Unlocking immune-mediated disease mechanisms with transcriptomics

Jong, Emma de; Bosco, Anthony

doi:10.1042/bst20200652

Cited by 22 publications

(15 citation statements)

References 57 publications

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“…Genes do not function in isolation, they work together in networks (57), and for this reason gene expression data is not only informative for differences in expression magnitude (e.g. fold changes) but also in network structure (e.g.…”

Section: Identification Of Co-expression Network Underlying the Innat...mentioning

confidence: 99%

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

et al. 2022

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Appropriate innate immune function is essential to limit pathogenesis and severity of severe lower respiratory infections (sLRI) during infancy, a leading cause of hospitalization and risk factor for subsequent asthma in this age group. Employing a systems biology approach to analysis of multi-omic profiles generated from a high-risk cohort (n=50), we found that the intensity of activation of an LPS-induced interferon gene network at birth was predictive of sLRI risk in infancy (AUC=0.724). Connectivity patterns within this network were stronger among susceptible individuals, and a systems biology approach identified IRF1 as a putative master regulator of this response. These findings were specific to the LPS-induced interferon response and were not observed following activation of viral nucleic acid sensing pathways. Comparison of responses at birth versus age 5 demonstrated that LPS-induced interferon responses but not responses triggered by viral nucleic acid sensing pathways may be subject to strong developmental regulation. These data suggest that the risk of sLRI in early life is in part already determined at birth, and additionally that the developmental status of LPS-induced interferon responses may be a key determinant of susceptibility. Our findings provide a rationale for the identification of at-risk infants for early intervention aimed at sLRI prevention and identifies targets which may be relevant for drug development.

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Section: Identification Of Co-expression Network Underlying the Innat...mentioning

confidence: 99%

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

et al. 2022

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“…That allows an unprecedented dissection of transcription within millions of individual cells. Both single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) have exciting applications [65][66][67][68][69][70][71][72][73][74][75][76][77], for instance: (i) discovering and characterizing cell type in health and diseases, such as cancer [13,[78][79][80][81][82][83][84][85][86][87][88][89], with implications in immunology [90], immune-mediated diseases [91], immunotherapy [92][93][94][95][96][97][98][99][100] and drug resistance [101]; (ii) deciphering the roles of such specific cell types in health and disease [102], including mitochondrial heteroplasmy [33]; and (iii) analyzing cell emergence, development and plasticity in tissues and organisms. These studies are also applied to study plant biology [103,104].…”

Section: Functional Genomicsmentioning

confidence: 99%

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

et al. 2021

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Recent developments have revolutionized the study of biomolecules. Among them are molecular markers, amplification and sequencing of nucleic acids. The latter is classified into three generations. The first allows to sequence small DNA fragments. The second one increases throughput, reducing turnaround and pricing, and is therefore more convenient to sequence full genomes and transcriptomes. The third generation is currently pushing technology to its limits, being able to sequence single molecules, without previous amplification, which was previously impossible. Besides, this represents a new revolution, allowing researchers to directly sequence RNA without previous retrotranscription. These technologies are having a significant impact on different areas, such as medicine, agronomy, ecology and biotechnology. Additionally, the study of biomolecules is revealing interesting evolutionary information. That includes deciphering what makes us human, including phenomena like non-coding RNA expansion. All this is redefining the concept of gene and transcript. Basic analyses and applications are now facilitated with new genome editing tools, such as CRISPR. All these developments, in general, and nucleic-acid sequencing, in particular, are opening a new exciting era of biomolecule analyses and applications, including personalized medicine, and diagnosis and prevention of diseases for humans and other animals.

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“…Another advantage of single cell sequencing is to leverage the gene expression profiles of individual cells to infer predicted patterns of intercellular communication with a variety of publicly available analysis toolkits [ 164 ]. Tumours represent a complex and dynamic ecosystem of cells that are frequently transmitting and receiving signals, and this cross-talk can promote the growth of tumour cells and/or propagate the immunosuppressive TME.…”

Section: Development Of Personalised Immunotherapies Guided By Integrated Omicsmentioning

confidence: 99%

Directing the Future Breakthroughs in Immunotherapy: The Importance of a Holistic Approach to the Tumour Microenvironment

Newnes

Armitage

Audsley

et al. 2021

Cancers

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Immunotherapy has revolutionised the treatment of cancers by exploiting the immune system to eliminate tumour cells. Despite the impressive response in a proportion of patients, clinical benefit has been limited thus far. A significant focus to date has been the identification of specific markers associated with response to immunotherapy. Unfortunately, the heterogeneity between patients and cancer types means identifying markers of response to therapy is inherently complex. There is a growing appreciation for the role of the tumour microenvironment (TME) in directing response to immunotherapy. The TME is highly heterogeneous and contains immune, stromal, vascular and tumour cells that all communicate and interact with one another to form solid tumours. This review analyses major cell populations present within the TME with a focus on their diverse and often contradictory roles in cancer and how this informs our understanding of immunotherapy. Furthermore, we discuss the role of integrated omics in providing a comprehensive view of the TME and demonstrate the potential of leveraging multi-omics to decipher the underlying mechanisms of anti-tumour immunity for the development of novel immunotherapeutic strategies.

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Unlocking immune-mediated disease mechanisms with transcriptomics

Cited by 22 publications

References 57 publications

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

Directing the Future Breakthroughs in Immunotherapy: The Importance of a Holistic Approach to the Tumour Microenvironment

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