Athanasios Gaitatzes - Academia.edu (original) (raw)

Papers by Athanasios Gaitatzes

Bioinformatics, Dec 21, 2017

Motivation: The ability to produce and analyze whole genome sequencing (WGS) data from samples wi... more Motivation: The ability to produce and analyze whole genome sequencing (WGS) data from samples with structural variations (SV) generated the need to visualize such abnormalities in simplified plots. Conventional two-dimensional representations of WGS data frequently use either circular or linear layouts. There are several diverse advantages regarding both these representations, but their major disadvantage is that they do not use the two-dimensional space very efficiently. We propose a layout, termed the Genome U-Plot, which spreads the chromosomes on a two-dimensional surface and essentially quadruples the spatial resolution. We present the Genome U-Plot for producing clear and intuitive graphs that allows researchers to generate novel insights and hypotheses by visualizing SVs such as deletions, amplifications, and chromoanagenesis events. The main features of the Genome U-Plot are its layered layout, its high spatial resolution and its improved aesthetic qualities. We compare conventional visualization schemas with the Genome U-Plot using visualization metrics such as number of line crossings and crossing angle resolution measures. Based on our metrics, we improve the readability of the resulting graph by at least 2-fold, making apparent important features and making it easy to identify important genomic changes. Results: A whole genome visualization tool with high spatial resolution and improved aesthetic qualities.

The use of immersive virtual reality (VR) systems in museums is a recent trend, as the developmen... more The use of immersive virtual reality (VR) systems in museums is a recent trend, as the development of new interactive technologies has inevitably impacted the more traditional sciences and arts. This is more evident in the case of novel interactive technologies that fascinate the broad public, as has always been the case with virtual reality. The increasing development of VR technologies has matured enough to expand research from the military and scientific visualization realm into more multidisciplinary areas, such as education, art and entertainment. This paper analyzes the interactive virtual environments developed at an institution of informal education and discusses the issues involved in developing immersive interactive virtual archaeology projects for the broad public.

The Journal of Molecular Diagnostics, Nov 1, 2022

BMC Cancer, Jul 13, 2018

Background: HER2 positive (HER2+) breast cancers involve chromosomal structural alterations that ... more Background: HER2 positive (HER2+) breast cancers involve chromosomal structural alterations that act as oncogenic driver events. Methods: We interrogated the genomic structure of 18 clinically-defined HER2+ breast tumors through integrated analysis of whole genome and transcriptome sequencing, coupled with clinical information. Results: ERBB2 overexpression in 15 of these tumors was associated with ERBB2 amplification due to chromoanasynthesis with six of them containing single events and the other nine exhibiting multiple events. Two of the more complex cases had adverse clinical outcomes. Chromosomes 8 was commonly involved in the same chromoanasynthesis with 17. In ten cases where chromosome 8 was involved we observed NRG1 fusions (two cases), NRG1 amplification (one case), FGFR1 amplification and ADAM32 or ADAM5 fusions. ERBB3 over-expression was associated with NRG1 fusions and EGFR and ERBB3 expressions were anti-correlated. Of the remaining three cases, one had a small duplication fully encompassing ERBB2 and was accompanied with a pathogenic mutation. Conclusion: Chromoanasynthesis involving chromosome 17 can lead to ERBB2 amplifications in HER2+ breast cancer. However, additional large genomic alterations contribute to a high level of genomic complexity, generating the hypothesis that worse outcome could be associated with multiple chromoanasynthetic events.

