Article
Biochemical Research Methods
Luca Barbon, Victoria Offord, Elizabeth J. Radford, Adam P. Butler, Sebastian S. Gerety, David J. Adams, Hong Kee Tan, Andrew J. Waters
Summary: This article introduces a variant library annotation tool called VaLiAnT, which can generate variant libraries based on user-defined genomic coordinates and standard input files. The software is applicable to diverse fields and is configurable.
Article
Immunology
Arutha Kulasinghe, Ning Liu, Chin Wee Tan, James Monkman, Jane E. Sinclair, Dharmesh D. Bhuva, David Godbolt, Liuliu Pan, Andy Nam, Habib Sadeghirad, Kei Sato, Gianluigi Li Bassi, Ken O'Byrne, Camila Hartmann, Anna Flavia Ribeiro Dos Santos Miggiolaro, Gustavo Lenci Marques, Lidia Zytynski Moura, Derek Richard, Mark Adams, Lucia de Noronha, Cristina Pellegrino Baena, Jacky Y. Suen, Rakesh Arora, Gabrielle T. Belz, Kirsty R. Short, Melissa J. Davis, Fernando Souza-Fonseca Guimaraes, John F. Fraser
Summary: The study reveals distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection, with upregulation of genes associated with DNA damage and repair, heat shock, and macrophage infiltration in COVID-19 patients' cardiac tissues. In comparison, pH1N1 infection showed upregulation of interferon and complement pathways. This highlights the need for further understanding of the effects on extra-pulmonary organs, including the cardiovascular system, in COVID-19 patients.
Article
Genetics & Heredity
Eleanor Wong, Nicolas Bertin, Maxime Hebrard, Roberto Tirado-Magallanes, Claire Bellis, Weng Khong Lim, Chee Yong Chua, Philomena Mei Lin Tong, Raymond Chua, Kenneth Mak, Tit Meng Lim, Wei Yang Cheong, Kwee Eng Thien, Khean Teik Goh, Jin-Fang Chai, Jimmy Lee, Joseph Jao-Yiu Sung, Tien Yin Wong, Calvin Woon Loong D. Chin, Peter Gluckman, Liuh Ling Goh, Kenneth Hon Kim Ban, Tin Wee M. Tan, Rob M. Van Dam, Yik Ying Teo, Marie Loh, Paul Eillot, Eng Sing Lee, Joanne Ngeow, Elio Riboli, Rinkoo Dalan, Irfahan Kassam, Lakshmi Narayanan Lakshmanan, Tock Han Lim, Hong Kiat Ng, Theresia Mina, Darwin Tay, Charumathi Sabanayagam, Yih Chung Tham, Tyler Rim, Tin Aung, Miao Ling Chee, Hengtong Li, Miao Li Chee, Khung Keong Yeo, Stuart Alexander Cook, Chee Jian Pua, Chengxi Yang, Yap Seng Chong, Johan Gunnar Eriksson, Kok Hian Tan, Fabian Yap, Chia Wei Lim, Pi Kuang Tsai, Wen Jie Chew, Wey Ching Sim, Li-xian Grace Toh, Clarabelle Bitong Lin, Yee Yen Sia, Tat Hung Koh, Wee Yang Meah, Joanna Hui Juan Tan, Justin Jeyakani, Jack Ow, Shimin Ang, Ashar J. Malik, Dimitar Kenanov, Xueling Sim, Ching-Yu Cheng, Sonia Davila, Neerja Karnani, Khai Pang Leong, Jianjun Liu, Shyam Prabhakar, Sebastian Maurer-Stroh, Chandra Shekhar Verma, Pavitra Krishnaswamy, Rick Siow Mong Goh, Irenaeus Chia, Clarissa Ho, Doreen Low, Suchin Virabhak, Jacklyn Yong, Weiling Zheng, Shih Wee Seow, Yee Kwang Seck, Mingshi Koh, John C. Chambers, E. Shyong Tai, Patrick Tan
Summary: This article discusses Singapore's efforts to establish a National Precision Medicine Strategy by integrating genomic, clinical, and lifestyle data of up to one million individuals. Precision medicine has the potential to revolutionize healthcare by detecting diseases early, refining diagnoses, and tailoring treatments for groups and individuals. The lack of representation of Asian ancestries in existing genomic-phenotypic databases presents a missed opportunity for new discoveries, especially for diseases relevant to these populations. The Singapore National Precision Medicine initiative aims to generate integrated data from various sources over a 10-year period, including genomic, lifestyle, health, social, and environmental data, in order to promote precision medicine adoption and address social, ethical, legal, and regulatory challenges.
