scRNASequest: an ecosystem of scRNA-seq analysis, visualization, and publishing.

BACKGROUND: Single-cell RNA sequencing is a state-of-the-art technology to understand gene expression in complex tissues. With the growing amount of data being generated, the standardization and automation of data analysis are critical to generating hypotheses and discovering biological insights. RESULTS: Here, we present scRNASequest, a semi-automated single-cell RNA-seq (scRNA-seq) data analysis workflow which allows (1) preprocessing from raw UMI count data, (2) harmonization by one or multiple methods, (3) reference-dataset-based cell type label transfer and embedding projection, (4) multi-sample, multi-condition single-cell level differential gene expression analysis, and (5) seamless integration with cellxgene VIP for visualization and with CellDepot for data hosting and sharing by generating compatible h5ad files. CONCLUSIONS: We developed scRNASequest, an end-to-end pipeline for single-cell RNA-seq data analysis, visualization, and publishing. The source code under MIT open-source license is provided at https://github.com/interactivereport/scRNASequest . We also prepared a bookdown tutorial for the installation and detailed usage of the pipeline: https://interactivereport.github.io/scRNAsequest/tutorial/docs/ . Users have the option to run it on a local computer with a Linux/Unix system including MacOS, or interact with SGE/Slurm schedulers on high-performance computing (HPC) clusters.

CHOmics: A web-based tool for multi-omics data analysis and interactive visualization in CHO cell lines.

Chinese hamster ovary (CHO) cell lines are widely used in industry for biological drug production. During cell culture development, considerable effort is invested to understand the factors that greatly impact cell growth, specific productivity and product qualities of the biotherapeutics. While high-throughput omics approaches have been increasingly utilized to reveal cellular mechanisms associated with cell line phenotypes and guide process optimization, comprehensive omics data analysis and management have been a challenge. Here we developed CHOmics, a web-based tool for integrative analysis of CHO cell line omics data that provides an interactive visualization of omics analysis outputs and efficient data management. CHOmics has a built-in comprehensive pipeline for RNA sequencing data processing and multi-layer statistical modules to explore relevant genes or pathways. Moreover, advanced functionalities were provided to enable users to customize their analysis and visualize the output systematically and interactively. The tool was also designed with the flexibility to accommodate other types of omics data and thereby enabling multi-omics comparison and visualization at both gene and pathway levels. Collectively, CHOmics is an integrative platform for data analysis, visualization and management with expectations to promote the broader use of omics in CHO cell research.

A graph-based recovery and decomposition of Swanson's hypothesis using semantic predications.

OBJECTIVES: This paper presents a methodology for recovering and decomposing Swanson's Raynaud Syndrome-Fish Oil hypothesis semi-automatically. The methodology leverages the semantics of assertions extracted from biomedical literature (called semantic predications) along with structured background knowledge and graph-based algorithms to semi-automatically capture the informative associations originally discovered manually by Swanson. Demonstrating that Swanson's manually intensive techniques can be undertaken semi-automatically, paves the way for fully automatic semantics-based hypothesis generation from scientific literature. METHODS: Semantic predications obtained from biomedical literature allow the construction of labeled directed graphs which contain various associations among concepts from the literature. By aggregating such associations into informative subgraphs, some of the relevant details originally articulated by Swanson have been uncovered. However, by leveraging background knowledge to bridge important knowledge gaps in the literature, a methodology for semi-automatically capturing the detailed associations originally explicated in natural language by Swanson, has been developed. RESULTS: Our methodology not only recovered the three associations commonly recognized as Swanson's hypothesis, but also decomposed them into an additional 16 detailed associations, formulated as chains of semantic predications. Altogether, 14 out of the 19 associations that can be attributed to Swanson were retrieved using our approach. To the best of our knowledge, such an in-depth recovery and decomposition of Swanson's hypothesis has never been attempted. CONCLUSION: In this work therefore, we presented a methodology to semi-automatically recover and decompose Swanson's RS-DFO hypothesis using semantic representations and graph algorithms. Our methodology provides new insights into potential prerequisites for semantics-driven Literature-Based Discovery (LBD). Based on our observations, three critical aspects of LBD include: (1) the need for more expressive representations beyond Swanson's ABC model; (2) an ability to accurately extract semantic information from text; and (3) the semantic integration of scientific literature and structured background knowledge.

Patients initiating peritoneal dialysis started on two icodextrin exchanges daily.

Patients with end-stage renal disease treated with peritoneal dialysis (PD) are often put on standard one size fits all" regimens, despite having varying degrees of residual renal function (RRF). The present study reports our experience with initiation of PD using 2 icodextrin exchanges daily in patients with RRF corresponding to a weekly Kt/Vurea of at least 1.0. Peritoneal and RRF Kt/Vurea were tracked closely, and total Kt/Vurea was maintained between 1.7 and 2.0. One patient developed a rash and was changed to 3 dextrose exchanges daily. All patients were satisfied with their treatment regimen, and no other adverse events or symptoms were reported.

The experience of dialysis therapy among younger adults.

