Article
Multidisciplinary Sciences
Paul Basil, Matthew J. Robertson, William E. Bingman, Amit K. Dash, William C. Krause, Ayesha A. Shafi, Badrajee Piyarathna, Cristian Coarfa, Nancy L. Weigel
Summary: The constitutively active androgen receptor splice variant AR-V7 is involved in resistance to androgen deprivation therapy in CRPC. This study compares the activities of AR and AR-V7 using cell lines with matched expression levels. The two isoforms have both shared and distinct transcriptomes and cistromes, with AR-V7 showing unique binding sites.
SCIENTIFIC REPORTS
(2022)
Article
Biochemical Research Methods
Mete Akguen, Nico Pfeifer, Oliver Kohlbacher
Summary: By using secure multi-party computation, this method allows querying genomic databases in a privacy-protected manner, ensuring data privacy, query privacy, and output privacy. It achieves higher efficiency in running queries on large-scale genomic data compared to previous solutions.
Article
Genetics & Heredity
Nadia Waheed, Maryam Naseer, Nighat Haider, Sufyan Suleman, Asmat Ullah
Summary: This study reports a unique case of IL-2R alpha deficiency caused by a novel mutation in a Pakistani family. Clinical whole exome sequencing revealed a new variant, which was interpreted as likely pathogenic. The patient presented with congenital diarrhea, metabolic crisis, and a strong family history of death in infancy due to similar complications.
Article
Genetics & Heredity
Kimia Ghaffari, Lain X. Pierce, Maria Roufaeil, Isabel Gibson, Kevin Tae, Saswat Sahoo, James R. Cantrell, Olov Andersson, Jasmine Lau, Takuya F. Sakaguchi
Summary: In this study, a mutation in the nckap1l gene affecting a short splice isoform was identified as causing specific branching morphogenesis defects in the intrahepatic biliary network in zebrafish. The Nckap1l protein was found to be expressed in biliary epithelial cells, and the mutant gene was shown to interact with the Cdk5 pathway in regulating actin dynamics. The study revealed a previously unappreciated link between hematopoietic and biliary cell lineages, highlighting the role of the minor splice isoform of nckap1l in biliary system formation.
Article
Genetics & Heredity
Ulykbek Kairov, Askhat Molkenov, Aigul Sharip, Saule Rakhimova, Madina Seidualy, Arang Rhie, Ulan Kozhamkulov, Maxat Zhabagin, Jong-Il Kim, Joseph H. Lee, Joseph D. Terwilliger, Jeong-Sun Seo, Zhaxybay Zhumadilov, Ainur Akilzhanova
Summary: Kazakhstan, located along the Great Silk Road, has a rich history and a multiethnic population. By sequencing and analyzing the genomes of five ethnic Kazakhs, this study identified genetic variants associated with higher risks of diseases and demonstrated the importance of genotype-phenotype relations at the population level.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Haijin Zhang, Xue Song, Zongyan Teng, Sujun Cheng, Weigang Yu, Xiaoyi Yao, Zhiqiang Song, Yina Zhang
Summary: The study identified significant differential expression of circRNAs, miRNAs, and mRNAs in peripheral blood samples of male osteoporosis patients, mainly enriched in genes regulating the cell cycle process. The construction of regulatory networks and validation of key circRNAs provide potential biomarkers for the diagnosis and treatment of osteoporosis.
Article
Immunology
Alessandro Didonna, Vincent Damotte, Hengameh Shams, Atsuko Matsunaga, Stacy J. Caillier, Ravi Dandekar, Maneesh K. Misra, Mohammad R. K. Mofrad, Jorge R. Oksenberg, Jill A. Hollenbach
Summary: The acceptor variant in the HLA-DRA gene leads to the transcription of a shorter alpha-chain lacking 25 amino acids, affecting its stability and cellular trafficking. This short isoform of HLA-DRA cannot reach the cell surface, but can bind with the beta-chain and be transported to the cell membrane through interactions with the peptide-binding site of canonical HLA heterodimers.
