Article
Computer Science, Information Systems
Tian Zheng, Xinyang Qian, Jiayin Wang
Summary: This paper introduces a transfer learning-based method to accurately genotype structural variations while considering copy number variations (CNVs). By adjusting the weights of instances with different allelic copy numbers, the method maximizes the contribution of all instances to genotyping and minimizes the genotyping errors caused by CNVs.
FRONTIERS OF COMPUTER SCIENCE
(2022)
Article
Health Care Sciences & Services
Mazen A. A. Atiq, Sandra E. E. Peterson, Loralie J. J. Langman, Linnea M. M. Baudhuin, John L. L. Black, Ann M. M. Moyer
Summary: CYP2D6 duplication has pharmacogenomic implications and the duplicated allele can be reliably determined using real-time PCR-based genotyping with copy number variation (CNV) detection.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Agriculture, Dairy & Animal Science
Nora Laseca, Antonio Molina, Mercedes Valera, Alicia Antonini, Sebastian Demyda-Peyras
Summary: This study provides a detailed characterization of CNV regions in the Pura Raza Espanola horse breed, revealing a unique pattern of genomic regions enriched in CNVs and the incidence of CNVs across the entire genome. The study also identifies genes related to olfactory pathways and immune response. The findings contribute to our understanding of CNVs in equines and their impact on genetic and phenotypic variations.
Article
Biochemistry & Molecular Biology
Thomas F. Eleveld, Chaimaa Bakali, Paul P. Eijk, Phylicia Stathi, Lianne E. Vriend, Pino J. Poddighe, Bauke Ylstra
Summary: Large-scale chromosomal deletions are common in cancer and confer an oncogenic advantage, but the oncogenic drivers behind these deletions are difficult to identify. This study introduced a novel CRISPR-Cas9 technique to engineer large-scale deletions and create isogenic cell line models, successfully inducing deletions in neuroblastoma cell lines. The technique may provide valuable insights into the role of large-scale deletions in tumor development and growth.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
D. K. Wosniaki, A. M. Marin, G. S. Soares, D. L. Zanette, L. Blanes, E. C. Munhoz, M. Aoki
Summary: Deletion of GSTM1 and GSTT1 genes may cause reduced glutathione S-transferase activity, leading to increased risk of leukemia. The frequency of GSTM1-null and GSTT1-null genotypes was significantly higher in Brazilian leukemia patients, especially in chronic leukemia.
GENETICS AND MOLECULAR RESEARCH
(2022)
Article
Immunology
Shalini Nair, Xue Li, Standwell C. Nkhoma, Tim Anderson
Summary: This study investigates the fitness costs of parasites carrying pfhrp2 and/or pfhrp3 deletions through gene editing. The results show significant fitness costs for pfhrp2 deletion and pfhrp2/3 double deletion, comparable to those resulting from drug resistance mutations. These findings may explain the increasing frequency of pfhrp deletions in certain locations but not in others.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Review
Biochemistry & Molecular Biology
Vincenza Ylenia Cusenza, Alessandra Bisagni, Monia Rinaldini, Chiara Cattani, Raffaele Frazzi
Summary: Cytogenetic and molecular assessments play crucial roles in the diagnosis and treatment of cancer. Laboratory approaches like multiplex ligation-dependent probe amplification and droplet digital PCR are exceptional tools for detecting genetic alterations accurately and sensitively in molecular oncology. Personalized medicine relies on the correct and reliable molecular characterization of diseases, influencing therapeutic choices.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
Jens Borggaard Larsen, Steffen Jorgensen
Summary: Genotyping of the CYP2D6 gene is a widely used pharmacogenetic test globally, and this study presents two simple novel methods for identifying deletions or duplications of the CYP2D6 gene. These methods, namely relative quantification using a singleplex 5' nuclease real-time PCR assay and high-resolution melting of PCR products, have been validated against a reference method using a large set of samples. The results show that these methods offer robust identification of gene deletions and duplications.
Article
Biochemical Research Methods
Luca Denti, Parsoa Khorsand, Paola Bonizzoni, Fereydoun Hormozdiari, Rayan Chikhi
Summary: Structural variants (SVs) contribute to sequence variability in genomes and are significant in human genomics and precision medicine. However, due to the complexities of the human genome, SV discovery in individuals has been challenging. The introduction of low-error long-read sequencing technologies, such as PacBio HiFi, may provide a solution to these challenges.
