Image2_Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis.tif

<p>Lupus nephritis (LN), a complex complication of systemic lupus erythematosus, requires in-depth cellular and molecular analysis for advanced treatment strategies, including mRNA vaccine development. In this study, we analyzed single-cell RNA sequencing data from 24 LN patients and 10 health...

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Main Author: Lisha Mou (151003) (author)
Other Authors: Ying Lu (66401) (author), Zijing Wu (3391769) (author), Zuhui Pu (10931751) (author), Meiying Wang (1309134) (author)
Published: 2024
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_version_ 1852026158879604736
author Lisha Mou (151003)
author2 Ying Lu (66401)
Zijing Wu (3391769)
Zuhui Pu (10931751)
Meiying Wang (1309134)
author2_role author
author
author
author
author_facet Lisha Mou (151003)
Ying Lu (66401)
Zijing Wu (3391769)
Zuhui Pu (10931751)
Meiying Wang (1309134)
author_role author
dc.creator.none.fl_str_mv Lisha Mou (151003)
Ying Lu (66401)
Zijing Wu (3391769)
Zuhui Pu (10931751)
Meiying Wang (1309134)
dc.date.none.fl_str_mv 2024-10-04T04:03:36Z
dc.identifier.none.fl_str_mv 10.3389/fimmu.2024.1381445.s002
dc.relation.none.fl_str_mv https://figshare.com/articles/figure/Image2_Integrating_genomics_and_AI_to_uncover_molecular_targets_for_mRNA_vaccine_development_in_lupus_nephritis_tif/27166881
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Immunology
Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
Autoimmunity
Cellular Immunology
Humoural Immunology and Immunochemistry
Immunogenetics (incl. Genetic Immunology)
Innate Immunity
Transplantation Immunology
Tumour Immunology
Immunology not elsewhere classified
Genetic Immunology
Animal Immunology
Veterinary Immunology
systemic lupus erythematosus
lupus nephritis
genomics
single cell
single-cell RNA sequencing
non-negative matrix factorization (NMF)
machine learning
functional network analysis
dc.title.none.fl_str_mv Image2_Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis.tif
dc.type.none.fl_str_mv Image
Figure
info:eu-repo/semantics/publishedVersion
image
description <p>Lupus nephritis (LN), a complex complication of systemic lupus erythematosus, requires in-depth cellular and molecular analysis for advanced treatment strategies, including mRNA vaccine development. In this study, we analyzed single-cell RNA sequencing data from 24 LN patients and 10 healthy controls, supplemented by bulk RNA-seq data from additional LN patients and controls. By applying non-negative matrix factorization (NMF), we identified four distinct leukocyte meta-programs in LN, highlighting diverse immune functions and potential mRNA vaccine targets. Utilizing 12 machine learning algorithms, we developed 417 predictive models incorporating gene sets linked to key biological pathways, such as MTOR signaling, autophagy, Toll-like receptor, and adaptive immunity pathways. These models were instrumental in identifying potential targets for mRNA vaccine development. Our functional network analysis further revealed intricate gene interactions, providing novel insights into the molecular basis of LN. Additionally, we validated the mRNA expression levels of potential vaccine targets across multiple cohorts and correlated them with clinical parameters such as the glomerular filtration rate (GFR) and pathological stage. This study represents a significant advance in LN research by merging single-cell genomics with the precision of NMF and machine learning, broadening our understanding of LN at the cellular and molecular levels. More importantly, our findings shed light on the development of targeted mRNA vaccines, offering new possibilities for diagnostics and therapeutics for this complex autoimmune disease.</p>
eu_rights_str_mv openAccess
id Manara_7d3ceddcf116e7a70bcd8e7e7e2dbbc5
identifier_str_mv 10.3389/fimmu.2024.1381445.s002
network_acronym_str Manara
network_name_str ManaraRepo
oai_identifier_str oai:figshare.com:article/27166881
publishDate 2024
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY 4.0
spelling Image2_Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis.tifLisha Mou (151003)Ying Lu (66401)Zijing Wu (3391769)Zuhui Pu (10931751)Meiying Wang (1309134)ImmunologyApplied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)AutoimmunityCellular ImmunologyHumoural Immunology and ImmunochemistryImmunogenetics (incl. Genetic Immunology)Innate ImmunityTransplantation ImmunologyTumour ImmunologyImmunology not elsewhere classifiedGenetic ImmunologyAnimal ImmunologyVeterinary Immunologysystemic lupus erythematosuslupus nephritisgenomicssingle cellsingle-cell RNA sequencingnon-negative matrix factorization (NMF)machine learningfunctional network analysis<p>Lupus nephritis (LN), a complex complication of systemic lupus erythematosus, requires in-depth cellular and molecular analysis for advanced treatment strategies, including mRNA vaccine development. In this study, we analyzed single-cell RNA sequencing data from 24 LN patients and 10 healthy controls, supplemented by bulk RNA-seq data from additional LN patients and controls. By applying non-negative matrix factorization (NMF), we identified four distinct leukocyte meta-programs in LN, highlighting diverse immune functions and potential mRNA vaccine targets. Utilizing 12 machine learning algorithms, we developed 417 predictive models incorporating gene sets linked to key biological pathways, such as MTOR signaling, autophagy, Toll-like receptor, and adaptive immunity pathways. These models were instrumental in identifying potential targets for mRNA vaccine development. Our functional network analysis further revealed intricate gene interactions, providing novel insights into the molecular basis of LN. Additionally, we validated the mRNA expression levels of potential vaccine targets across multiple cohorts and correlated them with clinical parameters such as the glomerular filtration rate (GFR) and pathological stage. This study represents a significant advance in LN research by merging single-cell genomics with the precision of NMF and machine learning, broadening our understanding of LN at the cellular and molecular levels. More importantly, our findings shed light on the development of targeted mRNA vaccines, offering new possibilities for diagnostics and therapeutics for this complex autoimmune disease.</p>2024-10-04T04:03:36ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.3389/fimmu.2024.1381445.s002https://figshare.com/articles/figure/Image2_Integrating_genomics_and_AI_to_uncover_molecular_targets_for_mRNA_vaccine_development_in_lupus_nephritis_tif/27166881CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/271668812024-10-04T04:03:36Z
spellingShingle Image2_Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis.tif
Lisha Mou (151003)
Immunology
Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
Autoimmunity
Cellular Immunology
Humoural Immunology and Immunochemistry
Immunogenetics (incl. Genetic Immunology)
Innate Immunity
Transplantation Immunology
Tumour Immunology
Immunology not elsewhere classified
Genetic Immunology
Animal Immunology
Veterinary Immunology
systemic lupus erythematosus
lupus nephritis
genomics
single cell
single-cell RNA sequencing
non-negative matrix factorization (NMF)
machine learning
functional network analysis
status_str publishedVersion
title Image2_Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis.tif
title_full Image2_Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis.tif
title_fullStr Image2_Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis.tif
title_full_unstemmed Image2_Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis.tif
title_short Image2_Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis.tif
title_sort Image2_Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis.tif
topic Immunology
Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
Autoimmunity
Cellular Immunology
Humoural Immunology and Immunochemistry
Immunogenetics (incl. Genetic Immunology)
Innate Immunity
Transplantation Immunology
Tumour Immunology
Immunology not elsewhere classified
Genetic Immunology
Animal Immunology
Veterinary Immunology
systemic lupus erythematosus
lupus nephritis
genomics
single cell
single-cell RNA sequencing
non-negative matrix factorization (NMF)
machine learning
functional network analysis