xGAP: a python based efficient, modular, extensible and fault tolerant genomic analysis pipeline for variant discovery.

MOTIVATION: Since the first human genome was sequenced in 2001, there has been a rapid growth in the number of bioinformatic methods to process and analyze next-generation sequencing (NGS) data for research and clinical studies that aim to identify genetic variants influencing diseases and traits. To achieve this goal, one first needs to call genetic variants from NGS data, which requires multiple computationally intensive analysis steps. Unfortunately, there is a lack of an open-source pipeline that can perform all these steps on NGS data in a manner, which is fully automated, efficient, rapid, scalable, modular, user-friendly and fault tolerant. To address this, we introduce xGAP, an extensible Genome Analysis Pipeline, which implements modified GATK best practice to analyze DNA-seq data with the aforementioned functionalities. RESULTS: xGAP implements massive parallelization of the modified GATK best practice pipeline by splitting a genome into many smaller regions with efficient load-balancing to achieve high scalability. It can process 30× coverage whole-genome sequencing (WGS) data in ∼90 min. In terms of accuracy of discovered variants, xGAP achieves average F1 scores of 99.37% for single nucleotide variants and 99.20% for insertion/deletions across seven benchmark WGS datasets. We achieve highly consistent results across multiple on-premises (SGE & SLURM) high-performance clusters. Compared to the Churchill pipeline, with similar parallelization, xGAP is 20% faster when analyzing 50× coverage WGS on Amazon Web Service. Finally, xGAP is user-friendly and fault tolerant where it can automatically re-initiate failed processes to minimize required user intervention. AVAILABILITY AND IMPLEMENTATION: xGAP is available at https://github.com/Adigorla/xgap. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Local and systemic effects of a silver nitrate coated indwelling pleural catheter in an animal model of pleurodesis.

Purpose/Aim of the study: This study assessed the safety and potential toxicity of a silver nitrate coated indwelling pleural catheter (SNCIPC) designed to create pleurodesis in a large animal model. MATERIALS AND METHODS: Sixteen animals underwent insertion of either a SNCIPC or an uncoated silicone catheter. Half of the animals were sacrificed at day 7 and the others at day 30. Animal weight and assessment of well-being, pleural fluid and blood collection were performed at regular intervals. Pleurodesis was assessed at necropsy and histopathological examination of organs performed. RESULTS: No mortality or significant clinical findings were observed throughout the experiment. SNCIPC treated animals had increased pleural fluid drainage overall (p < 0.001) and specifically on days 1-4. No differences in hemoglobin, white blood cell count or neutrophil counts were detected between groups. No treatment related histological findings were observed in any of the evaluated tissues outside of the treated area. Serum silver levels in SNCIPC catheter treated animals peaked on Day 4 (0.185 µg/mL, 30 day group) then gradually decreased for the remainder of the study period. The highest tissue silver concentrations were noted in the SNCIPC groups in tissues close to the treatment site in addition to the liver (59.8ug/g +/- 8.6 and 73.3ug/g +/- 25). Pleurodesis scores were significantly higher in SNCIPC treated animals for both the 7 day (median 6.5 vs. 1.0, p = 0.029) and 30 day cohorts (median 7.0 vs. 1.5, p = 0.029). CONCLUSIONS: SNCIPC are well tolerated and not associated with any significant signs of toxicity. Silver levels were elevated in local tissues, serum and liver but without evidence of pathological impact. Effective pleurodesis was present by day 7 and more established by day 30. Clinical studies to investigate the safety and efficacy of this device in patients with malignant pleural effusions appear warranted.

Efficacy of a Nanofabricated Electrospun Wound Matrix in Treating Full-thickness Cutaneous Wounds in a Porcine Model.

OBJECTIVE: This study aims to evaluate the comparative performance of a resorbable nanofiber wound matrix (Restrata Wound Matrix; Acera Surgical Inc, St Louis, MO) and a bilayered collagen xenograft (Integra Bilayer Matrix Wound Dressing; Integra, Plainsboro, NJ) in healing critical full-thickness cutaneous wounds in a preclinical porcine model. MATERIALS AND METHODS: Full-thickness cutaneous wounds were created in Yucatan miniature swine and treated with either the nanofiber wound matrix or xenograft. Wound area was measured and inflammation and healing were assessed until euthanasia at day 15 or 30, at which time tissue samples were harvested for histopathology. RESULTS: Wounds treated with the nanofiber wound matrix demonstrated significantly faster wound areal reduction, less inflammation, greater neovascularization, more collagen maturation, and superior quality of healing compared with wounds treated with the xenograft. CONCLUSIONS: The nanofiber wound matrix is an effective wound healing material that may offer a unique alternative in the treatment of challenging refractory wounds.

Comparison of a Fully Synthetic Electrospun Matrix to a Bi-Layered Xenograft in Healing Full Thickness Cutaneous Wounds in a Porcine Model.

A fully synthetic electrospun matrix was compared to a bi-layered xenograft in the healing of full thickness cutaneous wounds in Yucatan miniature swine. Full thickness wounds were created along the dorsum, to which these matrices were applied. The wound area was measured over the course of healing and wound tissue was scored for evidence of inflammation and healing. Animals were sacrificed at Day 15 and Day 30 and tissue samples from the wound site were harvested for histopathological analysis to evaluate inflammation and tissue healing as evidenced by granulation tissue, collagen maturation, vascularization, and epithelialization. Average wound area was significantly smaller for treatment group wounds compared to control group wounds at 15 and 30 days ([7.7 cm2 ± 0.9]/[3.8 cm2 ± 0.8]) and ([2.9 cm2 ± 1.1]/[0.2 cm2 ± 0.0]) (control/treatment) (p = 0.002/p = 0.01). Histopathological analysis of wound sections revealed superior quality of healing with treatment group wounds, as measured by inflammatory response, granulation tissue, and re-epithelialization. A fully synthetic electrospun matrix was associated with faster rates of wound closure characterized by granulation tissue, deposition of mature collagen and vascularization at earlier time points than in wounds treated with a bi-layered xenograft. Treatment with this fully synthetic material may represent a new standard of care by facilitating full-thickness wound closure while eliminating the risks of inflammatory response and disease transmission associated with biologic modalities.