Article
Agriculture, Dairy & Animal Science
Giada Santa Calogero, Marta Giuga, Vera D'Urso, Venera Ferrito, Anna Maria Pappalardo
Summary: In this study, the evaluation of mtDNAcn variation was applied for the first time to Opsius heydeni individuals, showing a decrease in mtDNAcn in specimens from the polluted site. These findings suggest that environmental contaminants can alter the mitochondrial genome and Opsius heydeni could serve as a potential bioindicator species of environmental quality.
Article
Biochemical Research Methods
Junping Li, Lin Gao, Yusen Ye
Summary: The researchers developed a control-free method called HiSV for identifying large-scale structural variations from Hi-C samples. HiSV achieved superior accuracy and sensitivity through evaluations on simulated data sets and cancer cell lines, and effectively captured complex SVs. HiSV can also supplement the results of WGS methods.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biology
Milovan Suvakov, Arijit Panda, Colin Diesh, Ian Holmes, Alexej Abyzov
Summary: CNVpytor is an extension of CNVnator that improves performance and functionality, allowing for filtering, annotation, and merging of CNV calls across multiple samples. Its modular architecture enables use in shared and cloud environments, and data can be exported to JBrowse for visualization and analysis.
Article
Biochemical Research Methods
Xia Wang, Dechun Xing, Zheng Liu, Yujing Zhang, Bo Cheng, Suozhu Sun, Qingtao Wang, Lianhua Dong
Summary: Accurate measurement of HER2 copy number variation is crucial for guiding tumor target therapy in breast cancer. Digital PCR (dPCR) is a sensitive and quantitative method that can detect HER2 CNV. The study established and validated three HER2 exon-specific dPCR assays along with three new reference gene assays, which showed high concordance rates with the diagnostic results of clinical FFPE samples by fluorescence in situ hybridization (FISH). The proposed dPCR method accurately provides the absolute copy number of HER2 and reference genes, improving molecular typing and diagnosis of breast cancer.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2023)
Article
Veterinary Sciences
Ciro D. Cordeiro, Nesim Gonceer, Steve Dorus, James E. Crill, Vardit Moshayoff, Amit Lachman, Asaf Moran, Dan Vilenchik, Shlomit Fedida-Metula
Summary: The demand for poultry meat and eggs is growing consistently, and there is a pressing need for improved protocols to determine chicken sex, especially in the layer industry. Extensive efforts are being made to develop in-ovo sexing detection methods to avoid the culling of male chicks. In this study, a fast, cost-effective, and accurate method for genotyping sex chromosomes in chickens using small volumes of blood was developed and validated.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Article
Oncology
Bart Vrugt, Michaela B. Kirschner, Mayura Meerang, Kathrin Oehl, Ulrich Wagner, Alex Soltermann, Holger Moch, Isabelle Opitz, Peter J. Wild
Summary: In this study, the suitability of using p16 and MTAP IHC for detecting CDKN2A deletion in pleural mesothelioma was investigated. The results showed that MTAP and p16 IHC had high sensitivity and specificity for detecting any gene loss, and had high concordance with OncoScan CNV arrays.
Article
Multidisciplinary Sciences
Christopher J. Hanley, Sara Waise, Matthew J. Ellis, Maria A. Lopez, Wai Y. Pun, Julian Taylor, Rachel Parker, Lucy M. Kimbley, Serena J. Chee, Emily C. Shaw, Jonathan West, Aiman Alzetani, Edwin Woo, Christian H. Ottensmeier, Matthew J. J. Rose-Zerilli, Gareth J. Thomas
Summary: Through single cell RNA-sequencing, multiplexed immunohistochemistry, and digital cytometry, three major fibroblast subpopulations in non-small cell lung cancer are identified and characterised. These subpopulations include adventitial, alveolar, and myofibroblasts. Myofibroblasts are associated with poor overall survival rates in lung adenocarcinomas, while their presence in squamous carcinomas does not have a prognostic value. These findings have important implications for the development of fibroblast-targeting strategies in cancer therapy.
NATURE COMMUNICATIONS
(2023)
Article
Allergy
Ali H. Ziyab, John W. Holloway, Yaser M. Ali, Hongmei Zhang, Wilfried Karmaus
Summary: This study aimed to estimate the prevalence of eczema symptoms and severity among adolescents in Kuwait, and assess the frequency of eczema-related nocturnal sleep disturbance and its relation to antihistamine use. The results showed that the prevalence of current eczema was 10.2%, and 12.7% of participants experienced sleep disturbance due to eczema more than once a week. Factors associated with eczema prevalence included underweight body mass index, Cesarean section delivery, and parental history of eczema.
