Soft windowing application to improve analysis of high-throughput phenotyping data.

MOTIVATION: High-throughput phenomic projects generate complex data from small treatment and large control groups that increase the power of the analyses but introduce variation over time. A method is needed to utlize a set of temporally local controls that maximizes analytic power while minimizing noise from unspecified environmental factors. RESULTS: Here we introduce 'soft windowing', a methodological approach that selects a window of time that includes the most appropriate controls for analysis. Using phenotype data from the International Mouse Phenotyping Consortium (IMPC), adaptive windows were applied such that control data collected proximally to mutants were assigned the maximal weight, while data collected earlier or later had less weight. We applied this method to IMPC data and compared the results with those obtained from a standard non-windowed approach. Validation was performed using a resampling approach in which we demonstrate a 10% reduction of false positives from 2.5 million analyses. We applied the method to our production analysis pipeline that establishes genotype-phenotype associations by comparing mutant versus control data. We report an increase of 30% in significant P-values, as well as linkage to 106 versus 99 disease models via phenotype overlap with the soft-windowed and non-windowed approaches, respectively, from a set of 2082 mutant mouse lines. Our method is generalizable and can benefit large-scale human phenomic projects such as the UK Biobank and the All of Us resources. AVAILABILITY AND IMPLEMENTATION: The method is freely available in the R package SmoothWin, available on CRAN http://CRAN.R-project.org/package=SmoothWin. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hemorragia peripapilar subretinal profunda como complicación asociada a drusen de nervio óptico / Deep subretinal peripapillary bleeding as a complication associated to optic nerve drusen

RESUMEN Los drusen de nervio óptico fueron descritos por primera vez por Liebreich en el año 1868. Otros términos para designar esta entidad incluyen cuerpos hialinos y cuerpos coloides del disco óptico. Tienen una prevalencia de 1 por 500 y el 60 por ciento de los casos se encuentran profundos en la cabeza del nervio óptico. La patogenia primaria de los drusen puede ser una displasia hereditaria del canal óptico del disco óptico y su vasculatura, lo que predispone a la formación de estos. La evolución natural de los drusen es un proceso dinámico que transcurre durante toda la vida. Entre las complicaciones asociadas se presentan defectos de campo visual, pérdida de visión central (rara pero bien documentada), neuropatía óptica isquémica, oclusiones vasculares retinales, pérdidas transitorias de la visión, neovascularización subretinal peripapilar, corioretinopatia serosa central peripapilar y hemorragias pre y peripapilares. Se presenta una paciente de 64 años de edad con antecedente de haber sido operada de desprendimiento de retina del ojo izquierdo, y en el ojo derecho presentaba una hemorragia peripapilar subretinal profunda asociada a drusen(AU)

ABSTRACT Optic nerve drusens were first described by Liebreich in the year 1868. Other terms to designate this condition are optic disc hyaline bodies and colloid bodies. They have a prevalence of 1 per 500 and 60 percent of the cases occur deep in the optic nerve head. The primary pathogenesis of drusens may be an inherited dysplasia of the optic canal of the disc and its vasculature, which leads to their formation. The natural evolution of drusens is a lifelong dynamic process. Associated complications include visual field defects, central vision loss (rare but well documented), ischemic optic neuropathy, retinal vascular occlusion, transient sight loss, peripapillary subretinal neovascularization, central serous peripapillary chorioretinopathy, and pre- and peripapillary bleeding. A case is reported of a 64-year-old female patient with a history of surgery for retinal detachment of the left eye. In the right eye the patient presented deep peripapillary subretinal bleeding associated to drusen(AU)

Lensectomía refractiva en coloboma de iris / Refractive lensectomy for iris coloboma

RESUMEN El coloboma de iris es un defecto congénito, que se describe como un orificio, fisura o hendidura en dicha estructura.​ Esta condición tiene la posibilidad de ser hereditaria o aparecer sin historia familiar previa. Se presenta un caso de un paciente de 51 años de edad con coloboma bilateral de iris asimétrico e hipermetropía, quien acudió a la consulta médica con el deseo de independizarse de su corrección óptica habitual. Se propuso cirugía facorrefractiva de ambos ojos con pupiloplastia del ojo derecho, en el que se obtuvieron resultados visuales satisfactorios después de la intervención quirúrgica(AU)

ABSTRACT The iris coloboma is a congenital defect, present since birth, which is described as a hole, fissure or cleft in the mentioned structure. This condition has the possibility of being inherited or can appear without previous family history. The case is presented of a 51-year-old patient with bilateral asymmetric iris coloboma and farsightedness. The patient went to the doctor's office with the desire to become independent of his usual optical correction. Facorrefractive surgery of both eyes with pupilloplasty of the right eye was proposed, in which satisfactory visual results were obtained after the intervention(AU)

FOXL2 and BPES: mutational hotspots, phenotypic variability, and revision of the genotype-phenotype correlation.

Blepharophimosis syndrome (BPES), an autosomal dominant syndrome in which an eyelid malformation is associated (type I) or not (type II) with premature ovarian failure (POF), has recently been ascribed to mutations in FOXL2, a putative forkhead transcription factor gene. We previously reported 22 FOXL2 mutations and suggested a preliminary genotype-phenotype correlation. Here, we describe 21 new FOXL2 mutations (16 novel ones) through sequencing of open reading frame, 5' untranslated region, putative core promoter, and fluorescence in situ hybridization analysis. Our study shows the existence of two mutational hotspots: 30% of FOXL2 mutations lead to polyalanine (poly-Ala) expansions, and 13% are a novel out-of-frame duplication. In addition, this is the first study to demonstrate intra- and interfamilial phenotypic variability (both BPES types caused by the same mutation). Furthermore, the present study allows a revision of the current genotype-phenotype correlation, since we found exceptions to it. We assume that for predicted proteins with a truncation before the poly-Ala tract, the risk for development of POF is high. For mutations leading to a truncated or extended protein containing an intact forkhead and poly-Ala tract, no predictions are possible, since some of these mutations lead to both types of BPES, even within the same family. Poly-Ala expansions may lead to BPES type II. For missense mutations, no correlations can be made yet. Microdeletions are associated with mental retardation. We conclude that molecular testing may be carefully used as a predictor for POF risk in a limited number of mutations.