Genes, Chromosomes and Cancer, Jul 30, 2018

Copy number variation (CNV) is a common form of structural variation detected in human genomes, o... more Copy number variation (CNV) is a common form of structural variation detected in human genomes, occurring as both constitutional and somatic events. Cytogenetic techniques like chromosomal microarray (CMA) are widely used in analyzing CNVs. However, CMA techniques cannot resolve the full nature of these structural variations (i.e. the orientation and location of associated breakpoint junctions) and must be combined with other cytogenetic techniques, such as karyotyping or FISH, to do so. This makes the development of a next-generation sequencing (NGS) approach capable of resolving both CNVs and breakpoint junctions desirable. Mate-pair sequencing (MPseq) is a NGS technology designed to find large structural rearrangements across the entire genome. Here we present an algorithm capable of performing copy number analysis from mate-pair sequencing data. The algorithm uses a step-wise procedure involving normalization, segmentation, and classification of the sequencing data. The segmentation technique combines both read depth and discordant mate-pair reads to increase the sensitivity and resolution of CNV calls. The method is particularly suited to MPseq, which is designed to detect breakpoint junctions at high resolution. This allows for the classification step to accurately calculate copy number levels at the relatively low read depth of MPseq. Here we compare results for a series of hematological cancer samples that were tested with CMA and MPseq. We demonstrate comparable sensitivity to the state-of-the-art CMA technology, with the benefit of improved breakpoint resolution. The algorithm provides a powerful analytical tool for the analysis of MPseq results in cancer.

Educational applications often are slow to leverage and use new interaction devices in order to b... more Educational applications often are slow to leverage and use new interaction devices in order to bring new value and allow new forms of gameplay. Following decades of research on how to use 3D simulation and Virtual Environments in education, attention has recently turned to exploring MultiUser Virtual Environments for the educational community. In the following paper we present the results of a pilot simulation battle, created for educational purposes combining the positive aspects of multiuser virtual environments, edutainment VR applications and new Human Computer Interaction (HCI) interfaces. We present the technology used, as well as an evaluation case study of the human-computer interaction results.

Cancer genetics, Feb 1, 2018

Mate-pair sequencing (MPseq), using long-insert, paired-end genomic libraries, is a powerful next... more Mate-pair sequencing (MPseq), using long-insert, paired-end genomic libraries, is a powerful nextgeneration sequencing-based approach for the detection of genomic structural variants. SVAtools is a set of algorithms to detect both chromosomal rearrangements and large (>10 kb) copy number variants (CNVs) in genome-wide MPseq data. SVAtools can also predict gene disruptions and gene fusions, and characterize the genomic structure of complex rearrangements. To illustrate the power of SVAtools' junction detection methods to provide comprehensive molecular karyotypes, MPseq data were compared against a set of samples previously characterized by traditional cytogenetic methods. Karyotype, FISH and chromosomal microarray (CMA), performed for 29 patients in a clinical laboratory setting, collectively revealed 285 breakpoints in 87 rearrangements. The junction detection methods of SVAtools detected 87% of these breakpoints compared to 48%, 42% and 57% for karyotype, FISH and CMA respectively. Breakpoint resolution was also reported to 1 kb or less and additional genomic rearrangement complexities not appreciable by standard cytogenetic techniques were revealed. For example, 63% of CNVs detected by CMA were shown by SVAtools' junction detection to occur secondary to a rearrangement other than a simple deletion or tandem duplication. SVAtools with MPseq provides comprehensive and accurate whole-genome junction detection with improved breakpoint resolution, compared to karyotype, FISH, and CMA combined. This approach to molecular karyotyping offers considerable diagnostic potential for the simultaneous detection of both novel and recurrent genomic rearrangements in hereditary and neoplastic disorders.

Research in virtual reality (VR) is a relatively young field, which has shown considerable growth... more Research in virtual reality (VR) is a relatively young field, which has shown considerable growth in recent years, as the development of new interactive technologies has inevitably impacted the more traditional sciences and arts. This is more evident in the case of novel interactive technologies that fascinate the broad public, as has always been the case with virtual reality. The increasing development of VR technologies has matured enough to expand research from the military and scientific visualization realm into more multidisciplinary areas, such as education, art and entertainment. Consequently, virtual reality interfaces interaction techniques and devices have improved greatly in order to provide more natural and obvious modes of interaction and motivational elements. In spite of various concerns and objections regarding the appropriateness and educational efficacy of virtual reality, there remain compelling reasons for believing that virtual environments warrant serious investigation and can provide strong tools for learning. This paper analyses the direction taken regarding the development of user friendly interfaces and natural modes of interaction for users of varied technical competencies in virtual environments.