Article
Biochemical Research Methods
Sander N. Goossens, Tim H. Heupink, Elise De Vos, Anzaan Dippenaar, Margaretha De Vos, Rob Warren, Annelies Van Rie
Summary: The study evaluated the performance of the variant calling tool LoFreq in detecting minor variants in Mycobacterium tuberculosis next generation sequencing data. LoFreq showed high precision and sensitivity in detecting various types and frequencies of minor variants. It can successfully detect minor variant populations and reduce false positive variants due to sequencing errors. The findings can guide future studies in determining the depth of sequencing and the limit of detection in whole genome sequencing data of M. tuberculosis.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Oncology
Vaidehi Jobanputra, Kazimierz O. Wrzeszczynski, Reinhard Buttner, Carlos Caldas, Edwin Cuppen, Sean Grimmond, Torsten Haferlach, Charles Mullighan, Anna Schuh, Olivier Elemento
Summary: Whole-genome and transcriptome sequencing (WGTS) provides new opportunities for identifying and reporting a larger number of potentially actionable alterations in clinical tumor samples. However, these comprehensive tests also come with challenges such as the extent and diversity of sequence alterations and the complexity of interpretation.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Genetics & Heredity
Gabriela Rudd Garces, Maria Elena Turba, Myriam Muracchini, Alessia Diana, Vidhya Jagannathan, Fabio Gentilini, Tosso Leeb
Summary: This study investigated two Dogo Argentino dogs with disproportionate dwarfism, finding evidence suggesting a potential genetic defect in the PKRG2 gene as the likely cause for this phenotype.
Article
Oncology
E. Pleasance, A. Bohm, L. M. Williamson, J. M. T. Nelson, Y. Shen, M. Bonakdar, E. Titmuss, V Csizmok, K. Wee, S. Hosseinzadeh, C. J. Grisdale, C. Reisle, G. A. Taylor, E. Lewis, M. R. Jones, D. Bleile, S. Sadeghi, W. Zhang, A. Davies, B. Pellegrini, T. Wong, R. Bowlby, S. K. Chan, K. L. Mungall, E. Chuah, A. J. Mungall, R. A. Moore, Y. Zhao, B. Deol, A. Fisic, A. Fok, D. A. Regier, D. Weymann, D. F. Schaeffer, S. Young, S. Yip, K. Schrader, N. Levasseur, S. K. Taylor, X. Feng, A. Tinker, K. J. Savage, S. Chia, K. Gelmon, S. Sun, H. Lim, D. J. Renouf, S. J. M. Jones, M. A. Marra, J. Laskin
Summary: This study demonstrates the importance of comprehensive whole-genome and transcriptome sequencing and analysis in guiding personalized cancer therapy, resulting in positive clinical benefits for a significant proportion of patients.
ANNALS OF ONCOLOGY
(2022)
Article
Immunology
Ling Guo, Hongxing Cheng, Shulin Fu, Jun Liu, Yunfei Zhang, Yinsheng Qiu, Hongbo Chen
Summary: This study analyzed the changes in DNA methylome and transcriptome of porcine brain infected with G. parasuis using deep sequencing, and integrated the data to identify key differential methylation regions/sites involved in the regulation of the inflammatory response. The findings showed that the genes inversely correlated with DNA methylation were mainly associated with cell adhesion molecules, bacterial invasion, RIG-1-like receptor signaling pathways, and hematopoietic cell lineage signaling pathways.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Andre E. Minoche, Ben Lundie, Greg B. Peters, Thomas Ohnesorg, Mark Pinese, David M. Thomas, Andreas Zankl, Tony Roscioli, Nicole Schonrock, Sarah Kummerfeld, Leslie Burnett, Marcel E. Dinger, Mark J. Cowley
Summary: ClinSV is a WGS-based framework for integration, annotation, prioritization, and visualization of structural variants with low false positive rates and high reproducibility. In clinical practice, ClinSV identified reportable variants that were undetectable by current clinical microarray designs in a significant percentage of cases.
Article
Oncology
Jessica Wagner, Elizabeth Wickman, Timothy Shaw, Alejandro Allo Anido, Deanna Langfitt, Jinghui Zhang, Shaina N. Porter, Shondra M. Pruett-Miller, Heather Tillman, Giedre Krenciute, Stephen Gottschalk
Summary: Targeting tumor-specific splice variants such as EDB with CAR T cells is feasible and has the potential to improve the efficacy of CAR T-cell therapy.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Wan He, Shaowei Dong, Jing Shen, Jiutong Wu, Pan Zhao, Dongbing Li, Dongliang Wang, Na Tang, Chang Zou
Summary: In this study, the molecular characteristics of a Chinese family with Lynch syndrome were explored using whole genome sequencing. Mutations in MMR related genes, as well as other DNA repair pathways, were found to be enhanced in this family. Specific variants in MSH2 and FSHR were identified and their potential implications for therapy were discussed. These findings contribute to the understanding of Lynch syndrome and have important implications for future screening and diagnosis.