WORLD ALLERGY ORGANIZATION JOURNAL
(2023)
Article
Immunology
Carly A. Bobak, Maresa Botha, Lesley Workman, Jane E. Hill, Mark P. Nicol, John W. Holloway, Dan J. Stein, Leonardo Martinez, Heather J. Zar
Summary: This study investigated the relationship between gene expression in umbilical cord blood and the risk of developing tuberculosis (TB) infection and disease in early life. Gene expression signatures were identified that were predictive of TB conversion and progression to TB disease in children with early infection. Coexpression network analysis revealed modules associated with neutrophil activation and defense responses to bacteria. These findings provide novel insights into TB pathogenesis and susceptibility.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Obstetrics & Gynecology
Shiao-Yng Chan, Sheila J. Barton, See Ling Loy, Hsin Fang Chang, Philip Titcombe, Jui-Tsung Wong, Marilou Ebreo, Judith Ong, Karen ML. Tan, Heidi Nield, Sarah El -Heis, Timothy Kenealy, Yap-Seng Chong, Philip N. Baker, Wayne S. Cutfield, Keith M. Godfrey
Summary: This study examined the impact of a combined myo-inositol, probiotics, and micronutrient nutritional supplement on time-to-natural-conception and clinical pregnancy rates. The results showed that there was no significant difference in time-to-natural-conception and clinical pregnancy rates within a year between women receiving the supplement and those in the control group. Overweight women had a longer time-to-conception, but the supplement may shorten their time-to-conception to that comparable to nonoverweight/nonobese women.
FERTILITY AND STERILITY
(2023)
Review
Medicine, General & Internal
Cecilie Svanes, John W. W. Holloway, Susanne Krauss-Etschmann
Summary: Emerging research suggests that exposures occurring years before conception are important determinants of the health of future offspring and subsequent generations. There is increasing evidence that respiratory health is influenced by parental exposures that occur long before conception, such as adolescent tobacco smoking and overweight in future fathers. These exposures have been linked to increased asthma and lower lung function in their offspring. Understanding the potential impact of parental exposures on the health of future generations can lead to the development of preventive strategies and break the cycle of health inequalities across generations.
JOURNAL OF INTERNAL MEDICINE
(2023)
Review
Allergy
Merlijn van Breugel, Rudolf S. N. Fehrmann, Marnix Buegel, Faisal I. Rezwan, John W. Holloway, Martijn C. Nawijn, Sara Fontanella, Adnan Custovic, Gerard H. Koppelman
Summary: The field of medicine is increasingly interested in artificial intelligence (AI), which allows for new research questions and analysis of larger and different types of data. However, there are few applications of AI in the field of allergy that go beyond proof of concepts and provide clinical value. This review provides an understanding of AI concepts, discusses limitations and challenges such as data availability and bias, and explores potential directions to overcome them. It also presents case examples of AI applications in allergy, with a focus on diagnosis and subtyping. The review shares guidelines for good AI practice, prospects for field advancement, and initiatives to increase clinical impact, highlighting the potential of AI in deepening our understanding of disease mechanisms and contributing to precision medicine in allergy.
Letter
Allergy
Aniruddha Rathod, Rajesh Melaram, Hongmei Zhang, Hasan Arshad, Susan Ewart, Meredith Ray, Caroline L. Relton, Wilfried Karmaus, John W. Holloway
CLINICAL AND EXPERIMENTAL ALLERGY
(2023)
Article
Multidisciplinary Sciences