The present study was undertaken to examine the experience of younger dialysis patients with end-stage renal disease (ESRD) care. Structured tape-recorded interviews focusing on perceptions of ESRD care and how that care could be improved were initially conducted with 25 dialysis patients [16 on conventional hemodialysis (HD), 6 on nocturnal in-center HD, 2 on home peritoneal dialysis (PD), and 1 on home HD]. The mean age of the patients was 43.8 +/- 12.2 years, and their mean dialysis duration was 4.6 +/- 3. Oyears. Five important domains were identified from the interviews. Based on those findings, a questionnaire was developed and distributed to 62 ESRD patients (49 on HD, 13 on PD). Several domains were identified that provide insight into how the patients thought their care could be improved. Our results suggest that certain changes in ESRD care might improve the experience of younger dialysis patients.

RNASequest: An End-to-End Reproducible RNAseq Data Analysis and Publishing Framework.

We present RNASequest, a customizable RNA sequencing (RNAseq) analysis, app management, and result publishing framework. Its three-in-one RNAseq data analysis ecosystem consists of (1) a reproducible, configurable expression analysis (EA) module, (2) multi-faceted result presentation in R Shiny, a Bookdown document and an online slide deck, and (3) a centralized data management system. In principle, following up our well-received omics data visualization tool Quickomics, RNASequest automates the differential gene expression analysis step, eases statistical model design by built-in covariates testing module, and further provides a web-based tool, ShinyOne, to manage apps powered by Quickomics and reports generated by running the pipeline on multiple projects in one place. Researchers can experience the functionalities by exploring demo data sets hosted at http://shinyone.bxgenomics.com or following the tutorial, https://interactivereport.github.io/RNASequest/tutorial/docs/introduction.html to set up the framework locally to process private RNAseq datasets. The source code released under MIT open-source license is provided at https://github.com/interactivereport/RNASequest.

Dialysis of the Obese Patient: Meeting Needs for a Growing Epidemic.

Increasing population obesity and associated metabolic consequences has led to increased number of obese patients with chronic kidney disease and end-stage renal disease. While obesity is associated with increased cardiovascular morbidity and mortality, obese dialysis patients present a seeming paradox for survival benefit, given other acute intervening illnesses for those on dialysis with loss of lean body mass overtime. Challenges remain in providing adequate renal replacement options and therapy for this growing segment of obese patients on dialysis which are discussed in this article.

Molecular events in matrix protein metabolism in the aging kidney.

We explored molecular events associated with aging-induced matrix changes in the kidney. C57BL6 mice were studied in youth, middle age, and old age. Albuminuria and serum cystatin C level (an index of glomerular filtration) increased with aging. Renal hypertrophy was evident in middle-aged and old mice and was associated with glomerulomegaly and increase in mesangial fraction occupied by extracellular matrix. Content of collagen types I and III and fibronectin was increased with aging; increment in their mRNA varied with the phase of aging. The content of ZEB1 and ZEB2, collagen type I transcription inhibitors, and their binding to the collagen type Iα2 promoter by ChIP assay also showed age-phase-specific changes. Lack of increase in mRNA and data from polysome assay suggested decreased degradation as a potential mechanism for kidney collagen type I accumulation in the middle-aged mice. These changes occurred with increment in TGFß mRNA and protein and activation of its SMAD3 pathway; SMAD3 binding to the collagen type Iα2 promoter was also increased. TGFß-regulated microRNAs (miRs) exhibited selective regulation. The renal cortical content of miR-21 and miR-200c, but not miR-192, miR-200a, or miR-200b, was increased with aging. Increased miR-21 and miR-200c contents were associated with reduced expression of their targets, Sprouty-1 and ZEB2, respectively. These data show that aging is associated with complex molecular events in the kidney that are already evident in the middle age and progress to old age. Age-phase-specific regulation of matrix protein synthesis occurs and involves matrix protein-specific transcriptional and post-transcriptional mechanisms.

Acute kidney injury predicts outcomes of non-critically ill patients.

OBJECTIVE: To evaluate whether acute kidney injury (AKI), defined as an increase in the serum creatinine level of 0.3 mg/dL or more within 48 hours, predicts outcomes of non-critically ill patients. PATIENTS AND METHODS: Among the adults admitted from June 1, 2005, to June 30, 2007, to the medical wards of a community teaching hospital, 735 patients with AKI and 5089 controls were identified. Demographic and health information, serum creatinine values, and outcomes were abstracted from patients' computerized medical records. Outcomes of patients with AKI were compared with those of controls. In an additional case-control analysis, more detailed clinical information was abstracted from the medical records of 282 pairs of randomly selected, age-matched AKI cases and controls. Conditional multivariate logistic regression analyses were used to adjust for potential confounders of AKI effect on outcomes. RESULTS: Overall, patients with AKI had higher in-hospital mortality (14.8% vs 1.5%; P<.001), longer lengths of stay (median 7.9 vs 3.7 days; P<.001), and higher rates of transfer to critical care areas (28.6% vs 4.3%; P<.001); survivors were more likely to be discharged to an extended care facility (43.1% vs 20.3%; P<.001). Conditional multivariate logistic regression analyses of the 282 pairs of cases and controls showed that patients with AKI were 8 times more likely to die in hospital (odds ratio [OR], 7.9; 95% CI [confidence interval], 2.9-15.3) and were 5 times more likely to have prolonged (>or=7 days) hospital stays (OR, 5.2; 95% CI, 3.5-7.9) and require intensive care (OR, 4.7; 95% CI, 2.7-8.1), after adjustment for age, comorbidities, and other potential confounders. CONCLUSION: In this study, AKI was associated with adverse outcomes in non-critically ill patients.