FRONTIERS IN ONCOLOGY
(2023)
Article
Immunology
Dario F. Marzella, Farzaneh M. Parizi, Derek Van Tilborg, Nicolas Renaud, Daan Sybrandi, Rafaella Buzatu, Daniel T. Rademaker, Peter A. C. 't Hoen, Li C. Xue
Summary: A deeper understanding of T-cell-mediated adaptive immune responses is crucial for cancer immunotherapy and antiviral vaccine design. Researchers have developed PANDORA, a generic modelling pipeline for pMHC-I and pMHC-II, which shows excellent performance in pMHC-I modelling.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
K. Joeri van der Velde, Gurnoor Singh, Rajaram Kaliyaperumal, Xiaofeng Liao, Sander de Ridder, Susanne Rebers, Hindrik H. D. Kerstens, Fernanda de Andrade, Jeroen van Reeuwijk, Fini E. De Gruyter, Saskia Hiltemann, Maarten Ligtvoet, Marjan M. Weiss, Hanneke W. M. van Deutekom, Anne M. L. Jansen, Andrew P. Stubbs, Lisenka E. L. M. Vissers, Jeroen F. J. Laros, Esther van Enckevort, Daphne Stemkens, Peter A. C. t Hoen, Jeroen A. M. Belien, Marielle E. van Gijn, Morris A. Swertz
Summary: FAIR Genomes aims to facilitate the reuse of genomic data by developing metadata standards and providing templates for data entry and programmatic interfaces. It addresses the challenge of storing and sharing genomic data by offering a semantic schema for data descriptions. With FAIR Genomes, rare disease diagnosis and personalized medicine research can be enhanced.
Article
Mathematical & Computational Biology
Renee X. de Menezes, Armin Rauschenberger, Bios Consortium, Peter A. C. 't Hoen, Marianne A. Jonker
Summary: This article introduces a score-based test method that takes into account the effects of all exons and all SNPs on exon inclusion simultaneously. The test method is computationally efficient and can be used when the number of SNPs is larger than the number of samples. It is also more robust to exon-SNP pair-specific effects.
BIOMETRICAL JOURNAL
(2023)
Article
Biotechnology & Applied Microbiology
Anna Niehues, Daniele Bizzarri, Marcel J. T. Reinders, P. Eline Slagboom, Alain J. van Gool, Erik B. van den Akker, Peter A. C. 't Hoen
Summary: Population-scale expression profiling studies provide valuable insights into biological and disease mechanisms. Missing or incomplete phenotypic information can hinder data analysis. Metabolomics-based surrogates can be used as predictors for clinical phenotypes. In this study, metabolomic surrogates were evaluated for 17 traits using expression profiling data. The results showed that metabolomic surrogates performed similarly to reported phenotypes.
Article
Biochemistry & Molecular Biology
Emanuela Oldoni, Gary Saunders, Florence Bietrix, Maria Laura Garcia Bermejo, Anna Niehues, Peter A. C. 't Hoen, Jessica Nordlund, Marian Hajduch, Andreas Scherer, Katja Kivinen, Esa Pitkanen, Tomi Pekka Makela, Ivo Gut, Serena Scollen, Lukasz Kozera, Manel Esteller, Leming Shi, Anton Ussi, Antonio L. Andreu, Alain J. van Gool
Summary: Personalised medicine (PM) offers a great opportunity to enhance individualized healthcare. Advances in -omics technologies have enabled the study of complex human diseases, supporting the development of PM. This article summarizes the outcomes of a workshop that aimed to outline common promises and challenges in multi-omics research, assess the potential of new technologies like artificial intelligence, and foster collaboration between key initiatives.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Hematology
W. Huisman, M. C. J. Roex, L. Hageman, E. A. S. Koster, S. A. J. Veld, C. Hoogstraten, P. van Balen, H. M. van Egmond, C. A. M. van Bergen, H. Einsele, L. Germeroth, D. Amsen, J. H. F. Falkenburg, I. Jedema
Summary: Adoptive cellular therapies with T cells are increasingly used to treat various conditions. In this study, we demonstrated the expansion and persistence of virus-specific T cells from prophylactically infused multiantigen-specific T-cell products. By using mRNA sequencing, we were able to track the fate of the transferred T-cell populations and distinguish them from recipient- or stem cell graft-derived T cells.
