Pisces: an accurate and versatile variant caller for somatic and germline next-generation sequencing data.

MOTIVATION: Next-generation sequencing technology is transitioning quickly from research labs to clinical settings. The diagnosis and treatment selection for many acquired and autosomal conditions necessitate a method for accurately detecting somatic and germline variants. RESULTS: We have developed Pisces, a rapid, versatile and accurate small-variant calling suite designed for somatic and germline amplicon sequencing applications. Accuracy is achieved by four distinct modules, each incorporating a number of novel algorithmic strategies. AVAILABILITY AND IMPLEMENTATION: Pisces is distributed under an open source license and can be downloaded from https://github.com/Illumina/Pisces. Pisces is available on the BaseSpace™ SequenceHub. It is distributed on Illumina sequencing platforms such as the MiSeq™ and is included in the Praxis™ Extended RAS Panel test which was recently approved by the FDA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Treatment With Topical Deferoxamine Improves Cutaneous Vascularity and Tissue Pliability in an Irradiated Animal Model of Tissue Expander-Based Breast Reconstruction.

PURPOSE: Postmastectomy radiation therapy is an important component of the multimodality approach to later-stage breast cancers. Unfortunately, despite its proven survival benefits, postmastectomy radiation therapy is deleterious to the skin and soft tissue, causing increased complications and worse aesthetic outcomes after breast reconstruction.There is currently no effective pharmaceutical agent to mitigate the soft tissue fibrosis and hypovascularity associated with soft tissue radiation. We hypothesized that a novel topical formulation of deferoxamine (DFX) will result in improved cutaneous vascularity and soft tissue pliability in an animal model of irradiated tissue expander-based breast reconstruction. METHODS: This study consisted of 16 hairless rats divided into 4 equal groups: a control group (expander only), a tissue expanded and irradiated group, a tissue expanded + DFX group, and a tissue expanded/irradiated/DFX group. A novel topical formulation of DFX consisted of reconstituted drug dissolved in agents designed to enhance dermal penetrance. Vessels per high-power field (vHPF) were quantified histologically; micro-computed tomography angiography was used to assess vessel volume fraction (VVF) and vessel length density. RESULTS: Irradiated skin had less vascularity compared with control (3.81 vHPF vs 8.25 vHPF, P = 0.03; 0.79% VVF vs 1.53% VVF, P = 0.06). Treatment of irradiated skin with topical DFX reversed these effects, resulting in vascular findings similar to the control group histologically (7.94 vHPF vs 8.25 HPF, P = 0.985) and via micro-computed tomography angiography (1.05% VVF vs 1.53% VVF, P = 0.272). Similarly, radiation resulted in less volume expansion compared with controls (0.72 vs 0.8 mL, P = 0.04), whereas treatment with topical DFX reversed this effect, allowing for an expansion volume similar to the control group (0.81 vs 0.80 mL, P = 0.999). CONCLUSIONS: In an animal model of irradiated tissue expander-based breast reconstruction, treatment with topical DFX improved the cutaneous vascularity and tissue pliability, resulting in vascular density and final tissue expansion volumes similar to those found in the nonirradiated control group. Topical DFX may be an effective agent for the treatment of soft tissue radiation injury; future studies are indicated to further characterize this novel drug formulation.

A Novel Small-Animal Model of Irradiated, Implant-Based Breast Reconstruction.

BACKGROUND: There is currently a need for a clinically relevant small-animal model for irradiated, implant-based breast reconstruction. Present models are inadequate in terms of suboptimal location of expander placement and mode of radiation delivery, correlating poorly with the human clinical scenario. The authors hypothesized that by delivering fractionated radiation and placing an expander under the scalp of the animal, they would achieve soft-tissue changes histologically analogous to those seen in human irradiated, implant-based breast reconstruction. METHODS: This study consisted of 11 immunocompetent, hairless rats divided into three groups as follows: untreated control (n = 3), tissue-expanded scalps (n = 4), and fractionated irradiation plus tissue expansion of the scalp (n = 4). At the completion of the experiment for each group, skin tissue samples were analyzed histologically for vascularity, epidermal and dermal thickness, and collagen fiber alignment or scar formation. RESULTS: Expanded rat epidermis was significantly thicker and dermis was more vascular than nonexpanded skin. The authors observed a greater degree of collagen fiber alignment in the expanded group compared with nonexpanded skin. The combination of irradiation and expansion resulted in significant dermal thinning, vascular depletion, and increased scar formation compared with expanded skin alone. CONCLUSIONS: The authors describe a novel small-animal model for irradiated, implant-based breast reconstruction where histologic analysis shows structural changes in the skin consistent with known effects of radiation therapy and expansion in human skin. This model represents a significant improvement from previous ones and, as such, holds the potential to be used to test new therapeutic agents to improve clinical outcomes.