TY - JOUR
T1 - Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases
AU - Shikhevich, Svetlana
AU - Chadaeva, Irina
AU - Khandaev, Bato
AU - Kozhemyakina, Rimma
AU - Zolotareva, Karina
AU - Kazachek, Anna
AU - Oshchepkov, Dmitry
AU - Bogomolov, Anton
AU - Klimova, Natalya V
AU - Ivanisenko, Vladimir A
AU - Demenkov, Pavel
AU - Mustafin, Zakhar
AU - Markel, Arcady
AU - Savinkova, Ludmila
AU - Kolchanov, Nikolay A
AU - Kozlov, Vladimir
AU - Ponomarenko, Mikhail
N1 - Funding: This study was supported by the Russian Federal Science and Technology Program for the Development of Genetic Technologies.
PY - 2023/2/16
Y1 - 2023/2/16
N2 - Mainstream transcriptome profiling of susceptibility versus resistance to age-related diseases (ARDs) is focused on differentially expressed genes (DEGs) specific to gender, age, and pathogeneses. This approach fits in well with predictive, preventive, personalized, participatory medicine and helps understand how, why, when, and what ARDs one can develop depending on their genetic background. Within this mainstream paradigm, we wanted to find out whether the known ARD-linked DEGs available in PubMed can reveal a molecular marker that will serve the purpose in anyone's any tissue at any time. We sequenced the periaqueductal gray (PAG) transcriptome of tame versus aggressive rats, identified rat-behavior-related DEGs, and compared them with their known homologous animal ARD-linked DEGs. This analysis yielded statistically significant correlations between behavior-related and ARD-susceptibility-related fold changes (log2 values) in the expression of these DEG homologs. We found principal components, PC1 and PC2, corresponding to the half-sum and the half-difference of these log2 values, respectively. With the DEGs linked to ARD susceptibility and ARD resistance in humans used as controls, we verified these principal components. This yielded only one statistically significant common molecular marker for ARDs: an excess of Fcγ receptor IIb suppressing immune cell hyperactivation.
AB - Mainstream transcriptome profiling of susceptibility versus resistance to age-related diseases (ARDs) is focused on differentially expressed genes (DEGs) specific to gender, age, and pathogeneses. This approach fits in well with predictive, preventive, personalized, participatory medicine and helps understand how, why, when, and what ARDs one can develop depending on their genetic background. Within this mainstream paradigm, we wanted to find out whether the known ARD-linked DEGs available in PubMed can reveal a molecular marker that will serve the purpose in anyone's any tissue at any time. We sequenced the periaqueductal gray (PAG) transcriptome of tame versus aggressive rats, identified rat-behavior-related DEGs, and compared them with their known homologous animal ARD-linked DEGs. This analysis yielded statistically significant correlations between behavior-related and ARD-susceptibility-related fold changes (log2 values) in the expression of these DEG homologs. We found principal components, PC1 and PC2, corresponding to the half-sum and the half-difference of these log2 values, respectively. With the DEGs linked to ARD susceptibility and ARD resistance in humans used as controls, we verified these principal components. This yielded only one statistically significant common molecular marker for ARDs: an excess of Fcγ receptor IIb suppressing immune cell hyperactivation.
KW - RNA-Seq
KW - Rattus norvegicus
KW - age-related disease
KW - bootstrap
KW - correlation
KW - differentially expressed gene
KW - human
KW - meta-analysis
KW - molecular marker
KW - principal component
KW - qPCR
UR - https://www.mendeley.com/catalogue/49f96f17-6de8-3390-8844-4b76e40fc91f/
U2 - 10.3390/ijms24043996
DO - 10.3390/ijms24043996
M3 - Article
C2 - 36835409
VL - 24
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 4
M1 - 3996
ER -