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2022 ◽  
Vol 12 (1) ◽  
Author(s):  
P. Zacharopoulou ◽  
E. Marchi ◽  
A. Ogbe ◽  
N. Robinson ◽  
H. Brown ◽  
...  

AbstractAlthough certain individuals with HIV infection can stop antiretroviral therapy (ART) without viral load rebound, the mechanisms under-pinning ‘post-treatment control’ remain unclear. Using RNA-Seq we explored CD4 T cell gene expression to identify evidence of a mechanism that might underpin virological rebound and lead to discovery of associated biomarkers. Fourteen female participants who received 12 months of ART starting from primary HIV infection were sampled at the time of stopping therapy. Two analysis methods (Differential Gene Expression with Gene Set Enrichment Analysis, and Weighted Gene Co-expression Network Analysis) were employed to interrogate CD4+ T cell gene expression data and study pathways enriched in post-treatment controllers versus early rebounders. Using independent analysis tools, expression of genes associated with type I interferon responses were associated with a delayed time to viral rebound following treatment interruption (TI). Expression of four genes identified by Cox-Lasso (ISG15, XAF1, TRIM25 and USP18) was converted to a Risk Score, which associated with rebound (p < 0.01). These data link transcriptomic signatures associated with innate immunity with control following stopping ART. The results from this small sample need to be confirmed in larger trials, but could help define strategies for new therapies and identify new biomarkers for remission.


2022 ◽  
Author(s):  
Martin Treppner ◽  
Harald Binder ◽  
Moritz Hess

AbstractDeep generative models can learn the underlying structure, such as pathways or gene programs, from omics data. We provide an introduction as well as an overview of such techniques, specifically illustrating their use with single-cell gene expression data. For example, the low dimensional latent representations offered by various approaches, such as variational auto-encoders, are useful to get a better understanding of the relations between observed gene expressions and experimental factors or phenotypes. Furthermore, by providing a generative model for the latent and observed variables, deep generative models can generate synthetic observations, which allow us to assess the uncertainty in the learned representations. While deep generative models are useful to learn the structure of high-dimensional omics data by efficiently capturing non-linear dependencies between genes, they are sometimes difficult to interpret due to their neural network building blocks. More precisely, to understand the relationship between learned latent variables and observed variables, e.g., gene transcript abundances and external phenotypes, is difficult. Therefore, we also illustrate current approaches that allow us to infer the relationship between learned latent variables and observed variables as well as external phenotypes. Thereby, we render deep learning approaches more interpretable. In an application with single-cell gene expression data, we demonstrate the utility of the discussed methods.


Author(s):  
Taku Tsukamoto ◽  
Yuichi Tokuda ◽  
Masakazu Nakano ◽  
Kei Tashiro ◽  
Junya Kuroda

Author(s):  
Brian Richard Healey Bird ◽  
Ken Nally ◽  
Karine Ronan ◽  
Gerard Clarke ◽  
Sylvie Amu ◽  
...  

Immune Checkpoint Inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and Tumour Mutational Burden, none of which are particularly sensitive or specific. Emerging tumour and immune tissue biomarkers such as novel immunohistochemistry scores, tumour, stromal and immune cell gene expression profiling, and liquid biomarkers such as systemic inflammatory markers, kynurenine/tryptophan ratio, circulating immune cells, cytokines and DNA are discussed in this review. We also examine the influence of the faecal microbiome on treatment outcome and its use as a biomarker of response and toxicity.


Author(s):  
Raymond Ching-Bong Wong ◽  
Junjiu Huang ◽  
Dali Li ◽  
Olga Amaral
Keyword(s):  

2021 ◽  
Vol 15 ◽  
Author(s):  
Seulgi Kang ◽  
Soyoung Jun ◽  
Soo Ji Baek ◽  
Heeyoun Park ◽  
Yukio Yamamoto ◽  
...  

The cerebellum has a long history in terms of research on its network structures and motor functions, yet our understanding of them has further advanced in recent years owing to technical developments, such as viral tracers, optogenetic and chemogenetic manipulation, and single cell gene expression analyses. Specifically, it is now widely accepted that the cerebellum is also involved in non-motor functions, such as cognitive and psychological functions, mainly from studies that have clarified neuronal pathways from the cerebellum to other brain regions that are relevant to these functions. The techniques to manipulate specific neuronal pathways were effectively utilized to demonstrate the involvement of the cerebellum and its pathways in specific brain functions, without altering motor activity. In particular, the cerebellar efferent pathways that have recently gained attention are not only monosynaptic connections to other brain regions, including the periaqueductal gray and ventral tegmental area, but also polysynaptic connections to other brain regions, including the non-primary motor cortex and hippocampus. Besides these efferent pathways associated with non-motor functions, recent studies using sophisticated experimental techniques further characterized the historically studied efferent pathways that are primarily associated with motor functions. Nevertheless, to our knowledge, there are no articles that comprehensively describe various cerebellar efferent pathways, although there are many interesting review articles focusing on specific functions or pathways. Here, we summarize the recent findings on neuronal networks projecting from the cerebellum to several brain regions. We also introduce various techniques that have enabled us to advance our understanding of the cerebellar efferent pathways, and further discuss possible directions for future research regarding these efferent pathways and their functions.


2021 ◽  
Author(s):  
Justin S. Antony ◽  
Alberto Daniel-Moreno ◽  
Andrés Lamsfus-Calle ◽  
Janani Raju ◽  
Merve Kaftancioglu ◽  
...  

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