| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Buschur, Kristina L., et al.
(författare)
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Distinct COPD subtypes in former smokers revealed by gene network perturbation analysis
- 2023
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChronic obstructive pulmonary disease (COPD) varies significantly in symptomatic and physiologic presentation. Identifying disease subtypes from molecular data, collected from easily accessible blood samples, can help stratify patients and guide disease management and treatment.MethodsBlood gene expression measured by RNA-sequencing in the COPDGene Study was analyzed using a network perturbation analysis method. Each COPD sample was compared against a learned reference gene network to determine the part that is deregulated. Gene deregulation values were used to cluster the disease samples.ResultsThe discovery set included 617 former smokers from COPDGene. Four distinct gene network subtypes are identified with significant differences in symptoms, exercise capacity and mortality. These clusters do not necessarily correspond with the levels of lung function impairment and are independently validated in two external cohorts: 769 former smokers from COPDGene and 431 former smokers in the Multi-Ethnic Study of Atherosclerosis (MESA). Additionally, we identify several genes that are significantly deregulated across these subtypes, including DSP and GSTM1, which have been previously associated with COPD through genome-wide association study (GWAS).ConclusionsThe identified subtypes differ in mortality and in their clinical and functional characteristics, underlining the need for multi-dimensional assessment potentially supplemented by selected markers of gene expression. The subtypes were consistent across cohorts and could be used for new patient stratification and disease prognosis.
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| 3. |
- Brown, Brielin C., et al.
(författare)
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Multiset correlation and factor analysis enables exploration of multi-omics data
- 2023
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Ingår i: Cell Genomics. - : Elsevier BV. - 2666-979X. ; 3:8, s. 100359-
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Tidskriftsartikel (refereegranskat)abstract
- Multi-omics datasets are becoming more common, necessitating better integration methods to realize their revolutionary potential. Here, we introduce multi-set correlation and factor analysis (MCFA), an unsupervised integration method tailored to the unique challenges of high-dimensional genomics data that enables fast inference of shared and private factors. We used MCFA to integrate methylation markers, protein expression, RNA expression, and metabolite levels in 614 diverse samples from the Trans-Omics for Precision Medicine/Multi-Ethnic Study of Atherosclerosis multi-omics pilot. Samples cluster strongly by ancestry in the shared space, even in the absence of genetic information, while private spaces frequently capture dataset-specific technical variation. Finally, we integrated genetic data by conducting a genome-wide association study (GWAS) of our inferred factors, observing that several factors are enriched for GWAS hits and trans-expression quantitative trait loci. Two of these factors appear to be related to metabolic disease. Our study provides a foundation and framework for further integrative analysis of ever larger multi-modal genomic datasets.
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| 4. |
- Fitzsimmons-Craft, Ellen E., et al.
(författare)
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Training, supervision, and experience of coaches offering digital guided self-help for mental health concerns
- 2023
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Ingår i: Frontiers in Psychology. - : FRONTIERS MEDIA SA. - 1664-1078. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Accessible, low-cost intervention options are necessary to address the rise in mental health problems among college students. Digital guided self-help, or coached, programs have been developed to provide such services, with many commercially available. As such, there are a large and growing number of individuals coaching these programs. However, an unmet need is to evaluate and assess best practices for training and supervising individuals in these positions. To this end, we describe how we recruited, trained, and supervised coaches as part of a large randomized controlled trial using a widely available digital commercial platform. Coaches were trained to provide digital guided self-help for depression, anxiety, and/or eating disorders for college students. Coaches initially attended three live training sessions over 2-3 weeks, viewed multiple training videos, and read a detailed coaching manual developed by our team. Thereafter, they attended weekly supervision. Following their term, coaches completed an exit survey to assess their supervision and training experiences. A total of 37 of 70 (53%) graduate-level student coaches completed the survey. The experience was reported as very positive (95%). In particular, the majority reported feeling well prepared, more confident, and felt they had developed useful skills for their own practice.
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| 5. |
- Kasela, Silva, et al.
(författare)
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Interaction molecular QTL mapping discovers cellular and environmental modifiers of genetic regulatory effects
- 2024
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 111:1, s. 133-149
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Tidskriftsartikel (refereegranskat)abstract
- Bulk-tissue molecular quantitative trait loci (QTLs) have been the starting point for interpreting disease-associated variants, and context-specific QTLs show particular relevance for disease. Here, we present the results of mapping interaction QTLs (iQTLs) for cell type, age, and other phenotypic variables in multi-omic, longitudinal data from the blood of individuals of diverse ancestries. By modeling the interaction between genotype and estimated cell-type proportions, we demonstrate that cell-type iQTLs could be considered as proxies for cell-type-specific QTL effects, particularly for the most abundant cell type in the tissue. The interpretation of age iQTLs, however, warrants caution because the moderation effect of age on the genotype and molecular phenotype association could be mediated by changes in cell-type composition. Finally, we show that cell-type iQTLs contribute to cell-type-specific enrichment of diseases that, in combination with additional functional data, could guide future functional studies. Overall, this study highlights the use of iQTLs to gain insights into the context specificity of regulatory effects.
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| 6. |
- Taylor, Craig Barr, et al.
(författare)
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Optimizing eating disorder treatment outcomes for individuals identified via screening: An idea worth researching
- 2019
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Ingår i: International Journal of Eating Disorders. - : WILEY. - 0276-3478 .- 1098-108X. ; 52:11, s. 1224-1228
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, online screens have been commonly used to identify individuals who may have eating disorders (EDs), many of whom may be interested in treatment. We describe a new empirical approach that takes advantage of current evidence on empirically supported, effective treatments, while at the same time, uses modern statistical frameworks and experimental designs, data-driven science, and user-centered design methods to study ways to expand the reach of programs, enhance our understanding of what works for whom, and improve outcomes, overall and in subpopulations. The research would focus on individuals with EDs identified through screening and would use continuously monitored data, and interactions of interventions/approaches to optimize reach, uptake, engagement, and outcome. Outcome would be assessed at the population, rather than individual level. The idea worth researching is to determine if an optimization outcome model produces significantly higher rates of clinical improvement at a population level than do current approaches, in which traditional interventions are only offered to the few people who are interested in and able to access them.
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