Kidney mRNA-protein expression correlation: What can we learn from the Human Protein Atlas? DOI
Dianne Acoba,

Anna Reznichenko

Published: July 13, 2024

ABSTRACT The Human Protein Atlas (HPA), with more than 10 million immunohistochemical images showing tissue- and cell-specific protein expression levels subcellular localization information, is widely used in kidney research. HPA contains comprehensive data on multi-tissue transcript abundance, allowing for comparisons across tissues. However, while visual intuitive to interpret, immunohistochemistry limited by its semi-quantitative nature. This can lead mismatches measurements different platforms. We performed a comparison of the HPA’s kidney-specific RNA sequencing determine if mRNA abundance are concordant. Our study demonstrates that there discordance between based data. Using an external validatory mass spectrometry dataset, we show 500 proteins undetected robustly measured spectrometry. transcriptome data, other hand, exhibit similar detection as RNA-seq datasets. Such mRNA-protein could be due both biological technical reasons, such transcriptional dynamics, translation rates, half-lives, measurement errors. further complicated heterogeneity tissue itself, which increase cell populations or compartment samples do not match. As such, shedding light relationship provide context our scientific inferences when discuss renal gene quantification.

Language: Английский

Deciphering the Intricacies of Breast Cancer Signaling Network and the Potential of Soy-derived Isoflavones on Cancer Therapeutics DOI Creative Commons
Amir Mahgoub Awadelkareem, Abd Elmoneim O. Elkhalifa, Mohd Adnan

et al.

Pharmacognosy Magazine, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Background Breast cancer remains a significant global health challenge despite the emergence of various drug molecules. However, adverse side effects several drugs and chemotherapy necessitate exploration novel therapeutic strategies. Identifying effective proteins specific to breast is complex, finding potential natural, non-cytotoxic inhibitors presents an even more in this field. Purpose In study, we aimed identify responsible for development cancer, as well explore application isoflavones complementary agents management. Materials Methods Analysis The Cancer Genome Atlas (TCGA) RNA-Seq protein expression data at Human Protein was performed identification proteins. Furthermore, selected were used molecular docking dynamics against isoflavone derivatives. addition, pharmacokinetic activity Results Molecular exhibited most potent binding energy −9.6 kcal/mol CRMP2-genistin closely followed by HER2-daidzin complex with −9.4 kcal/mol. Subsequent simulations showed dynamic behavior, structural integrity, stability, interaction stability HER2 ligand daidzin. According ADMET data, soy satisfy Lipinski, Pfizer, Ghose, GoldenTriangle criteria, indicating drug-like properties. Immunotoxicity projections indicate daidzein has least effects, while silico , cytotoxicity assays minimal overall risk. Glycitin daidzin have lowest levels cytotoxicity. comprehensive profiles, soy-derived can safely complement current therapeutics. Conclusion Computational analysis revealed that these ligands had inhibitory BC-related CRMP2 These could be develop nutraceuticals ensure safe

Language: Английский

Citations

0
Exploring potential key genes and disease mechanisms in Εarly-onset genetic epilepsy via integrated bioinformatics analysis DOI Creative Commons

Vasiliki Boulaki,

Spiros Efthimiopoulos, Nicholas Κ. Moschonas

et al.

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106888 - 106888

Published: April 1, 2025

Epilepsy is a severe common neurological disease affecting all ages. with onset before the age of 5 years, designated early-onset epilepsy (EOE), special importance. According to previous studies, genetic factors contribute significantly pathogenesis EOE that remains unclear and must be explored. So, list 229 well-selected EOE-associated genes expressed in brain was created for investigation molecular mechanisms involved its pathogenesis. Enrichment analysis showed among significant pathways were nicotine addiction, GABAergic synapse, synaptic vesicle cycle, regulation membrane potential, cholinergic dopaminergic morphine addiction. Performing an integrated as well protein-protein interaction network-based approaches use GO, KEGG, ClueGO, cytoHubba 3 network metrics, 12 hub identified, seven which, CDKL5, GABRA1, KCNQ2, KCNQ3, SCN1A, SCN8A STXBP1, identified key (via Venn diagram analysis). These are mostly enriched SNARE interactions vesicular transport, potential exocytosis. Clustering PPI via MCODE functional modules, indicating also other such N-Glycan biosynthesis protein N-linked glycosylation, retrograde endocannabinoid signaling, mTOR signaling aminoacyl-tRNA biosynthesis. Drug-gene number drugs medications EOE, which non-FDA approved azetukalner (under clinical development), indiplon ICA-105665 FDA retigabine, ganaxolone methohexital.

Language: Английский

Citations

0
Syntenin and CD63 Promote Exosome Biogenesis from the Plasma Membrane by Blocking Cargo Endocytosis DOI Creative Commons
Yiwei Ai, Chenxu Guo, Marta Garcia‐Contreras

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 27, 2023

Exosomes are small extracellular vesicles important in health and disease. Syntenin is thought to drive the biogenesis of CD63 exosomes by recruiting Alix ESCRT machinery endosomes, initiating an endosome-mediated pathway exosome biogenesis. Contrary this model, we show here that syntenin drives blocking endocytosis, thereby allowing accumulate at plasma membrane, primary site Consistent with these results, find inhibitors endocytosis induce exosomal secretion CD63, inhibits vesicular cargo proteins, high-level expression itself also endocytosis. These other results indicate bud primarily from their loading into exosomes, expression-dependent regulators biogenesis, even knockout cells.