Review
Oncology
Elysse K. Morris, Sheena Daignault-Mill, Samantha J. Stehbens, Laura A. Genovesi, Anne K. Lagendijk
Summary: Brain tumors are a major cause of death and illness in children, but current treatments are not effective enough. The blood-brain-barrier (BBB) limits the penetration of anticancer drugs into the brain. Tumors can compromise the BBB, known as the blood-brain-tumor-barrier (BBTB), affecting the effectiveness of therapy. However, the heterogeneity of barrier alteration within a tumor and across different pediatric tumor types poses a challenge.
FRONTIERS IN ONCOLOGY
(2023)
Article
Medical Informatics
Albert Burger, Richard A. Baldock, David J. Adams, Shahida Din, Irene Papatheodorou, Michael Glinka, Bill Hill, Derek Houghton, Mehran Sharghi, Michael Wicks, Mark J. Arends
Summary: This study describes a conceptual coordinate model for the Gut Cell Atlas, which represents the location of the human gut in 1D, 2D, and 3D models. It allows clinicians and pathologists to accurately describe gut locations and perform cell comparison analysis.
BMC MEDICAL INFORMATICS AND DECISION MAKING
(2023)
Article
Genetics & Heredity
Tuan Vo, Brad Balderson, Kahli Jones, Guiyan Ni, Joanna Crawford, Amanda Millar, Elissa Tolson, Matthew Singleton, Marija Kojic, Thomas Robertson, Shaun Walters, Onkar Mulay, Dharmesh D. Bhuva, Melissa J. Davis, Brandon J. Wainwright, Quan Nguyen, Laura A. Genovesi
Summary: This study used spatially resolved transcriptomics to investigate the cellular diversity and spatial organization of medulloblastoma (MB) and its impact on therapy response. By integrating spatial gene expression, histological annotation, and single-cell gene expression data, the study identified specific cellular states and spatial locations that are crucial for the response to CDK4/6 inhibitor Palbociclib. The study also revealed a distinct tumor interface with neighboring brain tissue, where the tumor continued to proliferate despite Palbociclib treatment.
Article
Cell Biology
Guia Cerretelli, Ying Zhou, Mike F. Muller, David J. Adams, Mark J. Arends
Summary: This study found that defective MMR interacts with acetaldehyde, enhancing colonic tumor formation. Loss of ALDH1B1 increases acetaldehyde levels and DNA damage that interacts with dMMR to accelerate colonic tumor formation.
DISEASE MODELS & MECHANISMS
(2023)
Article
Pathology
Christine L. White, Kathryn M. Kinross, Molly K. Moore, Elnaz Rasouli, Robyn Strong, Janelle M. Jones, Jason E. Cain, Dominik Sturm, Felix Sahm, David T. W. Jones, Stefan M. Pfister, Thomas Robertson, Colleen D'Arcy, Michael L. Rodriguez, Jason M. Dyke, Reimar Junckerstorff, Dharmesh D. Bhuva, Melissa J. Davis, Paul Wood, Tim Hassall, David S. Ziegler, Stewart Kellie, Geoffrey McCowage, Frank Alvaro, Maria Kirby, John A. Heath, Karen Tsui, Andrew Dodgshun, David D. Eisenstat, Dong-Anh Khuong-Quang, Meaghan Wall, Elizabeth M. Algar, Nicholas G. Gottardo, Jordan R. Hansford
Summary: DNA methylation array profiling is a valuable tool for classifying and diagnosing pediatric central nervous system tumors. This study conducted a prospective diagnostic trial involving multiple pediatric cancer centers and validated the results with a parallel study. The findings demonstrate the feasibility and accuracy of this technique in clinical practice for predicting tumor classification. The high accuracy and reliability of the DNA methylation array profiling provide valuable information for the diagnosis of CNS tumors.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2023)
Article
Biochemistry & Molecular Biology
Stephen J. Pettitt, Nan Shao, Diana Zatreanu, Jessica Frankum, Ilirjana Bajrami, Rachel Brough, Dragomir B. Krastev, Theodoros I. Roumeliotis, Jyoti S. Choudhary, Sonja Lorenz, Alistair Rust, Johann S. de Bono, Timothy A. Yap, Andrew N. J. Tutt, Christopher J. Lord
Summary: Reduced expression of HUWE1 leads to increased levels of BRCA1- increment 11q and PARPi resistance. This effect is specific to cells able to express BRCA1- increment 11q and is not seen in other BRCA1 or BRCA2 mutant cells. HUWE1 silencing also restores RAD51 nuclear foci and platinum salt resistance, indicating its potential as a biomarker for PARPi resistance in future clinical trials.
