation changes within miRNA genes are associated with altered miRNA expression in breast cancer among both African American and European American women, potentially contributing to subtype- and race-related tumor biological differences.
Article
Biochemical Research Methods
Shuhui Liu, Yupei Zhang, Xuequn Shang
Summary: Breast cancer is a heterogeneous disease caused by various alterations in the genome or transcriptome, and identifying useful biomarkers is crucial for understanding the underlying biological mechanisms and guiding clinical decisions. In this study, we propose GLassonet, a feature selection method that uses a neural network and graph enhancement to identify discriminative biomarkers from transcriptome-wide expression profiles. Experimental results show that GLassonet effectively selects discriminative genes and improves cancer subtype classification performance, providing potential biomarkers for personalized therapy.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Amy Tresenrider, Kaitlin Morse, Victoria Jorgensen, Minghao Chia, Hanna Liao, Folkert Jacobus van Werven, Elcin Unal
Summary: The study found that long undecoded transcript isoforms (LUTIs) downregulate gene expression through transcriptional and translational repression, with varying effects on transcriptional repression and ubiquitous presence of translational repression. Predictive factors for LUTI-based transcriptional repression include LUTI expression levels, enrichment of histone 3 lysine 36 trimethylation, and changes in nucleosome position.
Article
Biochemical Research Methods
Alma Andersson, Joakim Lundeberg
Summary: In this study, a novel method was proposed to analyze spatial transcriptomics data, which simulated the diffusion of individual transcripts to extract genes with spatial patterns, generating satisfactory results on synthetic and real data. Compared to existing methods, this approach seemed to be less influenced by gene expression levels and showed better time performance when run with multiple cores.
Article
Multidisciplinary Sciences
Yan Zhu, Wenjie Sun, Xueping Jiang, Rui Bai, Yuan Luo, Yanping Gao, Shuying Li, Zhengrong Huang, Yan Gong, Conghua Xie
Summary: Different transcript variants of WRAP53 gene have different functions in non-small cell lung cancer cells and regulate cell behaviors depending on the expression level of p53.
Correction
Biotechnology & Applied Microbiology
Sergei Yakneen, Sebastian M. Waszak, Michael Gertz, Jan O. Korbel, Brice Aminou, Javier Bartolome, Keith A. Boroevich, Rich Boyce, Angela N. Brooks, Alex Buchanan, Ivo Buchhalter, Adam P. Butler, Niall J. Byrne, Andy Cafferkey, Peter J. Campbell, Zhaohong Chen, Sunghoon Cho, Wan Choi, Peter Clapham, Brandi N. Davis-Dusenbery, Francisco M. De La Vega, Jonas Demeulemeester, Michelle T. Dow, Lewis Jonathan Dursi, Juergen Eils, Roland Eils, Kyle Ellrott, Claudiu Farcas, Francesco Favero, Nodirjon Fayzullaev, Vincent Ferretti, Paul Flicek, Nuno A. Fonseca, Josep Ll. Gelpi, Gad Getz, Bob Gibson, Robert L. Grossman, Olivier Harismendy, Allison P. Heath, Michael C. Heinold, Julian M. Hess, Oliver Hofmann, Jongwhi H. Hong, Thomas J. Hudson, Barbara Hutter, Carolyn M. Hutter, Daniel Hubschmann, Seiya Imoto, Sinisa Ivkovic, Seung-Hyup Jeon, Wei Jiao, Jongsun Jung, Rolf Kabbe, Andre Kahles, Jules N. A. Kerssemakers, Hyung-Lae Kim, Hyunghwan Kim, Jihoon Kim, Youngwook Kim, Kortine Kleinheinz, Michael Koscher, Antonios Koures, Milena Kovacevic, Chris Lawerenz, Ignaty Leshchiner, Jia Liu, Dimitri Livitz, George L. Mihaiescu, Sanja Mijalkovic, Ana Mijalkovic Lazic, Satoru Miyano, Naoki Miyoshi, Hardeep K. Nahal-Bose, Hidewaki Nakagawa, Mia Nastic, Steven J. Newhouse, Jonathan Nicholson, Brian D. O'Connor, David Ocana, Kazuhiro Ohi, Lucila Ohno-Machado, Larsson Omberg, B. F. Francis Ouellette, Nagarajan Paramasivam, Marc D. Perry, Todd D. Pihl, Manuel Prinz, Montserrat Puiggros, Petar Radovic, Keiran M. Raine, Esther Rheinbay, Mara Rosenberg, Romina Royo, Gunnar Ratsch, Gordon Saksena, Matthias Schlesner, Solomon I. Shorser, Charles Short, Heidi J. Sofia, Jonathan Spring, Lincoln D. Stein, Adam J. Struck, Grace Tiao, Nebojsa Tijanic, David Torrents, Peter Van Loo, Miguel Vazquez, David Vicente, Jeremiah A. Wala, Zhining Wang, Sebastian M. Waszak, Joachim Weischenfeldt, Johannes Werner, Ashley Williams, Youngchoon Woo, Adam J. Wright, Qian Xiang, Liming Yang, Denis Yuen, Christina K. Yung, Junjun Zhang, Jan O. Korbel
