Schofieldlynch8495
Cancer cell heterogeneity can manifest genetically and phenotypically. Bioinformatics methods have been used to analyze complex genomics and transcriptomics data, but have not been well-established for analyzing biophysical data of phenotypically heterogeneous tumor cells. find more Here, we take an informatics approach to analyze the biophysical data of MDA-MB-231 cells, a widely used breast cancer cell line, during their spontaneous migration through confined environments. Experimentally, we vary the constriction microchannel geometries (wide channel, short constriction, and long constriction) and apply drug treatments. We find that cells in the short constriction are similar in morphology to the cells in the wide channel. However, their fluorescence profiles are comparable to those in the long constriction. We demonstrate that the cell migratory phenotype is correlated more to mitochondria in a non-confined environment and more to actin in a confined environment. We demonstrate that the cells' migratory phenotypes with the genetic data to relate genetic and phenotypic heterogeneity.
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.Work over the last 40 years have described macrophages as a heterogeneous population that serve as the frontline surveyors of tissue immunity. As a class, macrophages are found in almost every tissue in the body and as distinct populations within discrete microenvironments in any given tissue. During homeostasis, macrophages protect these tissues by clearing invading foreign bodies and/or mounting immune responses. In addition to varying identities regulated by transcriptional programs shaped by their respective environments, macrophage metabolism serves as an additional regulator to temper responses to extracellular stimuli. The area of research known as "immunometabolism" has been established within the last decade, owing to an increase in studies focusing on the crosstalk between altered metabolism and the regulation of cellular immune processes. From this research, macrophages have emerged as a prime focus of immunometabolic studies, although macrophage metabolism and their immune responses have been studied for centuries. During disease, the metabolic profile of the tissue and/or systemic regulators such as endocrine factors, become increasingly dysregulated. Owing to these changes, macrophage responses can become skewed to promote further pathophysiologic changes. For instance, during diabetes, obesity and atherosclerosis, macrophages favor a pro-inflammatory phenotype; whereas in the tumor microenvironment, macrophages elicit an anti-inflammatory response to enhance tumor growth. Herein we have described how macrophages respond to extracellular cues including inflammatory stimuli, nutrient availability and endocrine factors that occur during and to further promote disease progression.
Transcriptome-wide association studies (TWAS) have successfully facilitated the discovery of novel genetic risk loci for many complex traits, including late-onset Alzheimer's disease (AD). However, most existing TWAS methods rely only on gene expression and ignore epigenetic modification (i.e., DNA methylation) and functional regulatory information (i.e., enhancer-promoter interactions), both of which contribute significantly to the genetic basis of AD.
We develop a novel gene-level association testing method that integrates genetically regulated DNA methylation and enhancer-target gene pairs with genome-wide association study (GWAS) summary results. Through simulations, we show that our approach, referred to as the CMO (cross methylome omnibus) test, yielded well controlled type I error rates and achieved much higher statistical power than competing methods under a wide range of scenarios. Furthermore, compared with TWAS, CMO identified an average of 124% more associations when analyzing several brain imaging-related GWAS results. By analyzing to date the largest AD GWAS of 71,880 cases and 383,378 controls, CMO identified six novel loci for AD, which have been ignored by competing methods.
Software https//github.com/ChongWuLab/CMO.
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
As machine learning has become increasingly popular over the last few decades, so too has the number of machine learning interfaces for implementing these models. Whilst many R libraries exist for machine learning, very few offer extended support for survival analysis. This is problematic considering its importance in fields like medicine, bioinformatics, economics, engineering, and more. mlr3proba provides a comprehensive machine learning interface for survival analysis and connects with mlr3's general model tuning and benchmarking facilities to provide a systematic infrastructure for survival modeling and evaluation.
mlr3proba is available under an LGPL-3 license on CRAN and at https//github.com/mlr-org/mlr3proba, with further documentation at https//mlr3book.mlr-org.com/survival.html.
mlr3proba is available under an LGPL-3 license on CRAN and at https//github.com/mlr-org/mlr3proba, with further documentation at https//mlr3book.mlr-org.com/survival.html.Social workers are more than just discharge planners within a hospital setting. In fact, licensed social workers are credentialed to provide therapeutic interventions such as counseling to enhance the discharge planning process. This case study narrative examines prolonged exposure therapy (PE) as an intervention for the discharge of a female veteran psychiatrically hospitalized for one year. The methodology was selected in response to the dearth of research regarding the psychotherapeutic use of PE during the discharge planning process. The veteran in this study experienced both guilt and shame related to her psychiatric hospitalization and was avoidant of her discharge. There is a scarcity of research that examines the impact of distorted beliefs associated with a prolonged hospital stay and the psychotherapeutic approaches within discharge planning in either the medical or psychiatric hospital settings. This article attempts to fill in the gaps in research by specifically reviewing the use of PE to reduce distorted thoughts of guilt and shame because of the fear of returning home posthospitalization.