Article
Immunology
Rachel M. Koldej, Ashvind Prabahran, Chin Wee Tan, Mandy Ludford-Menting, Huw Morgan, Nicholas Holzwart, Melissa J. Davis, David S. Ritchie
Summary: This study reveals common mechanisms of immune dysregulation in poor graft function and acquired aplastic anemia, providing insights for therapeutic discovery and translation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Ayla Orang, B. Kate Dredge, Chi Yau Liu, Julie M. Bracken, Chun-Hsien Chen, Laura Sourdin, Holly J. Whitfield, Rachael Lumb, Sarah Boyle, Melissa J. Davis, Michael S. Samuel, Philip A. Gregory, Yeesim Khew-Goodall, Gregory J. Goodall, Katherine A. Pillman, Cameron P. Bracken
Summary: Epithelial-mesenchymal transition is regulated by basonuclin-2 (BNC2), which controls the expression of specific collagens, matrix metalloproteases, and other matrisomal components. BNC2 also modulates the motile and invasive properties of cancers, and its high expression is associated with increasing cancer grade and poor patient prognosis.
LIFE SCIENCE ALLIANCE
(2023)
Letter
Biotechnology & Applied Microbiology
Douglas M. Fowler, David J. Adams, Anna L. Gloyn, William C. Hahn, Debora S. Marks, Lara A. Muffley, James T. Neal, Frederick P. Roth, Alan F. Rubin, Lea M. Starita, Matthew E. Hurles, Nadav Ahituv, Orli G. Bahcal, Dustin Baldridge, Jonathan S. Berg, Alice H. Berger, Aisha Haley Bianchi, Benedetta Bolognesi, Michael Boutros, Steven Brenner, Matthew H. Brush, Vanessa Bryant, Carol J. Bult, Martha Bulyk, Melissa Call, Hannah Carter, Melina Claussnitzer, Feng Chen, Melissa S. Cline, Josh T. Cuperus, Moez Dawood, Hannah N. De Jong, Mafalda Dias, Michael Dunn, Jesse Engreitz, Kyle Farh, Phillip G. Febbo, Stanley Fields, Gregory M. Findlay, Helen Firth, James S. Fraser, Jonathan Frazer, Mattia Frontini, Irene Gallego Romero, Andrew M. Glazer, Murat Gueler, Rasmus Hartmann-Petersen, Richard Houlston, Kuan-Lin Huang, Carolyn M. Hutter, Sujatha Jagannathan, Richard G. James, Martin Kampmann, Rachel Karchin, Justin B. Kinney, Alexis C. Komor, Sriram Kosuri, Ben Lehner, Kresten Lindorff-Larsen, Zane Lombard, Daniel G. MacArthur, Maria Martin, Ultan McDermott, Shannon M. McNulty, Alex N. Nguyen Ba, Anne O'Donnell-Luria, Brian J. O'Roak, Victoria N. Parikh, Leopold Parts, Michael J. Pazin, Tina Pesaran, Slave Petrovski, Christine Queitsch, David E. Root, Jay Shendure, Amanda B. Spurdle, Kevin L. Taylor, Clare Turnbull, Judit Villen, L. E. L. M. Vissers, Alex H. Wagner, Matthew J. Wakefield, Jochen Weile, Jenny Xiao
Summary: Sequencing has identified numerous genetic variants in humans, but their functional effects remain largely unknown, hindering precision medicine. However, multiplexed variant effect assays can assess large numbers of variants simultaneously, generating variant effect maps that reveal the functional impact of every possible single nucleotide change. Creating an "Atlas" of variant effect maps for all protein encoding genes and regulatory elements in the human genome would revolutionize our understanding of genetics and enable advancements in therapeutics, human evolution, and disease diagnosis and treatment.