NATURE BIOTECHNOLOGY
(2023)
Article
Medicine, Research & Experimental
Christina A. Clarke, Kathryn Lang, Girish Putcha, Jonathan P. Beer, Maude Champagne, Andrea Ferris, James H. Godsey, Robert L. Grossman, Jody M. Hoyos, Donald J. Johann, Nancy Krunic, Peter Kuhn, Jerry S. H. Lee, Tara Maddala, Marielena Mata, Jeremiah McDole, Omar Perez, Howard Scher, Mark D. Stewart, Seema Singh Bhan, Qu Zhang, Lauren C. Leiman
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Hematology
Andrew J. Shih, Tomi Jun, Andrew D. Skol, Riyue Bao, Lei Huang, Sapana Vora, Megan E. McNerney, Eric A. Hungate, Michelle M. Le Beau, Richard A. Larson, Aaron Elliott, Hsiao-Mei Lu, Robert Huether, Felicia Hernandez, Friedrich Stolzel, James M. Allan, Kenan Onel
Summary: Some patients with therapy-related myeloid neoplasms (t-MN) may have unsuspected inherited cancer predisposition syndrome (CPS). A set of clinical criteria has been proposed to identify t-MN patients with high risk of CPS (HR-CPS). Among the identified HR-CPS patients, 37% had pathogenic or likely pathogenic variants, compared to 0% in the low-risk CPS patients. These simple clinical criteria help identify t-MN patients most likely to benefit from genetic testing for inherited CPS.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Shan Wang, Xiaofang Huo, Yiping Yang, Yingxi Mo, Rahul K. Kollipara, Ralf Kittler
Summary: The deubiquitinase USP9X stabilizes EWS-FLI1 protein expression in Ewing sarcoma, and its inhibitor WP1130 can rapidly degrade EWS-FLI1 and inhibit the growth of Ewing sarcoma cells and tumors.
Review
Oncology
Shawn M. Sweeney, Hisham K. Hamadeh, Natalie Abrams, Stacey J. Adam, Sara Brenner, Dana E. Connors, Gerard J. Davis, Louis D. Fiore, Susan H. Gawel, Robert L. Grossman, Sean E. Hanlon, Karl Hsu, Gary J. Kelloff, Ilan R. Kirsch, Bill Louv, Deven McGraw, Frank Meng, Daniel Milgram, Robert S. Miller, Emily Morgan, Lata Mukundam, Thoma O'Brien, Paul Robbins, Eric H. Rubin, Wendy S. Rubinstein, Liz Salmi, Teilo H. Schaller, George Shi, Caroline C. Sigman, Sudhir Srivastava
Summary: The analysis of big healthcare data has great potential in advancing oncology drug development and patient treatment in precision medicine. However, challenges exist in organizing, sharing, integrating, and making data accessible. This review presents five case studies showcasing successful approaches to addressing these challenges and emphasizes the need for data sharing and utilization to advance cancer research and treatment.
Review
Oncology
Shawn M. Sweeney, Hisham K. Hamadeh, Natalie Abrams, Stacey J. Adam, Sara Brenner, Dana E. Connors, Gerard J. Davis, Louis Fiore, Susan H. Gawel, Robert L. Grossman, Sean E. Hanlon, Karl Hsu, Gary J. Kelloff, Ilan R. Kirsch, Bill Louv, Deven McGraw, Frank Meng, Daniel Milgram, Robert S. Miller, Emily Morgan, Lata Mukundan, Thomas O'Brien, Paul Robbins, Eric H. Rubin, Wendy S. Rubinstein, Liz Salmi, Teilo Schaller, George Shi, Caroline C. Sigman, Sudhir Srivastava
Summary: Big data in healthcare, including electronic health records, medical imaging, genomic sequencing, payor records, and data from pharmaceutical research, wearables, and medical devices, can provide unprecedented understanding of diseases and their treatment. However, challenges such as interoperability, data quality, and data privacy need to be addressed to fully leverage the potential of big data in medicine. Organizations sharing data in a precompetitive manner, establishing agreements on data quality standards, and implementing universal and practical data privacy principles are key to realizing the benefits of big data in healthcare.
