| Naslov: | Single-cell transcriptomic and targeted genomic profiling adjusted for inflammation and therapy bias reveal CRTAM and PLCB1 as novel hub genes for anti-tumor necrosis factor alpha therapy response in Crohn’s disease |
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| Avtorji: | ID Gorenjak, Mario (Avtor)
ID Gole, Boris (Avtor)
ID Goričan, Larisa (Avtor)
ID Jezernik, Gregor (Avtor)
ID Prosenc Zmrzljak, Uršula (Avtor)
ID Pernat Drobež, Cvetka (Avtor)
ID Skok, Pavel (Avtor)
ID Potočnik, Uroš (Avtor) |
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| Datoteke: |  RAZ_Gorenjak_Mario_2024.pdf (7,36 MB)
MD5: 4AFD667F7379DDA9424D3CC98E0DB7AA
 https://doi.org/10.3390/pharmaceutics16060835
https://www.mdpi.com/1999-4923/16/6/835
|
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| Jezik: | Angleški jezik |
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| Vrsta gradiva: | Znanstveno delo |
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| Tipologija: | 1.01 - Izvirni znanstveni članek |
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| Organizacija: | MF - Medicinska fakulteta
FKKT - Fakulteta za kemijo in kemijsko tehnologijo
|
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| Opis: | The lack of reliable biomarkers in response to anti-TNFα biologicals hinders
personalized therapy for Crohn’s disease (CD) patients. The motivation behind our study is to shift
the paradigm of anti-TNFα biomarker discovery toward specific immune cell sub-populations using
single-cell RNA sequencing and an innovative approach designed to uncover PBMCs gene expression
signals, which may be masked due to the treatment or ongoing inflammation; Methods: The singlecell
RNA sequencing was performed on PBMC samples from CD patients either naïve to biological
therapy, in remission while on adalimumab, or while on ustekinumab but previously non-responsive
to adalimumab. Sieves for stringent downstream gene selection consisted of gene ontology and
independent cohort genomic profiling. Replication and meta-analyses were performed using publicly
available raw RNA sequencing files of sorted immune cells and an association analysis summary.
Machine learning, Mendelian randomization, and oligogenic risk score methods were deployed to
validate DEGs highly relevant to anti-TNFα therapy response; Results: This study found PLCB1 in
CD4+ T cells and CRTAM in double-negative T cells, which met the stringent statistical thresholds
throughout the analyses. An additional assessment proved causal inference of both genes in response
to anti-TNFα therapy; Conclusions: This study, jointly with an innovative design, uncovered
novel candidate genes in the anti-TNFα response landscape of CD, potentially obscured by therapy
or inflammation. |
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| Ključne besede: | inflammatory bowel diseases, Crohn’s disease, tumor necrosis factor alpha, adalimumab, single-cell gene expression analysis |
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| Status publikacije: | Objavljeno |
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| Verzija publikacije: | Objavljena publikacija |
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| Poslano v recenzijo: | 11.06.2024 |
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| Datum sprejetja članka: | 17.06.2024 |
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| Datum objave: | 19.06.2024 |
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| Založnik: | MDPI |
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| Leto izida: | 2024 |
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| Št. strani: | Str. 1-22 |
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| Številčenje: | Letn. 16, Št. 6, št. članka 835 |
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| PID: | 20.500.12556/DKUM-91297  |
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| UDK: | 616.3 |
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| COBISS.SI-ID: | 199620611 |
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| DOI: | 10.3390/pharmaceutics16060835 |
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| ISSN pri članku: | 1999-4923 |
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| Datum objave v DKUM: | 10.12.2024 |
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| Število ogledov: | 173 |
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| Število prenosov: | 29 |
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| Metapodatki: |    |
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| Področja: | Ostalo
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