Language: Английский

Citations

8
A high-resolution spatial map of cilia-associated proteins based on characterization of the human fallopian tube-specific proteome DOI Creative Commons
Cecilia Lindskog,

Feria Hikmet Norradin,

Andreas Digre

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 9, 2024

Abstract Molecular changes in the fallopian tubes (FT) play a crucial role development of cancer and reproductive disorders. Here, we aimed to map key FT proteins on single-cell level utilizing an integrated transcriptomics proteomics approach. Based RNA-seq, 315 genes were identified as elevated FT, out which majority associated with motile cilia function. An in-depth spatial characterization was performed for 130 these other human tissues cilia, localizing different subcellular structures ciliated cells. The specificity cells validated RNA-seq in-situ mass-spectrometry data. Our approach enabled us identify 34 novel cilia-related lacking previous evidence protein level, well several not described context biology. high-resolution aids further disentangling pathways involved infertility diseases linked cilia-specific functions.

Language: Английский

Citations

2
MiR-135b-5p targets ADAM12 to suppress invasion and accelerate trophoblast apoptosis in preeclampsia DOI
Bo Sun,

Taotao Jiang,

Jiayao Yong

et al.

Placenta, Journal Year: 2023, Volume and Issue: 143, P. 69 - 79

Published: Oct. 13, 2023

Language: Английский

Citations

4
Prognostic and immune infiltration implications of SIGLEC9 in SKCM DOI Creative Commons

Yang Peipei,

Yunhui Jiang,

Rong Chen

et al.

Diagnostic Pathology, Journal Year: 2024, Volume and Issue: 19(1)

Published: Aug. 17, 2024

The occurrence and progression of skin cutaneous melanoma (SKCM) is strongly associated with immune cells infiltrating the tumor microenvironment (TME). This study examined expression, prognosis, relevance SIGLEC9 in SKCM using multiple online databases. Analysis GEPIA2 Ualcan databases revealed that highly expressed SKCM, patients high expression had improved overall survival (OS). Furthermore, mutation rate was found to be 5.41%, highest observed. positively correlated macrophages, neutrophils B cells, CD8 + T CD4 dendritic according TIMER. Based on TCGA-SKCM data, we verified closely a good prognosis for patients, including survival, progression-free interval, disease-specific survival. positive could due infiltration into TME. Additionally, our analysis single-cell transcriptome data not only played role normal microenvironment, but also cell subpopulations regulating response tumors. Our findings suggest close association between primarily mediated by its effect microenvironment.

Language: Английский

Citations

1
Unveiling the Molecular Mechanisms of Glioblastoma through an Integrated Network-Based Approach DOI Creative Commons
Ali Kaynar,

Woonghee Kim,

Atakan Burak Ceyhan

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2237 - 2237

Published: Oct. 1, 2024

: Despite current treatments extending the lifespan of Glioblastoma (GBM) patients, average survival time is around 15-18 months, underscoring fatality GBM. This study aims to investigate impact sample heterogeneity on gene expression in GBM, identify key metabolic pathways and modules, explore potential therapeutic targets.

Language: Английский

Citations

1
Mechanism of atorvastatin in treating hepatocellular carcinoma: a study based on network pharmacology, molecular docking, and bioinformatics analysis DOI
Youwen Hu, Yangyang Xiao

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 28, 2024

Language: Английский

Citations

1
K-hyperparameter tuning in high-dimensional genomics using joint optimization of deep differential evolutionary algorithm and unsupervised transfer learning from intelligent GenoUMAP embeddings DOI Creative Commons

Rufus Gikera,

Elizaphan Maina, Shadrack Maina Mambo

et al.

International Journal of Information Technology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 21, 2024

Abstract K-hyperparameter optimization in high-dimensional genomics remains a critical challenge, impacting the quality of clustering. Improved clustering can enhance models for predicting patient outcomes and identifying personalized treatment plans. Subsequently, these enhanced facilitate discovery biomarkers, which be essential early diagnosis, prognosis, response cancer research. Our paper addresses this challenge through four-fold approach. Firstly, we empirically evaluate k- hyperparameter algorithms analysis using correlation based feature selection method stratified fold cross-validation strategy. Secondly, performance best algorithm first step variety dimensionality reduction methods applied reducing search spaces genomics. Building on two, propose novel problem third step, employing joint Deep-Differential-Evolutionary Algorithm Unsupervised Transfer Learning from Intelligent GenoUMAP (Uniform Manifold Approximation Projection). Finally, compare it with existing validate its effectiveness. approach leverages UMAP pre-trained special autoencoder integrates deep-differential-evolutionary tuning k . These choices are empirical results. The balances population size exploration exploitation, helping to find diverse solutions global optimum. learning rate iterations convergence speed, leading stable towards UMAP’s superior performance, demonstrated by short whiskers higher median values comparative analysis, informs choice training new algorithm. enhances balancing reconstruction accuracy, local structure preservation, cluster compactness. comprehensive loss function optimizes quality, promotes diversity, facilitates effective knowledge transfer. This algorithm’s multi-objective makes data analysis. validation three genomic datasets demonstrates scores. Additionally, plots indicate relatively smoother curves an excellent fitness landscape. findings hold significant promise advancing research computational at large.

Language: Английский

Citations

1
Comparison of baseline global gene expression profiles of prostate cancer cell lines LNCaP and DU145 DOI Creative Commons

Khalid Ahmed,

Zhannur Omarova, Alisalman Sheikh

et al.

BMC Research Notes, Journal Year: 2024, Volume and Issue: 17(1)

Published: Dec. 31, 2024

DU145 and LNCaP are classic prostate cancer cell lines. Characterizing their baseline transcriptomics profiles (without any intervention) can offer insights into genetic features oncogenic pathways that should be considered while interpreting findings after various experimental interventions such as exogenous gene transfection or drug treatment.

Language: Английский

Citations

1