Virtual Reality is a novel and innovative technology which allows us, through its applications, t... more Virtual Reality is a novel and innovative technology which allows us, through its applications, to experience abstract concepts and ideas, visit spaces that are unreachable or no longer exist, and examine e objects from diverse and unique points of view. Virtual archaeology refers to the use of 3D computer models of ancient buildings and artifacts visualized through immersive technologies. In this paper we explore issues involved in creating immersive cultural heritage projects enhancing our perspective and understanding of the environments in which our ancestors lived and worked.

Supplemental Figure 2 presents genome coverage plots for four example cases illustrating complex ... more Supplemental Figure 2 presents genome coverage plots for four example cases illustrating complex rearrangements between chromosomes (A-D) plus a schematic of the complex TMPRSS2-ERG rearrangement in PR084. Supplemental Figure 3 illustrates the number of breakpoints from genomic rearrangements hitting chromosome 21q. Supplemental Figure 4 illustrates survival analysis from data from Fraser et al 2017 comparing non-indolent prostate cancers with TMPRSS2-ERG fusions with interstitial deletion or retention.

Clinicopath data and case event summary

Supplemental Figure 1. Coverage across 21q Coverage across chromosome 21q for each case in this s... more Supplemental Figure 1. Coverage across 21q Coverage across chromosome 21q for each case in this study. Yellow horizontal line represents 2 copy level across whole genome. Grey line indicates predicted normal 2 copy level coverage across 21q. Red and Blue represent predicted copy number loss or gain regions respectively. Magenta lines indicate rearrangement breakpoints; arcs = intra 21q, upward lines = inter chromosomal translocations. Location of ERG and TMPRSS2 genes indicated by light grey vertical lines. ERG TMPRSS2

Coverage level for each gene located between TMPRSS2 and ERG.

TMPRSS2-ERG gene fusions occur in over 50% of prostate cancers, but their impact on clinical outc... more TMPRSS2-ERG gene fusions occur in over 50% of prostate cancers, but their impact on clinical outcomes is not well understood. Retention of interstitial genes between TMPRSS2 and ERG has been reported to influence tumor progression in an animal model. In this study, we analyzed the status of TMPRSS2-ERG fusion genes and interstitial genes in tumors from a large cohort of men treated surgically for prostate cancer, associating alterations with biochemical progression. Through whole-genome mate pair sequencing, we mapped and classified rearrangements driving ETS family gene fusions in 133 cases of very low-, low-, intermediate-, and high-risk prostate cancer from radical prostatectomy specimens. TMPRSS2-ERG gene fusions were observed in 44% of cases, and over 90% of these fusions occurred in ERG exons 3 or 4. ERG fusions retaining interstitial sequences occurred more frequently in very low-risk tumors. These tumors also frequently displayed ERG gene fusions involving alternative 5′-par...

