We propose a new method for multivariate response regression and covariance estimation when elements of the response vector are of mixed types, for example some continuous and some discrete. Our method is based on a model which assumes the observable mixed-type response vector is connected to a latent multivariate normal response linear regression through a link function. We explore the properties of this model and show its parameters are identifiable under reasonable conditions. We impose no parametric restrictions on the covariance of the latent normal other than positive definiteness, thereby avoiding assumptions about unobservable variables which can be difficult to verify in practice. To accommodate this generality, we propose a novel algorithm for approximate maximum likelihood estimation that works "off-the-shelf" with many different combinations of response types, and which scales well in the dimension of the response vector. Our method typically gives better predictions and parameter estimates than fitting separate models for the different response types and allows for approximate likelihood ratio testing of relevant hypotheses such as independence of responses. The usefulness of the proposed method is illustrated in simulations; and one biomedical and one genomic data example.
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http://dx.doi.org/10.1002/sim.9383 | DOI Listing |
Commun Biol
January 2025
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Aedes mosquitoes transmit pathogenic arthropod-borne (arbo) viruses, putting nearly half the world's population at risk. Blocking virus replication in mosquitoes is a promising approach to prevent arbovirus transmission, the development of which requires in-depth knowledge of virus-host interactions and mosquito immunity. By integrating multi-omics data, we find that heat shock factor 1 (Hsf1) regulates eight small heat shock protein (sHsp) genes within one topologically associated domain in the genome of the Aedes aegypti mosquito.
View Article and Find Full Text PDFInflamm Res
January 2025
Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, No.127 Changle West Road, Xincheng District, Xi'an, 710032, Shaanxi, China.
Background: Hypertrophic scar (HS) is a severe skin fibrosis. Transplanting stem cells carrying anti-fibrotic cytokine genes, like interferon-gamma (IFN-γ), is a novel therapeutic strategy. Human amniotic epithelial cells (hAECs) are ideal seed cells and gene vectors.
View Article and Find Full Text PDFViruses
January 2025
Surgical Neurology Branch, NINDS, NIH 10 Center Drive, Bethesda, MD 20892, USA.
Glioblastoma multiforme (GBM) is a devastating, aggressive primary brain tumor with poor patient outcomes and a five-year survival of less than 10%. Significant limitations to effective GBM treatment include poor drug delivery across the blood-brain barrier, drug resistance, and complex genetic tumor alterations. Gene therapy uses a mechanism different from other GBM therapies to reduce tumor growth and enhance antitumor immunity.
View Article and Find Full Text PDFPharmaceutics
January 2025
Key Laboratory of Molecular Biophysics, Institute of Biophysics, School of Health Sciences & Biomedical Engineering, Hebei University of Technology, Tianjin 300401, China.
Brain diseases pose significant treatment challenges due to the restrictive nature of the blood-brain barrier (BBB). Recent advances in targeting macromolecules offer promising avenues for overcoming these obstacles through receptor-mediated transcytosis (RMT). We summarize the current progress in targeting brain drug delivery with macromolecules for brain diseases.
View Article and Find Full Text PDFPharmaceutics
January 2025
NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100005, China.
Background: The Epstein-Barr virus (EBV) is intricately linked to a range of human malignancies, with EBV latent membrane protein 2A (LMP2A) emerging as a potential target antigen for immunotherapeutic strategies in the treatment of nasopharyngeal carcinoma (NPC).
Methods: The modified vaccinia virus Ankara (MVA) is universally used in vector vaccine research because of its excellent safety profile and highly efficient recombinant gene expression. Here, we constructed a novel MVA-LMP2A recombinant virus and investigated its specific immune response induction and oncolytic effect.
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