Meeting Abstract
Hematology
Troy Noordenbos, Fleur A. De Groot, Ruben A. L. De Groen, Lorraine M. De Haan, Ricki T. Krog, Aniko Sijs-Szabo, Marieke Griffioen, Rosa de Groot, Mirjam H. M. Heemskerk, Marieke E. Ijsselsteijn, Valeska Terpstra, Marcel Nijland, Pim Mutseaers, Martine E. D. Chamuleau, Marie Jose Kersten, Arjan Diepstra, Judith Bovee, Patty M. Jansen, Noel F. C. C. De Miranda, Joost S. P. Vermaat
Meeting Abstract
Hematology
Georgia Koutsoumpli, Dyantha van der Lee, Nina C. Groenland, M. Willy Honders, Rob C. M. de Jong, Renate S. Hagedoorn, Hendrik Veelken, Peter A. van Veelen, Dominik Lock, Mirjam H. M. Heemskerk, J. H. Frederik Falkenburg, Ian Johnston, Marieke Griffioen
Meeting Abstract
Hematology
Kyra J. Fuchs, M. Willy Honders, Marian van de Meent, Indu Khatri, Eva A. S. Koster, Cornelis A. M. van Bergen, Erik B. van den Akker, Constantijn J. M. Halkes, J. H. Frederik Falkenburg, Marieke Griffioen
Meeting Abstract
Hematology
Miranda H. Meeuwsen, Anne K. Wouters, Tassilo L. A. Wachsmann, Renate S. Hagedoorn, Michel G. D. Kester, Dennis F. G. Remst, Dirk M. van der Steen, Arnoud H. de Ru, Els P. van Hees, Marieke Griffioen, Peter A. van Veelen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Article
Biology
Tooba Abbassi-Daloii, Salma el Abdellaoui, Lenard M. Voortman, Thom T. J. Veeger, Davy Cats, Hailiang Mei, Duncan E. Meuffels, Ewoud van Arkel, Peter Bram 't Hoen, Hermien Kan, Vered Raz
Summary: We constructed a large atlas of RNA-seq profiles from leg muscles, identifying differential expression patterns and cellular composition across different tissues. The muscle samples were clustered into three groups based on anatomical location, which were associated with oxidative metabolism and fast- or slow-twitch myofibers. Expression profiles of Homeobox transcription factors differed between the three groups. Our study provides a novel resource to study muscle-specific molecular features and their potential links to physiological processes.
Article
Oncology
Miranda H. Meeuwsen, Anne K. Wouters, Tassilo L. A. Wachsmann, Renate S. Hagedoorn, Michel G. D. Kester, Dennis F. G. Remst, Dirk M. van der Steen, Arnoud H. de Ru, Els P. van Hees, Martijn Kremer, Marieke Griffioen, Peter A. van Veelen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: Jchain is highly expressed in multiple myeloma (MM) and Jchain-derived peptides presented in HLA molecules may be suitable antigens for T-cell therapy of MM. Using immunopeptidomics, Jchain-derived epitopes presented by MM cells were identified, and Jchain-specific T-cell clones were isolated using pHLA tetramer technology. TCRs targeting Jchain-derived peptides presented in four common HLA alleles demonstrated potent preclinical anti-myeloma activity, encouraging further preclinical testing and ultimately clinical development.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Biochemical Research Methods
Samuel Bernardo-Bermejo, Jingchuan Xue, Linh Hoang, Elizabeth Billings, Bill Webb, M. Willy Honders, Sanne Venneker, Bram Heijs, Maria Castro-Puyana, Maria Luisa Marina, Erik B. van den Akker, Marieke Griffioen, Gary Siuzdak, Martin Giera, Elena Sanchez-Lopez
Summary: Analytical techniques with high sensitivity and selectivity are crucial in clinical sample analysis. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is the standard method, but it is expensive. This study demonstrates that similar results can be achieved using a simpler single mass spectrometry detector combined with enhanced in-source fragmentation/annotation and correlated ion monitoring. The protocol provides step-by-step instructions for optimizing the conditions for this technique, making it broadly applicable and cost-effective for quantifying small molecules.
Article
Biochemistry & Molecular Biology
Jesper van Eck van der Sluijs, Diede van Ens, Jolanda Brummelman, Daan Heister, Aastha Sareen, Lisa Truijen, Dorette S. van Ingen Schenau, Mirjam H. M. Heemskerk, Marieke Griffioen, Michel G. D. Kester, Nicolaas P. M. Schaap, Joop H. Jansen, Anniek B. van der Waart, Harry Dolstra, Willemijn Hobo
Summary: Non-DCs have been found to enhance the activation and expansion of antigen-specific CD8+ T cells mediated by DCs, without impairing the NK cell responses in vitro and in vivo. This provides a rationale for further clinical translation of the CD34+-derived DC-complete vaccine in hemato-oncology patients post alloSCT.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Letter
Oncology
Paul J. Hengeveld, Hendrik Veelken, Cornelis A. M. van Bergen, Edwin Quinten, Mischa Y. L. Vervoordeldonk, Wahija Ismailzada, Rob S. Barendse, Julie M. N. Dubois, Marinus H. J. van Oers, Christian H. Geisler, Arnon P. Kater, Peter E. Westerweel, Anton W. Langerak, Mark-David Levin