GENIPAC: A Genomic Information Portal for Head and Neck Cancer Cell Systems.

Head and neck cancer (HNC)-derived cell lines represent fundamental models for studying the biological mechanisms underlying cancer development and precision therapies. However, mining the genomic information of HNC cells from available databases requires knowledge on bioinformatics and computational skill sets. Here, we developed a user-friendly web resource for exploring, visualizing, and analyzing genomics information of commonly used HNC cell lines. We populated the current version of GENIPAC with 44 HNC cell lines from 3 studies: ORL Series, OPC-22, and H Series. Specifically, the mRNA expressions for all the 3 studies were derived with RNA-seq. The copy number alterations analysis of ORL Series was performed on the Genome Wide Human Cytoscan HD array, while copy number alterations for OPC-22 were derived from whole exome sequencing. Mutations from ORL Series and H Series were derived from RNA-seq information, while OPC-22 was based on whole exome sequencing. All genomic information was preprocessed with customized scripts and underwent data validation and correction through data set validator tools provided by cBioPortal. The clinical and genomic information of 44 HNC cell lines are easily assessable in GENIPAC. The functional utility of GENIPAC was demonstrated with some of the genomic alterations that are commonly reported in HNC, such as TP53, EGFR, CCND1, and PIK3CA. We showed that these genomic alterations as reported in The Cancer Genome Atlas database were recapitulated in the HNC cell lines in GENIPAC. Importantly, genomic alterations within pathways could be simultaneously visualized. We developed GENIPAC to create access to genomic information on HNC cell lines. This cancer omics initiative will help the research community to accelerate better understanding of HNC and the development of new precision therapeutic options for HNC treatment. GENIPAC is freely available at http://genipac.cancerresearch.my/ .

The structural effect of intravitreal Brilliant blue G and Indocyanine green in rats eyes.

PURPOSE: To compare the potential retinal toxicity of two commercially Brilliant blue G dyes (Brilliant Peel and Ocublue Plus) and Indocyanine green (ICG) at usual clinical concentration. METHODS: Brilliant Peel 0.025% (n=9), Ocublue Plus 0.025% (n=9), and ICG 0.05% (n=9) were injected intravitreally into Sprague-Dawley rat left eyes with balanced salt solution injected in the contralateral eyes as control. Evaluation of the effect of the dyes on retinal architecture was done by histological analysis of neurosensory retinal thickness and retinal ganglion cell (RGC) counts 7 days after intravitreal injection. Paired t-test was done to detect the presence of biologically significant thinning in neurosensory retina and five retinal layers for each dye (paired t-tests). One-way ANOVA and Tukey's Honestly Significant Difference test were used to assess whether different dyes caused significant thinning in mean neurosensory retinal thickness and reduction of mean RGC density. RESULTS: Eyes treated with ICG had significantly thinner mean total neurosensory retinal thickness compared with the control eyes (P-value=0.01), followed by those treated with Ocublue Plus (P-value=0.03). Brilliant Peel did not cause significant thinning in any of the five retinal layers (all P-values>0.05). No significant difference in mean thinning of the total retinal thickness was detected between dyes (P-value=0.11). The mean thickness of the photoreceptor outer segment and outer plexiform layers were significantly reduced in ICG-injected eyes when compared with the control eyes (P-value=0.02). No significant difference in mean thinning between the three dyes was detected at all five retinal layers using one-way ANOVA (all P-values>0.35). RGC density was significantly reduced for ICG (P-value=0.01) but only marginally for Ocublue Plus (P-value=0.05). No significant reduction in RGC density was observed for Brilliant Peel (P-value=0.2). CONCLUSION: Intravitreal Brilliant Peel is safe to rats retina. The retinal thinning and reduction in RGC density induced by Ocublue Plus requires further studies to determine the safety profile of this product. Potential retinal toxicity is seen with ICG 0.05%.

Agreement analysis of LENSTAR with other techniques of biometry.

PURPOSE: To assess the agreement of the optical low-coherence reflectometry (OLCR) device LENSTAR LS900 with partial coherence interferometry (PCI) device IOLMaster and applanation and immersion ultrasound biometry. METHODS: We conducted the study at the Ophthalmology Clinic, University of Malaya Medical Center, Malaysia. Phakic eyes of 76 consecutive cataract patients were measured using four different methods: IOLMaster, LENSTAR and A-scan applanation and immersion ultrasound biometry. We assessed the method agreement in the LENSTAR-IOLMaster, LENSTAR-applanation, and LENSTAR-immersion comparisons for axial length (AL) and intraocular lens (IOL) power using Bland-Altman plots. For average K, we compared LENSTAR with IOLMaster and the TOPCON KR-8100 autorefractor-keratometer. SRK/T formula was used to compute IOL power, with emmetropia as the target refractive outcome. RESULTS: For all the variables studied, LENSTAR agreement with IOLMaster is strongest, followed by those with immersion and applanation. For the LENSTAR-IOLMaster comparison, the estimated proportion of differences falling within 0.33 mm from zero AL and within 1D from zero IOL power is 100%. The estimated proportion of differences falling within 0.5 D from zero average K is almost 100% in the LENSTAR-IOLMaster comparison but 88% in the LENSTAR-TOPCON comparison. The proportion of differences falling within 0.10 mm (AL) and within 1D (IOL power) in the LENSTAR-IOLMaster comparison has practically significant discrepancy with that of LENSTAR-applanation and LENSTAR-immersion comparisons. CONCLUSIONS: In phakic eyes of cataract patients, measurements of AL, average K, and IOL power calculated using the SRK/T formula from LENSTAR are biometrically equivalent to those from IOLMaster, but not with those from applanation and immersion ultrasound biometry.

Statistical analysis of binary data generated from multilocus dominant DNA markers.

The use of methodologies such as RAPD and AFLP for studying genetic variation in natural populations is widespread in the ecology community. Because data generated using these methods exhibit dominance, their statistical treatment is less straightforward. Several estimators have been proposed for estimating population genetic parameters, assuming simple random sampling and the Hardy-Weinberg (HW) law. The merits of these estimators remain unclear because no comparative studies of their theoretical properties have been carried out. Furthermore, ascertainment bias has not been explicitly modelled. Here, we present a comparison of a set of candidate estimators of null allele frequency (q), locus-specific heterozygosity (h) and average heterozygosity () in terms of their bias, standard error, and root mean square error (RMSE). For estimating q and h, we show that none of the estimators considered has the least RMSE over the parameter space. Our proposed zero-correction procedure, however, generally leads to estimators with improved RMSE. Assuming a beta model for the distribution of null homozygote proportions, we show how correction for ascertainment bias can be carried out using a linear transform of the sample average of h and the truncated beta-binomial likelihood. Simulation results indicate that the maximum likelihood and empirical Bayes estimator of have negligible bias and similar RMSE. Ascertainment bias in estimators of is most pronounced when the beta distribution is J-shaped and negligible when the latter is inverse J-shaped. The validity of the current findings depends importantly on the HW assumption-a point that we illustrate using data from two published studies.