Clinical phenomapping and outcomes after heart transplantation

Bakir, M.; Jackson, Nicholas; Han, Steve; Bui, Alex A. T.; Chang, En‐Ting; Liem, David A.; Ardehali, A.; Ardehali, Reza; Baas, A.; Press, Marcella Calfon; Cruz, Daniel; Deng, Mario C.; DePasquale, E.C.; Fonarow, Gregg C.; Khuu, T.; Kwon, Murray; Kubak, B.; Nsair, Ali; Phung, Jennifer L.; Reed, Elaine F.; Schaenman, Joanna; Shemin, Richard J.; Zhang, Qiuheng J.; Tseng, Chi Hong; Cadeiras, Martín

doi:10.1016/j.healun.2018.03.006

Cited by 10 publications

(7 citation statements)

References 39 publications

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“…DCAF12 was previously implicated in several immunological processes in humans. In the peripheral blood, the decreased expression of DCAF12 (also known as WDR40A in clinical articles) precedes the onset of post-transplantation organ rejection [98,99]. Additionally, DCAF12 was associated with the development of intestinal Behçet's disease, chronic inflammatory disorder [100].…”

Section: Discussionmentioning

confidence: 99%

CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

Liďák

Baloghová

Kor̆ínek

et al. 2021

IJMS

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Multisubunit cullin-RING ubiquitin ligase 4 (CRL4)-DCAF12 recognizes the C-terminal degron containing acidic amino acid residues. However, its physiological roles and substrates are largely unknown. Purification of CRL4-DCAF12 complexes revealed a wide range of potential substrates, including MOV10, an “ancient” RNA-induced silencing complex (RISC) complex RNA helicase. We show that DCAF12 controls the MOV10 protein level via its C-terminal motif in a proteasome- and CRL-dependent manner. Next, we generated Dcaf12 knockout mice and demonstrated that the DCAF12-mediated degradation of MOV10 is conserved in mice and humans. Detailed analysis of Dcaf12-deficient mice revealed that their testes produce fewer mature sperms, phenotype accompanied by elevated MOV10 and imbalance in meiotic markers SCP3 and γ-H2AX. Additionally, the percentages of splenic CD4+ T and natural killer T (NKT) cell populations were significantly altered. In vitro, activated Dcaf12-deficient T cells displayed inappropriately stabilized MOV10 and increased levels of activated caspases. In summary, we identified MOV10 as a novel substrate of CRL4-DCAF12 and demonstrated the biological relevance of the DCAF12-MOV10 pathway in spermatogenesis and T cell activation.

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Section: Discussionmentioning

confidence: 99%

CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

Liďák

Baloghová

Kor̆ínek

et al. 2021

IJMS

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“…Transcriptome analysis of blood before and after hepatitis B vaccination showed that the level of DCAF12 in nonresponders was significantly upregulated after immunization [ 24 ]. In previous clinical studies, the decrease in DCAF12, also called WDR40A, in peripheral blood preceded organ rejection after organ transplantation [ 25 , 26 ]. DCAF12 is related to the development of intestinal Behçet's disease and chronic inflammatory diseases [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

DCAF12 and HSPA1A May Serve as Potential Diagnostic Biomarkers for Myasthenia Gravis

Nong

Fang

Mao

et al. 2022

BioMed Research International

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Background. Myasthenia gravis (MG) is an autoimmune disease that severely affects the life quality of patients. This study explores the differences in immune cell types between MG and healthy control and the role of immune-related genes in the diagnosis of MG. Methods. The GSE85452 dataset was downloaded from the Gene Expression Omnibus (GEO) database and analyzed using the limma package to determine differentially expressed genes (DEGs) between patients with MG and the control group. Differentially expressed immune cells were analyzed using single-sample gene set enrichment analysis (GSEA), while immune cell-associated modules were identified by weighted gene coexpression network analysis (WGCNA). Then, the expression of the identified hub genes was confirmed by RT-PCR in peripheral blood mononuclear cells (PBMCs) of MG patients. The R package pROC was used to plot the receiver operating characteristics (ROC) curves. Results. The modules related to CD56bright natural killer cells were identified by GSEA and WGCNA. The proportion of CD56bright natural killer cells in the peripheral blood of MG patients is low. The results of RT-PCR showed that the levels of DDB1- and CUL4-associated factor 12 (DCAF12) and heat shock protein family A member 1A (HSPA1A) were significantly decreased in peripheral blood mononuclear cells of MG patients compared with healthy controls. The ROC curve results of DCAF12 and HSPA1A mRNA in MG diagnosis were 0.780 and 0.830, respectively. Conclusions. CD56bright NK cell is lower in MG patients and may affect MG occurrence. DCAF12 and HSPA1A are lowly expressed in PBMCs of MG patients and may serve as the diagnostic biomarkers of MG.

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“…In addition, we performed intervariable clustering for patients. This dual-direction clustering yielded a color map of the results ( Figure 2 ), which visually represents the characteristics of the participants; this technique was recently named as “phenomapping.” 8 , 26 We applied this method to the data of the patient newly starting hemodialysis to assist our visual perception of individual patients. Moreover, the clustering may indicate similarities or redundancies among the clinical variables and provide an optimal method of variable reduction.…”

Section: Discussionmentioning

confidence: 99%

Hierarchical Clustering Analysis for Predicting 1-Year Mortality After Starting Hemodialysis

Komaru

Yoshida

Hamasaki

et al. 2020

Kidney International Reports

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Introduction: For patients with end-stage renal disease (ESRD), due to the heterogeneity of the population, appropriate risk assessment approaches and strategies for further follow-up remain scarce. We aimed to conduct a pilot study for better risk stratification, applying machine learning-based classification to patients with ESRD who newly started maintenance hemodialysis. Methods: We prospectively studied 101 patients with ESRD, who were new to maintenance hemodialysis therapy, between August 2016 and March 2018. Baseline values of variables such as blood and urine tests were obtained before the initiation of hemodialysis. Agglomerative hierarchical clustering was conducted with the collected continuous data. The resulting clusters were followed up for the primary outcome of 1year mortality, as analyzed by the Kaplan-Meier survival curve with log-rank test and the Cox proportional hazard model. Results: The participants were divided into 3 clusters (cluster 1, n ¼ 62; cluster 2, n ¼ 15; cluster 3, n ¼ 24) by hierarchical clustering, using 46 clinical variables. Patients in cluster 3 showed lower systolic blood pressures, and lower serum creatinine and urinary liver-type fatty acid-binding protein levels, before the initiation of hemodialysis. Consequently, cluster 3 was associated with the highest 1-year mortality in the study cohort (P < 0.001), and the difference was significant after adjustment for age and sex (hazard ratio: 10.2; 95% confidence interval: 2.94-46.8, cluster 1 as reference). Conclusion: In this proof-of-concept study, hierarchical clustering discovered a subgroup with a higher 1year mortality at the initiation of hemodialysis. Applying machine learning-derived classification to patients with ESRD may contribute to better risk stratification.

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Clinical phenomapping and outcomes after heart transplantation

Abstract: Time-dependent precision phenotyping is a mechanistically insightful, data-driven approach to characterize patterns of clinical care and identify ways to improve clinical management and outcomes.

Cited by 10 publications

References 39 publications

CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

DCAF12 and HSPA1A May Serve as Potential Diagnostic Biomarkers for Myasthenia Gravis

Hierarchical Clustering Analysis for Predicting 1-Year Mortality After Starting Hemodialysis

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