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- Fresard, Laure, et al.
(författare)
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Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
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Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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| 2. |
- Plubell, Deanna L., et al.
(författare)
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Putting Humpty Dumpty Back Together Again : What Does Protein Quantification Mean in Bottom-Up Proteomics? br
- 2022
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 21:4, s. 891-898
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Tidskriftsartikel (refereegranskat)abstract
- Bottom-up proteomics provides peptide measurements and has beeninvaluable for moving proteomics into large-scale analyses. Commonly, a singlequantitative value is reported for each protein-coding gene by aggregating peptidequantities into protein groups following protein inference or parsimony. However, giventhe complexity of both RNA splicing and post-translational protein modification, it isoverly simplistic to assume that all peptides that map to a singular protein-coding genewill demonstrate the same quantitative response. By assuming that all peptides from aprotein-coding sequence are representative of the same protein, we may miss thediscovery of important biological differences. To capture the contributions of existingproteoforms, we need to reconsider the practice of aggregating protein values to a singlequantity per protein-coding gene.
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| 3. |
- Wong, Jean, et al.
(författare)
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Society for perioperative assessment and quality improvement (SPAQI) consensus statement on perioperative smoking cessation
- 2020
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Ingår i: Anesthesia and Analgesia. - 0003-2999. ; 131:3, s. 955-968
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Tidskriftsartikel (refereegranskat)abstract
- Smokers are at increased risk for surgical complications. Despite the known benefits of smoking cessation, many perioperative health care providers do not routinely provide smoking cessation interventions. The variation in delivery of perioperative smoking cessation interventions may be due to limited high-level evidence for whether smoking cessation interventions used in the general population are effective and feasible in the surgical population, as well as the challenges and barriers to implementation of interventions. Yet smoking is a potentially modifiable risk factor for improving short- and long-term patient outcomes. The purpose of the Society for Perioperative Assessment and Quality Improvement (SPAQI) Consensus Statement on Perioperative Smoking Cessation is to present recommendations based on current scientific evidence in surgical patients. These statements address questions regarding the timing and intensity of interventions, roles of perioperative health care providers, and behavioral and pharmacological interventions. Barriers and strategies to overcome challenges surrounding implementation of interventions and future areas of research are identified. These statements are based on the current state of knowledge and its interpretation by a multidisciplinary group of experts at the time of publication.
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