Mayo Clinic Proceedings, 2019

Objective: To test the hypothesis that chromosomal rearrangements (CRs) can distinguish low risk ... more Objective: To test the hypothesis that chromosomal rearrangements (CRs) can distinguish low risk of progression (LRP) from intermediate and high risk of progression (IHRP) to prostate cancer (PCa) and if these CRs have the potential to identify men with LRP on needle biopsy that harbor IHRP PCa in the prostate gland. Patients and Methods: Mate pair sequencing of amplified DNA from pure populations of Gleason patterns in 154 frozen specimens from 126 patients obtained between August 14, 2001, and July 15, 2011, was used to detect CRs including abnormal junctions and copy number variations. Potential CR biomarkers with higher incidence in IHRP than in LRP to cancer and having significance in PCa biology were identified. Independent validation was performed by fluorescence in situ hybridization in 152 specimens from 124 patients obtained between February 12, 2002, and July 12, 2008. Results: The number of abnormal junctions did not distinguish LRP from IHRP. Loci corresponding to genes implicated in PCa were more frequently altered in IHRP. Integrated analysis of copy number variations and microarray data yielded 6 potential markers that were more frequently detected in Gleason pattern 3 of a Gleason score 7 of PCa than in Gleason pattern 3 of a Gleason score 6 PCa. Five of those were cross-validated in an independent sample set with statistically significant areas under the receiver operating characteristic curves (AUCs) (P.01). Probes detecting deletions in PTEN and CHD1 had AUCs of 0.87 (95% CI, 0.77-0.97) and 0.73 (95% CI, 0.60-0.86), respectively, and probes detecting gains in ASAP1, MYC, and HDAC9 had AUCs of 0.71 (95% CI, 0.59-0.84), 0.82 (95% CI, 0.71-0.93), and 0.77 (95% CI, 0.66-0.89), respectively (for expansion of gene symbols, use search tool at www.genenames.org). Conclusion: Copy number variations in regions encompassing important PCa genes were predictive of cancer significance and have the potential to identify men with LRP PCa by needle biopsy who have IHRP PCa in their prostate gland.

Václav Skala - UNION Agency, 2010

We present a novel GPU-based method for accelerating the visibility function computation of the l... more We present a novel GPU-based method for accelerating the visibility function computation of the lighting equation in dynamic scenes composed of rigid objects. The method pre-computes, for each object in the scene, the visibility and normal information, as seen from the environment, onto the bounding sphere surrounding the object and encodes it into maps. The visibility function is encoded by a four-dimensional visibility field that describes the distance of the object in each direction for all positional samples on a sphere around the object. In addition, the normal vectors of each object are computed and stored in corresponding fields for the same positional samples for use in the computation of reflection in ray-tracing. Thus we are able to speed up the calculation of most algorithms that trace rays to real-time frame rates. The pre-computation time of our method is relatively small. The space requirements amount to 1 byte per ray direction for the computation of ambient occlusion and soft shadows and 4 bytes per ray direction for the computation of reflection in ray-tracing. We present the acceleration results of our method and show its application to two different intersection intensive domains, ambient occlusion computation and stochastic ray tracing on the GPU.

SUMMARY Research in virtual reality (VR) is a relatively young field, which has shown considerabl... more SUMMARY Research in virtual reality (VR) is a relatively young field, which has shown considerable growth in recent years, as the development of new interactive technologies has inevitably impacted the more traditional sciences and arts. This is more evident in the case of novel interactive technologies that fascinate the broad public, as has always been the case with virtual reality. The increasing development of VR technologies has matured enough to expand research from the military and scientific visualization realm into more multidisciplinary areas, such as education, art and entertainment. Consequently, virtual reality interfaces interaction techniques and devices have improved greatly in order to provide more natural and obvious modes of interaction and motivational elements. In spite of various concerns and objections regarding the appropriateness and educational efficacy of virtual reality, there remain compelling reasons for believing that virtual environments warrant serio...

The volumes in the order that they appear are the occupancy volume, the albedo volume, the normal... more The volumes in the order that they appear are the occupancy volume, the albedo volume, the normals volume and the lighting volume and the 2nd order spherical harmonics volume of the direct illumination (R component). An increasing number of rendering and geometry processing algorithms relies on volume data to calculate any-thing from effects like smoke/fluid simulations, visibility information or global illumination effects. We present two real-time and simple-to-implement novel surface voxelization algorithms and a volume data caching structure, the Volume Buffer, which encapsulates functionality, storage and access similar to a frame buffer object, but for three-dimensional scalar data. The Volume Buffer can rasterize primitives in 3d space and accumulate up to 1024 bits of arbitrary data per voxel, as required by the specific application. The strength of our methods is the simplicity of the implementation resulting in fast computation times and very easy integration with existing...