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Generating and evaluating a ranked candidate gene list for potential vertebrate heart field regulators.

ABSTRACT: The vertebrate heart develops from two distinct lineages of cardiomyocytes that arise from the first and second heart fields (FHF and SHF, respectively). The FHF forms the primitive heart tube, while adding cells from the SHF allows elongation at both poles of the tube. Initially seen as an exclusive characteristic of higher vertebrates, recent work has demonstrated the presence of a distinct FHF and SHF in lower vertebrates, including zebrafish. We found that key transcription factors that regulate septation and chamber formation in higher vertebrates, including Tbx5 and Pitx2, influence relative FHF and SHF contributions to the zebrafish heart tube. To identify molecular modulators of heart field migration, we used microarray-based expression profiling following inhibition of tbx5a and pitx2ab in embryonic zebrafish (Mosimann & Panakova, et al, 2015; GSE70750). Here, we describe in more detail the procedure used to process, prioritize, and analyze the expression data for functional enrichment.

SUBMITTER: Musso G

PROVIDER: S-EPMC4664750 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Generating and evaluating a ranked candidate gene list for potential vertebrate heart field regulators.

Musso G G Mosimann C C Panáková D D Burger A A Zhou Y Y Zon L I LI MacRae C A CA

Genomics data 20150916

The vertebrate heart develops from two distinct lineages of cardiomyocytes that arise from the first and second heart fields (FHF and SHF, respectively). The FHF forms the primitive heart tube, while adding cells from the SHF allows elongation at both poles of the tube. Initially seen as an exclusive characteristic of higher vertebrates, recent work has demonstrated the presence of a distinct FHF and SHF in lower vertebrates, including zebrafish. We found that key transcription factors that regu ...[more]

PMID: 26697374

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Project description:ImportanceWith continuing improvements in medical devices and more than a decade since the 2006 United Network for Organ Sharing (UNOS) allocation policy, it is pertinent to assess survival among patients on the heart transplantation waiting list, especially given the recently approved 2018 UNOS allocation policy.ObjectivesTo assess survival outcomes among patients on the heart transplant waiting list during the past 3 decades and to examine the association of ventricular assist devices (VADs) and the 2006 UNOS allocation policy with survival.Design, setting, and participantsA retrospective cross-sectional used the UNOS database to perform an analysis of 95 323 candidates wait-listed for heart transplantation between January 1, 1987, and December 29, 2017. Candidates for all types of combined transplants were excluded (n = 2087). Patients were followed up from the time of listing to death, transplantation, or removal from the list due to clinical improvement. Competing-risk, Kaplan-Meier, and multivariable Cox proportional hazards regression analyses were used.Main outcomes and measuresThe analysis involved an unadjusted and adjusted survival analysis in which the primary outcome was death on the waiting list. Because of changing waiting list preferences and policies during the study period, the intrinsic risk of death for wait-listed candidates was assessed by individually analyzing, comparing, and adjusting for several candidate risk factors.ResultsIn total, 95 323 candidates (72 915 men [76.5%]; mean [SD] age, 51.9 [12.0] years) were studied. In the setting of changes in listing preferences, 1-year survival on the waiting list increased from 34.1% in 1987-1990 to 67.8% in 2011-2017 (difference in proportions, 0.34%; 95% CI, 0.32%-0.36%; P < .001). The 1-year waiting list survival for candidates with VADs increased from 10.2% in 1996-2000 to 70.0% in 2011-2017 (difference in proportions, 0.60%; 95% CI, 0.58%-0.62%; P < .001). Similarly, in the setting of changing mechanical circulatory support indications, the 1-year waiting list survival for patients without VADs increased from 53.9% in 1996-2000 to 66.5% in 2011-2017 (difference in proportions, 0.13%; 95% CI, 0.12%-0.14%; P < .001). In the decade prior to the 2006 UNOS allocation policy, the 1-year waiting list survival was 51.1%, while in the decade after it was 63.9% (difference in proportions, 0.13%; 95% CI, 0.12%-0.14%; P < .001). In adjusted analysis, each time period after 1987-1990 had a marked decrease in waiting list mortality.Conclusions and relevanceThis study found temporally associated increases in heart transplant waiting list survival for all patient groups (with or without VADs, UNOS status 1 and status 2 candidates, and candidates with poor functional status).

Dataset Information

Generating and evaluating a ranked candidate gene list for potential vertebrate heart field regulators.

Publications

Generating and evaluating a ranked candidate gene list for potential vertebrate heart field regulators.

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