Document Type

Conference Paper

Disciplines

3. MEDICAL AND HEALTH SCIENCES, Radiology, nuclear medicine and medical imaging

Publication Details

https://spie.org/Publications/Proceedings/Paper/10.1117/12.2670747

Proc. SPIE 12627, Translational Biophotonics: Diagnostics and Therapeutics III, 1262708 (30 August 2023);

doi: 10.1117/12.2670747

Abstract

MicroRNAs are small ~22 nucleotide RNA sequences that are guided to the 3’ untranslated region (UTR) of protein-coding target mRNA sequences. One particular microRNA, miR155, plays a remarkable role in the immune system, where it is essential for mounting appropriate immune responses. However, its dysregulation has been identified in multiple inflammatory disorders such as Multiple Sclerosis (MS), arthritis, psoriasis and colitis. More specifically, miR-155 has been found to be elevated in the serum and brain lesions of MS patients. Importantly, therapeutic inhibition of miR-155 can inhibit progression of the MS disease model. One of us has identified that macrophages are major contributor to miR-155 elevation in the MS disease model, whilst its inhibition specifically in macrophages can limit the disease. Here macrophages were isolated from the femur and tibia of wild-type (WT) mice and mice with a knock-out (KO) of the gene regulating miR-155 production, and were cultured in-vitro and stimulated with lipopolysaccharide (LPS) to simulate an immune response. Cells were then prepared for spectral analysis by FTIR imaging with a Perkin-Elmer Spotlight 400 imaging microscope. After pre-processing the dimensionality of spectra were reduced using principal components analysis, kernel-PCA and universal manifold application and projection (UMAP) and classified using a support vector machine algorithm, delivering a classification performance approaching F1~0.89. Spectral features differentiating WT and KO classes were observed across the fingerprint region with no single spectral marker being the sole source of differentiation of the downstream molecular events. This study exemplifies the challenge in spectral discrimination of the complexity of molecular events in ex-vivo models of immune dysregulation.

DOI

https://doi.org/10.1117/12.2670747

Funder

This work was financially supported in part by Science Foundation Ireland Grant Agreements #13/RC/2106-P2 and 19/FFP/6772 at the ADAPT SFI Research Centre at TU Dublin. The ADAPT SFI Centre for Digital Media Technology is funded by Science Foundation Ireland through the SFI Research Centres Programme and is co-funded under the European Regional Development Fund (ERDF).

Creative Commons License

Creative Commons Attribution-Share Alike 4.0 International License
This work is licensed under a Creative Commons Attribution-Share Alike 4.0 International License.

Download


Share

COinS