Qvistmcmahon7517

Systematic delineation of complex biological systems is an ever-challenging and resource-intensive process. Single-cell transcriptomics allows us to study cell-to-cell variability in complex tissues at an unprecedented resolution. Accurate modeling of gene expression plays a critical role in the statistical determination of tissue-specific gene expression patterns. In the past few years, considerable efforts have been made to identify appropriate parametric models for single-cell expression data. The zero-inflated version of Poisson/negative binomial and log-normal distributions have emerged as the most popular alternatives owing to their ability to accommodate high dropout rates, as commonly observed in single-cell data. Although the majority of the parametric approaches directly model expression estimates, we explore the potential of modeling expression ranks, as robust surrogates for transcript abundance. Here we examined the performance of the discrete generalized beta distribution (DGBD) on real data and devised a Wald-type test for comparing gene expression across two phenotypically divergent groups of single cells. We performed a comprehensive assessment of the proposed method to understand its advantages compared with some of the existing best-practice approaches. We concluded that besides striking a reasonable balance between Type I and Type II errors, ROSeq, the proposed differential expression test, is exceptionally robust to expression noise and scales rapidly with increasing sample size. For wider dissemination and adoption of the method, we created an R package called ROSeq and made it available on the Bioconductor platform.The AP-1 transcription factor (TF) dimer contributes to many biological processes and environmental responses. AP-1 can be composed of many interchangeable subunits. Unambiguously determining the binding locations of these subunits in the human genome is challenging because of variable antibody specificity and affinity. Here, we definitively establish the genome-wide binding patterns of five AP-1 subunits by using CRISPR to introduce a common antibody tag on each subunit. We find limited evidence for strong dimerization preferences between subunits at steady state and find that, under a stimulus, dimerization patterns reflect changes in the transcriptome. Further, our analysis suggests that canonical AP-1 motifs indiscriminately recruit all AP-1 subunits to genomic sites, which we term AP-1 hotspots. We find that AP-1 hotspots are predictive of cell type-specific gene expression and of genomic responses to glucocorticoid signaling (more so than super-enhancers) and are significantly enriched in disease-associated genetic variants. Together, these results support a model where promiscuous binding of many AP-1 subunits to the same genomic location play a key role in regulating cell type-specific gene expression and environmental responses.Systemic lupus erythematosus (SLE) is an incurable autoimmune disease disproportionately affecting women. A major obstacle in finding targeted therapies for SLE is its remarkable heterogeneity in clinical manifestations as well as in the involvement of distinct cell types. To identify cell-specific targets as well as cross-correlation relationships among expression programs of different cell types, we here analyze six major circulating immune cell types from SLE patient blood. selleck compound Our results show that presence of an interferon response signature stratifies patients into two distinct groups (IFNneg vs. IFNpos). Comparing these two groups using differential gene expression and differential gene coexpression analysis, we prioritize a relatively small list of genes from classical monocytes including two known immune modulators TNFSF13B/BAFF (target of belimumab, an approved therapeutic for SLE) and IL1RN (the basis of anakinra, a therapeutic for rheumatoid arthritis). We then develop a multi-cell type extension of the weighted gene coexpression network analysis (WGCNA) framework, termed mWGCNA. Applying mWGCNA to RNA-seq data from six sorted immune cell populations (15 SLE, 10 healthy donors), we identify a coexpression module with interferon-stimulated genes (ISGs) among all cell types and a cross-cell type correlation linking expression of specific T helper cell markers to B cell response as well as to TNFSF13B expression from myeloid cells, all of which in turn correlates with disease severity of IFNpos patients. Our results demonstrate the power of a hypothesis-free and data-driven approach to discover drug targets and to reveal novel cross-correlation across cell types in SLE with implications for other autoimmune diseases.

Transgender, nonbinary and gender-expansive (TGE) people face barriers to abortion care and may consider abortion without clinical supervision.

In 2019, we recruited participants for an online survey about sexual and reproductive health. Eligible participants were TGE people assigned female or intersex at birth, 18 years and older, from across the United States, and recruited through The PRIDE Study or via online and in-person postings.

Of 1694 TGE participants, 76 people (36% of those ever pregnant) reported

trying to end a pregnancy on their own without clinical supervision, and a subset of these (n=40; 19% of those ever pregnant) reported

to do so. Methods fell into four broad categories herbs (n=15, 38%), physical trauma (n=10, 25%), vitamin C (n=8, 20%) and substance use (n=7, 18%). Reasons given for abortion without clinical supervision ranged from perceived efficiency and desire for privacy, to structural issues including a lack of health insurance coverage, legal restrictions, denials of oy choose a safe, effective abortion in either setting.

Abortion became decriminalised in Northern Ireland in October 2019. Until that point there existed no evidence concerning the views of health professionals on decriminalisation or on their willingness to be involved in abortion care. The purpose of this study was to address this lack of evidence, including all categories of health professionals working in obstetrics and gynaecology units in Northern Ireland.

The online survey was targeted at medical, nursing and midwifery staff working in the obstetrics and gynaecology units in each Health and Social Care (HSC) Trust in Northern Ireland. The survey was issued via clinical directors in each Trust using the REDCap platform.

The findings showed widespread support for decriminalisation of abortion up until 24 weeks' gestation (n=169, 54%). The majority of clinicians stated they were willing to provide abortions in certain circumstances (which were undefined) (n=188, 60% medical abortions; n=157, 50% surgical abortions). Despite regional variation, the results show that there are sufficient numbers of clinicians to provide a service within each HSC Trust.