Ashley Budu-Aggrey, Anna Kilanowski, Maria K. Sobczyk, Suyash S. Shringarpure, Ruth Mitchell, Kadri Reis, Anu Reigo, Reedik Maegi, Mari Nelis, Nao Tanaka, Ben M. Brumpton, Laurent F. Thomas, Pol Sole-Navais, Christopher Flatley, Antonio Espuela-Ortiz, Esther Herrera-Luis, Jesus V. T. Lominchar, Jette Bork-Jensen, Ingo Marenholz, Aleix Arnau-Soler, Ayoung Jeong, Katherine A. Fawcett, Hansjorg Baurecht, Elke Rodriguez, Alexessander Couto Alves, Ashish Kumar, Patrick M. Sleiman, Xiao Chang, Carolina Medina-Gomez, Chen Hu, Cheng-jian Xu, Cancan Qi, Sarah El-Heis, Philip Titcombe, Elie Antoun, Joao Fadista, Carol A. Wang, Elisabeth Thiering, Baojun Wu, Sara Kress, Dilini M. Kothalawala, Latha Kadalayil, Jiasong Duan, Hongmei Zhang, Sabelo Hadebe, Thomas Hoffmann, Eric Jorgenson, Helene Choquet, Neil Risch, Pal Njolstad, Ole A. Andreassen, Stefan Johansson, Catarina Almqvist, Tong Gong, Vilhelmina Ullemar, Robert Karlsson, Patrik K. E. Magnusson, Agnieszka Szwajda, Esteban G. Burchard, Jacob P. Thyssen, Torben Hansen, Line L. Karhus, Thomas M. Dantoft, Alexander C. S. N. Jeanrenaud, Ahla Ghauri, Andreas Arnold, Georg Homuth, Susanne Lau, Markus M. Noethen, Norbert Huebner, Medea Imboden, Alessia Visconti, Mario Falchi, Veronique Bataille, Pirro Hysi, Natalia Ballardini, Dorret I. Boomsma, Jouke J. Hottenga, Martina Mueller-Nurasyid, Tarunveer S. Ahluwalia, Jakob Stokholm, Bo Chawes, Ann-Marie M. Schoos, Ana Esplugues, Mariona Bustamante, Benjamin Raby, Syed Arshad, Chris German, Tonu Esko, Lili A. Milani, Andres Metspalu, Chikashi Terao, Katrina Abuabara, Mari Loset, Kristian Hveem, Bo Jacobsson, Maria Pino-Yanes, David P. Strachan, Niels Grarup, Allan Linneberg, Young-Ae Lee, Nicole Probst-Hensch, Stephan Weidinger, Marjo-Riitta Jarvelin, Erik Melen, Hakon Hakonarson, Alan D. Irvine, Deborah Jarvis, Tamar Nijsten, Liesbeth Duijts, Judith M. Vonk, Gerard H. Koppelmann, Keith M. Godfrey, Sheila J. Barton, Bjarke Feenstra, Craig E. Pennell, Peter D. Sly, Patrick G. Holt, L. Keoki Williams, Hans Bisgaard, Klaus Bonnelykke, John Curtin, Angela Simpson, Clare Murray, Tamara Schikowski, Supinda Bunyavanich, Scott T. Weiss, John W. Holloway, Josine L. Min, Sara J. Brown, Marie Standl, Lavinia Paternoster
Summary: This study conducted the largest genome-wide association study (GWAS) on atopic dermatitis (AD) to date, identifying 81 replicated AD-associated loci in Europeans and 10 additional loci in a multi-ancestry analysis. The implicated genes are predominantly involved in immune pathways relevant to atopic inflammation and may offer drug repurposing opportunities.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Latha Kadalayil, Md. Zahangir Alam, Cory Haley White, Akram Ghantous, Esther Walton, Olena Gruzieva, Simon Kebede Merid, Ashish Kumar, Ritu P. Roy, Olivia Solomon, Karen Huen, Brenda Eskenazi, Peter Rzehak, Veit Grote, Jean-Paul Langhendries, Elvira Verduci, Natalia Ferre, Darek Gruszfeld, Lu Gao, Weihua Guan, Xuehuo Zeng, Enrique F. Schisterman, John F. Dou, Kelly M. Bakulski, Jason I. Feinberg, Munawar Hussain Soomro, Giancarlo Pesce, Nour Baiz, Elena Isaevska, Michelle Plusquin, Marina Vafeiadi, Theano Roumeliotaki, Sabine A. S. Langie, Arnout Standaert, Catherine Allard, Patrice Perron, Luigi Bouchard, Evelien R. van Meel, Janine F. Felix, Vincent W. V. Jaddoe, Paul D. Yousefi, Cecilia H. Ramlau-Hansen, Caroline L. Relton, Elmar W. Tobi, Anne P. Starling, Ivana V. Yang, Maria Llambrich, Gillian Santorelli, Johanna Lepeule, Lucas A. Salas, Mariona Bustamante, Susan L. Ewart, Hongmei Zhang, Wilfried Karmaus, Stefan Roeder, Ana Claudia Zenclussen, Jianping Jin, Wenche Nystad, Christian M. Page, Maria Magnus, Dereje D. Jima, Cathrine Hoyo, Rachel L. Maguire, Tuomas Kvist, Darina Czamara, Katri Raikkonen, Tong Gong, Vilhelmina Ullemar, Sheryl L. Rifas-Shiman, Emily Oken, Catarina Almqvist, Robert Karlsson, Jari Lahti, Susan K. Murphy, Siri E. Haberg, Stephanie London, Gunda Herberth, Hasan Arshad, Jordi Sunyer, Regina Grazuleviciene, Dana Dabelea, Regine P. M. Steegers-Theunissen, Ellen A. Nohr, Thorkild I. A. Sorensen, Liesbeth Duijts, Marie-France Hivert, Vera Nelen, Maja Popovic, Manolis Kogevinas, Tim S. Nawrot, Zdenko Herceg, Isabella Annesi-Maesano, M. Daniele Fallin, Edwina Yeung, Carrie V. Breton, Berthold Koletzko, Nina Holland, Joseph L. Wiemels, Erik Melen, Gemma C. Sharp, Matt J. Silver, Faisal Rezwan, John W. Holloway
Summary: This study found significant associations between DNA methylation and birth season at birth and in childhood. The differential methylation regions (DMRs) identified were related to genes involved in tumorigenesis, psychiatric/neurological disorders, inflammation, and immunity. Furthermore, the associations between birth season and DNA methylation were influenced by birth latitude, particularly in higher latitude regions.