Article
Biochemical Research Methods
Dhananjay Kimothi, Pravesh Biyani, James M. Hogan, Melissa J. Davis
Summary: Protein-protein interactions play a crucial role in cell function. This paper explores the use of sequence embeddings to predict these interactions. The authors propose a method that constructs a feature vector by combining the embeddings of the constituent sequences. The results show that low dimensional sequence embeddings outperform alternative representations based on physico-chemical properties.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Shikhar Sharma, Chi-Yeh Chung, Sean Uryu, Jelena Petrovic, Joan Cao, Amanda Rickard, Nataliya Nady, Samantha Greasley, Eric Johnson, Oleg Brodsky, Showkhin Khan, Hui Wang, Zhenxiong Wang, Yong Zhang, Konstantinos Tsaparikos, Lei Chen, Anthony Mazurek, John Lapek, Pei-Pei Kung, Scott Sutton, Paul F. Richardson, Eric C. Greenwald, Shinji Yamazaki, Rhys Jones, Karen A. Maegley, Patrick Bingham, Hieu Lam, Alexandra E. Stupple, Aileen Kamal, Anderly Chueh, Anthony Cuzzupe, Benjamin J. Morrow, Bin Ren, Catalina Carrasco-Pozo, Chin Wee Tan, Dharmesh D. Bhuva, Elizabeth Allan, Elliot Surgenor, Francois Vaillant, Havva Pehlivanoglu, Hendrik Falk, James R. Whittle, Janet Newman, Joseph Cursons, Judy P. Doherty, Karen L. White, Laura Macpherson, Mark Devlin, Matthew L. Dennis, Meghan K. Hattarki, Melanie De Silva, Michelle A. Camerino, Miriam S. Butler, Olan Dolezal, Patricia Pilling, Richard Foitzik, Paul A. Stupple, H. Rachel Lagiakos, Scott R. Walker, Soroor Hediyeh-Zadeh, Stewart Nuttall, Sukhdeep Spall, Susan A. Charman, Theresa Connor, Thomas S. Peat, Vicky M. Avery, Ylva E. Bozikis, Yuqing Yang, Ming Zhang, Brendon J. Monahan, Anne K. Voss, Ian P. Street, Sarah-Jane Dawson, Mark A. Dawson, Geoffrey J. Lindeman, Melissa J. Davis, Jane E. Visvader, Thomas A. Paul
Summary: In this study, a highly potent, selective, and orally bioavailable KAT6A/KAT6B inhibitor CTx-648 was identified, which inhibits H3K23 acetylation and exhibits anti-tumor activity in ER+ breast cancer. The mechanism of action may involve the modulation of transcriptional and epigenetic profiles.
CELL CHEMICAL BIOLOGY
(2023)
Article
Oncology
Aria Vaishnavi, Joseph Juan, Maebh Jacob, Christopher Stehn, Eric E. Gardner, Michael T. Scherzer, Sophia Schuman, J. Edward Van Veen, Brandon Murphy, Christopher S. Hackett, Adam J. Dupuy, Steven A. Chmura, Louise van der Weyden, Justin Y. Newberg, Annie Liu, Karen Mann, Alistair G. Rust, William A. Weiss, Conan G. Kinsey, David J. Adams, Allie Grossmann, Michael B. Mann, Martin McMahon
Summary: This study identifies RBMS3 as a lung cancer suppressor, showing that silencing RBMS3 promotes the progression of BRAFV600E-driven lung cancer, providing insights for more effective targeting of the disease.