Article
Biochemistry & Molecular Biology
Ningfei An, Saira Khan, Molly K. K. Imgruet, Lia Jueng, Sandeep Gurbuxani, Megan E. E. McNerney
Summary: -7/del(7q) is commonly found in myeloid neoplasms. CUX1, located on 7q22, is a transcription factor associated with poor prognosis when mutated. CUX1 deficiency and oncogenic RAS mutations are found to be linked and promote leukemogenesis. This research indicates a potential therapy for malignancies with CUX1 inactivation.
Article
Oncology
Anne -Florence Blandin, Ross Giglio, Maya Srikanth Graham, Guadalupe Garcia, Seth Malinowski, Jared K. Woods, Shakti Ramkissoon, Lori Ramkissoon, Frank Dubois, Kathleen Schoolcraft, Jessica Tsai, Dayle Wang, Robert Jones, Jayne Vogelzang, Kristine Pelton, Sarah Becker, Fiona Watkinson, Claire Sinai, Elizabeth F. Cohen, Matthew A. Booker, Michael Y. Tolstorukov, Veerle Haemels, Liliana Goumnerova, Karen Wright, Mark Kieran, Katie Fehnel, David Reardon, Arnault Tauziede-Espariat, Rishi Lulla, Benjamin Carcamo, Stanley Chaleff, Alain Charest, Frederik De Smet, Azra H. Ligon, Adrian Dubuc, Melanie Pages, Pascale Varlet, Patrick Y. Wen, Brian M. Alexander, Susan Chi, Sanda Alexandrescu, Ralf Kittler, Robert Bachoo, Pratiti Bandopadhayay, Rameen Beroukhim, Keith L. Ligon
Summary: This study comprehensively analyzed ALK expression and genomic aberrations in 371 glioblastomas and validated the abnormalities in vitro and in vivo. The findings showed that ALK aberrations were present in 12% of gliomas across a wide age range and ALK fusions were more common in congenital/infant glioblastomas. ALK fusions promoted pathways related to tumor transformation and responded well to ALK inhibitors, supporting their use in clinical trials for glioblastomas in different age groups.
CLINICAL CANCER RESEARCH
(2023)
Article
Computer Science, Information Systems
Stan Ahalt, Paul Avillach, Rebecca Boyles, Kira Bradford, Steven Cox, Brandi Davis-Dusenbery, Robert L. Grossman, Ashok Krishnamurthy, Alisa Manning, Benedict Paten, Anthony Philippakis, Ingrid Borecki, Shu Hui Chen, Jon Kaltman, Sweta Ladwa, Chip Schwartz, Alastair Thomson, Sarah Davis, Alison Leaf, Jessica Lyons, Elizabeth Sheets, Joshua C. Bis, Matthew Conomos, Alessandro Culotti, Thomas Desain, Jack Digiovanna, Milan Domazet, Stephanie Gogarten, Alba Gutierrez-Sacristan, Tim Harris, Ben Heavner, Deepti Jain, Brian O'Connor, Kevin Osborn, Danielle Pillion, Jacob Pleiness, Ken Rice, Garrett Rupp, Arnaud Serret-Larmande, Albert Smith, Jason P. Stedman, Adrienne Stilp, Teresa Barsanti, John Cheadle, Christopher Erdmann, Brandy Farlow, Allie Gartland-Gray, Julie Hayes, Hannah Hiles, Paul Kerr, Chris Lenhardt, Tom Madden, Joanna O. Mieczkowska, Amanda Miller, Patrick Patton, Marcie Rathbun, Stephanie Suber, Joe Asare
Summary: The NHLBI BioData Catalyst (BDC) is a community-driven ecosystem developed by the National Heart, Lung, and Blood Institute. It provides researchers with access to large-scale datasets and computational resources for precision medicine research. The BDC offers secure, cloud-based workspaces, authentication and authorization systems, search functionalities, tools and workflows, and innovative features to meet the needs of the research community. It has also played a significant role in accelerating research on the COVID-19 pandemic.
JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
(2023)
Article
Biochemical Research Methods
Michael Lukowski, Andrew Prokhorenkov, Robert L. Grossman
Summary: We introduce a self-describing serialized format called Portable Format for Biomedical (PFB) data for bulk biomedical data. PFB is based on Avro and includes a data model, a data dictionary, the data itself, and pointers to third party controlled vocabularies. Each data element in the data dictionary is associated with a third party controlled vocabulary for easier harmonization of PFB files. We also introduce an open source SDK called PyPFB for creating, exploring and modifying PFB files. Experimental studies show improved performance of importing and exporting bulk biomedical data in the PFB format compared to JSON and SQL formats.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Editorial Material
Multidisciplinary Sciences
Robert L. Grossman
Summary: A data commons is a cloud-based data platform that allows a community to manage, analyze, and share data. It enables research communities to utilize cloud computing for large-scale data management and analysis, and securely share data, thereby accelerating research progress.
Article
Medicine, Research & Experimental
Samadrita Bhattacharyya, Rahul K. Kollipara, Gabriela Orquera-Tornakian, Sean Goetsch, Minzhe Zhang, Cameron Perry, Boxun Li, John M. Shelton, Minoti Bhakta, Jialei Duan, Yang Xie, Guanghua Xiao, Bret M. Evers, Gary C. Hon, Ralf Kittler, Nikhil V. Munshi
Summary: A comprehensive CCS-enriched CRE database named CCS-ATAC was established for studying CCS-wide and component-specific regulatory functions. CCS component-specific gene regulatory networks (GRNs) were constructed using transcription factor (TF) motifs, and specific TF sub-networks were identified and confirmed. CCS-ATAC was leveraged to improve annotation of existing human variants related to cardiac rhythm, and a potential dysregulated enhancer-target pair by a specific SNP was nominated.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Meeting Abstract
Oncology
Mia Hofstad, Lan Yu, Andrea Woods, Zoi Sychev, Collin Gilbreath, Xiaofang Huo, Ralf Kittler, Justin M. Drake, Ganesh V. Raj
Meeting Abstract
Oncology
Anne-Florence Blandin, Ross Giglio, Maya Srikanth Graham, Guadalupe Garcia, Seth Malinowski, Jared K. Woods, Shakti Ramkissoon, Lori Ramkissoon, Frank Dubois, Kate Schoolcraft, Jessica W. Tsai, Dayle K. Wang, Robert Jones, Jayne Vogelzang, Kristine Pelton, Sarah Becker, Fiona Watkinson, Claire Sinai, Elizabeth Cohen, Matthew Booker, Michael Tolstorukov, Veerle Haemels, Liliana Goumnerova, Karen Wright, Mark Kieran, Katie Fehnel, David Reardon, Arnault Tauziede-Espariat, Rishi Lulla, Benjamin Carcamo, Stanley Chaleff, Alain Charest, Frederik De Smet, Azra H. Ligon, Adrian Dubuc, Melanie Pages, Pascale Varlet, Patrick Wen, Brian Alexander, Susan Chi, Sanda Alexandrescu, Ralf Kittler, Robert Bachoo, Rameen Beroukhim, Pratiti Bandopadhayay, Keith L. Ligon
Article
Oncology
Kenneth E. Huffman, Long Shan Li, Ryan Carstens, Hyunsil Park, Luc Girard, Kimberley Avila, Shuguang Wei, Rahul Kollipara, Brenda Timmons, Jessica Sudderth, Nawal Bendris, Jiyeon Kim, Pamela Villalobos, Junya Fujimoto, Sandra Schmid, Ralph J. Deberardinis, Ignacio Wistuba, John Heymach, Ralf Kittler, Esra A. Akbay, Bruce Posner, Yuzhuo Wang, Stephen Lam, Steven A. Kliewer, David J. Mangelsdorf, John D. Minna
Summary: Glucocorticoid receptor (GR) is an important target for anti-cancer therapies in lymphoid cancers. This study finds that a dexamethasone-GR mediated anti-cancer response exists in a subset of aggressive non-small cell lung cancers (NSCLCs) with STK11/LKB1 mutations. The high expression of carbamoyl phosphate synthase 1 (CPS1) is strongly linked to LKB1 mutations and serves as a predictor of NSCLC dexamethasone sensitivity.
FRONTIERS IN ONCOLOGY
(2023)