CLINICAL EPIGENETICS
(2023)
Article
Oncology
Negusse Tadesse Kitaba, Gerd Toril Morkve Knudsen, Ane Johannessen, Faisal I. Rezwan, Andrei Malinovschi, Anna Oudin, Bryndis Benediktsdottir, David Martino, Francisco Javier Callejas Gonzalez, Leopoldo Palacios Gomez, Mathias Holm, Nils Oskar Jogi, Shyamali C. Dharmage, Svein Magne Skulstad, Sarah H. Watkins, Matthew Suderman, Francisco Gomez-Real, Vivi Schlunssen, Cecilie Svanes, John W. Holloway
Summary: Experimental studies suggest that paternal preconception smoking can affect respiratory health in the offspring through epigenetic changes. This study found that paternal preconception smoking is associated with DNA methylation in the offspring, and these differentially methylated sites are linked to gene silencing. Some of these sites are also associated with offspring outcomes such as asthma, wheezing, weight, and BMI.
CLINICAL EPIGENETICS
(2023)
Article
Genetics & Heredity
Parnian Kheirkhah Rahimabad, A. Daniel Jones, Hongmei Zhang, Su Chen, Yu Jiang, Susan Ewart, John W. Holloway, Hasan Arshad, Shakiba Eslamimehr, Robert Bruce, Wilfried Karmaus
Summary: This study aimed to investigate whether polymorphisms in GST genes influence the effect of MSP on offspring DNAm. The results showed that in males, GST gene polymorphisms modified the associations between hydroxycotinine and DNAm, as well as between norcotinine and DNAm. In females, GST gene polymorphisms also modified the associations between hydroxycotinine and DNAm, as well as between norcotinine and DNAm. This study highlights the role of genetic polymorphism in GST genes in the susceptibility of DNAm to MSP.
Article
Medicine, General & Internal
Keith M. Godfrey, Philip Titcombe, Sarah El-Heis, Benjamin B. Albert, Elizabeth Huiwen Tham, Sheila J. Barton, Timothy Kenealy, Mary Foong-Fong Chong, Heidi Nield, Yap Seng Chong, Shiao-Yng Chan, Wayne S. Cutfield
Summary: The study found that taking prenatal/pregnancy vitamin supplements can significantly reduce the incidence of vitamin deficiency and depletion before and during pregnancy, and also helps to maintain higher levels of vitamin B12 in maternal plasma during the recommended lactational period.
Article
Dermatology
Sadia Haider, Raquel Granell, John A. Curtin, John W. Holloway, Sara Fontanella, Syed Hasan Arshad, Clare S. Murray, Paul Cullinan, Stephen Turner, Graham Roberts, Angela Simpson, Adnan Custovic
Summary: This study provides a comprehensive description of the longitudinal pattern of symptoms in eczema through childhood. By using multidimensional variables and clustering analysis, stable clusters with different genetic characteristics were identified. The study also found differences in the association with risk factors and FLG mutations among different clusters.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Meeting Abstract
Respiratory System
N. Kitaba, T. Knudsen, A. Johannessen, F. Rezwan, A. Malinovschi, A. Oudin, B. Benediktsdottir, D. Martino, F. Callejas Gonzalez, L. Gomez, M. Holm, O. Jogi, S. Shyamali Dharmage, S. Skulstad, F. Gomez-Real, V Schlunssen, C. Svanes, J. Holloway
EUROPEAN RESPIRATORY JOURNAL
(2022)