De novo identification of expressed cancer somatic mutations from single-cell RNA sequencing data.

Identifying expressed somatic mutations from single-cell RNA sequencing data de novo is challenging but highly valuable. We propose RESA - Recurrently Expressed SNV Analysis, a computational framework to identify expressed somatic mutations from scRNA-seq data. RESA achieves an average precision of 0.77 on three in silico spike-in datasets. In extensive benchmarking against existing methods using 19 datasets, RESA consistently outperforms them. Furthermore, we applied RESA to analyze intratumor mutational heterogeneity in a melanoma drug resistance dataset. By enabling high precision detection of expressed somatic mutations, RESA substantially enhances the reliability of mutational analysis in scRNA-seq. RESA is available at https://github.com/ShenLab-Genomics/RESA .

Temporally integrated transcriptome analysis reveals ASFV pathology and host response dynamics.

African swine fever virus (ASFV) causes a lethal swine hemorrhagic disease and is currently responsible for widespread damage to the pig industry. The pathogenesis of ASFV infection and its interaction with host responses remain poorly understood. In this study, we profiled the temporal viral and host transcriptomes in porcine alveolar macrophages (PAMs) with virulent and attenuated ASFV strains. We identified profound differences in the virus expression programs between SY18 and HuB20, which shed light on the pathogenic functions of several ASFV genes. Through integrated computational analysis and experimental validation, we demonstrated that compared to the virulent SY18 strain, the attenuated HuB20 quickly activates expression of receptors, sensors, regulators, as well as downstream effectors, including cGAS, STAT1/2, IRF9, MX1/2, suggesting rapid induction of a strong antiviral immune response in HuB20. Surprisingly, in addition to the pivotal DNA sensing mechanism mediated by cGAS-STING pathway, infection of the DNA virus ASFV activates genes associated with RNA virus response, with stronger induction by HuB20 infection. Taken together, this study reveals novel insights into the host-virus interaction dynamics, and provides reference for future mechanistic studies of ASFV pathogenicity.

Early perioperative fluid overload is associated with adverse outcomes in deceased donor kidney transplantation.

Kidney transplant recipients are often treated with a large volume of infusion to attain adequate graft perfusion in the early perioperative period. However, it remains unknown whether this fluid therapy is renal responsive or a contributing factor to fluid overload complications. We conducted a retrospective cohort analysis of all recipients who received deceased donor kidney transplantation at an academic teaching hospital from January 2015 to April 2019. Our exposure of interest was early perioperative fluid balance. The primary outcome was graft function at 1, 6, and 12 months after transplantation. The secondary outcome was cardiopulmonary and gastrointestinal complications. Fluid balance was not significantly correlated with graft function in short- or long-term periods. Postoperative complications were higher in recipients with increased fluid balance. Delayed graft function was significantly related to cardiopulmonary and gastrointestinal complications. Cardiovascular disease and high BMI of recipients were strong risk factors for cardiopulmonary complications. Fluid overload was prevalent in the early perioperative period of kidney transplantation. It did not promote renal recovery, but was associated with a high risk of complications. Our findings might be a useful indicator to optimize the perioperative fluid management of kidney transplant recipients.

Kidney transplantation from small pediatric donors may be feasible to those who developed chronic refractory dialysis hypotension: a single-center experience.

BACKGROUND: Chronic refractory dialysis hypotension (CRDH) is a serious issue in dialysis patients waiting for transplants. It leads to fatal clinical outcomes and disqualification from kidney transplantation. Kidney transplantation from pediatric donor to adult patient with lower blood pressure (BP) may be an option. No related study has been reported and we conducted this study to first evaluate the effect of pediatric donor kidney transplantation in CRDH recipients. METHODS: Ten single-kidney transplantations from small pediatric donors after cardiac death in our center between August 2016 and April 2018 were described. Half were CRDH recipients (group A) with intradialytic and interdialytic systolic blood pressure (SBP) below 100 mmHg. Each was paired with no-CRDH recipient (control, group B) from the same donor. The operation method of vascular anastomosis and ureterocystoneostomy was the same as that of adult donors. Clinical characteristics, post-operative treatment and outcomes of all recipients were retrieved. Postoperative BP, graft function and size were compared between two groups. The follow-up time was up to April 2019. RESULTS: There was no acute rejection (AR), graft loss or death in all recipients after transplantation. Their renal function was recovered despite three transient delayed graft function (DGF). There was no significant difference in serum creatinine (SCr) or graft size (P=0.84, 0.94) after transplantation between two groups. For all CRDH recipients, the postoperative SBP was above 100 mmHg (except one, 90-130 mmHg). The BP one year after transplantation was maintained at 110-125/70-85 mmHg. CONCLUSIONS: kidney transplantation from small pediatric donors may be feasible to CRDH recipients and their BP may return to normal after transplantation.