Cofactor Genomics: A Sequencing Service Company Emerges from the Technology Development Laboratory

Jump Starting Technologies, Patent Issues, and Translational Medicine Poster SessionCofactor Genomics is based in St. Louis, MO and provides sequencing and analysis services to academic and industry clients. We are a small company committed to changing the service sequencing paradigm by offering our customers front-to-back solutions; experimental design, next-generation sequencing, and advanced analytics for their work. Cofactor Genomics was founded by individuals with one-of-a-kind experience in Next-Generation sequencing technology development. The Cofactor Genomics executive team spent a collective 35 years working in the Technology Development Group at The Genome Center at Washington University in St. Louis, Missouri. From early 2004 to late 2008, their primary responsibilities within the group were to investigate, evaluate and develop both wet-lab and computational applications for emerging Next-Generation sequencing technology platforms. Their experience began with beta testing the 454 Life Sciences (now Roche) GS 20, continued with beta testing the first serial numbered instrument from Solexa (now Illumina), and culminated with beta testing the Applied Biosystems (now Life Technologies) SOLiD instrument. Our individual experiences were unique within the realm of next-generation sequencing technology, thus extremely complimentary for a consolidation and commercialization of skill sets; Matt Hickenbotham became a renowned expert in library construction and Next-Gen instrumentation, Jon Armstrong emerged as an expert in targeted and reduced representation genomic sequencing, and Ryan Richt and Dr. Jarret Glasscock were two of the first individuals in the world to characterize the data generated by these instruments. It is this early-access wet-lab and computational experience with these disruptive sequencing technologies that provided the foundation for operations at Cofactor Genomics. Cofactor Genomics has been in operation for 2 years and has already established a proven track record of capability, versatility, remarkably consistent high quality data generation, and delivering custom data analysis solutions. We constructed 268 different sequencing libraries in our first year spanning nearly every sequencing application and multiple Next-Gen instrument platforms. This feat would be impossible for any firm other than Cofactor to complete in such a short time frame, much to the credit of our highly skilled and talented team. We pooled our talents to form a company offering customers end-to-end sequencing solutions that ultimately allow them to concentrate on what they do best, breakthrough research

Definitive CAD/CAM-Guided Prosthesis for Immediate Loading of Bone-Grafted Maxilla: A Case Report

Background  The reconstruction of a functional occlusion in the presence of severe residual ridge resorption remains a significant challenge for maxillofacial surgeons and prosthodontists. Removable appliances are unsuccessful in severely resorbed cases and the advanced degree of bone loss precludes conventional implant-retained prostehesis. In recent years, bone graft reconstruction of the maxilla and the mandible has been advocated to reverse the debilitating effects of alveolar ridge resorption. Purpose  The surgical objective was the reconstruction of the osseous platform of the jaws, thereby allowing implant-retained definitive prosthetic rehabilitation utilizing the Teeth-in-an-Hour TM concept within 4 months. Materials and Methods  A completely edentulous patient received bone grafts from the posterior iliac crest to augment both the maxillary and mandibular alveolar ridges. The manmandible was augmented using Marx’s “soft issue matrix expansion procedure” and was restored in the conventional manor using an impression and a milled framework. The maxilla underwent “inlay/onlay” bone graft augmentation of the right and left maxilla at the same time as the mandiblular procedure. Implant placement was at 4 months post-bone graft reconstruction. Immediate loading of implants into a bone graft using Nobel Biocare’s Teeth-in-an-Hour TM protocol prelaunch was implemented. This included CT-based implant planning, simultaneous CAD/CAM fabrication of a surgical guide, a CNC-milled framework, flapless surgical placement of the implants, and immediate placement of a pre-fabricated definitive prosthesis. This approach reduced the time necessary for an edentulous patient to transform from severely atrophic alveolar support to implant-retained maxillary and mandibular prosthetic restorations. Immediate loading with an implant retained definitive prosthesis using a bone graft-reconstructed osseous platform was also performed. Conclusion  The Teeth-in-an-Hour TM concept was utilized to restore bone grafted augmentation of the maxilla with immediate loading of a definitive prosthesis within 4 months. The remarkable accuracy of the software, minimally invasive and short surgery and treatment time, uneventful quick recovery with minimal discomfort is a benefit not only to the patient, also to the treating team.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72087/1/j.1708-8208.2006.00018.x.pd

Smart-device Potential for Student Learning.

Smartphones/devices have become the ubiquitous tool of choice for professionals to support their productivity and are increasingly becoming more common on university campuses. Many of the advantages of these devices have the potential to support student learning engagement and provide new opportunities for learning. This paper reports on an academic study conducted over the last two years by two final year students, supported by two academic learning technology researchers, examining the level of student smartphone/device ownership on campus and the extent students are harnessed the use of these devices to support their learning. The research shows that student smartphone/device ownership is increasing; however, how students are using the devices to support their learning appears to narrowing as the year progresses and consequently the students are missing out on the learning opportunities these devices can provide. The paper finally presents an analysis of smartphone/device apps that have the potential to support student learning

The Use of the Decomposition Principle in Making Judgments

One hundred and fifty-one subjects were randomly divided into two groups of roughly equal size. One group was asked to respond to a decomposed version of a problem and the other group was presented with the direct form of the problem. The results provided support for the hypotheses that people can make better judgments when they use the principle of decomposition; and that decomposition is especially valuable for those problems where the subject knows little. The results suggest that accuracy may be improved if the subject provides the data and the computer analyzes it, than if both steps were done implicitly by the subjects

Multiplexed microsphere diagnostic tools in gene expression applications: factors and futures

Microarrays have received significant attention in recent years as scientists have firstly identified factors that can produce reduced confidence in gene expression data obtained on these platforms, and secondly sought to establish laboratory practices and a set of standards by which data are reported with integrity. Microsphere-based assays represent a new generation of diagnostics in this field capable of providing substantial quantitative and qualitative information from gene expression profiling. However, for gene expression profiling, this type of platform is still in the demonstration phase, with issues arising from comparative studies in the literature not yet identified. It is desirable to identify potential parameters that are established as important in controlling the information derived from microsphere-based hybridizations to quantify gene expression. As these evolve, a standard set of parameters will be established that are required to be provided when data are submitted for publication. Here we initiate this process by identifying a number of parameters we have found to be important in microsphere-based assays designed for the quantification of low abundant genes which are variable between studies

Genomic associations with bill length and disease reveal drift and selection across island bird populations

Island species provide excellent models for investigating how selection and drift operate in wild populations, and for determining how these processes act to influence local adaptation and speciation. Here, we examine the role of selection and drift in shaping genomic and phenotypic variation across recently separated populations of Berthelot's pipit (Anthus berthelotii), a passerine bird endemic to three archipelagos in the Atlantic. We first characterized genetic diversity and population structuring that supported previous inferences of a history of recent colonizations and bottlenecks. We then tested for regions of the genome associated with the ecologically important traits of bill length and malaria infection, both of which vary substantially across populations in this species. We identified a SNP associated with variation in bill length among individuals, islands, and archipelagos; patterns of variation at this SNP suggest that both phenotypic and genotypic variation in bill length is largely shaped by founder effects. Malaria was associated with SNPs near/within genes involved in the immune response, but this relationship was not consistent among archipelagos, supporting the view that disease resistance is complex and rapidly evolving. Although we found little evidence for divergent selection at candidate loci for bill length and malaria resistance, genome scan analyses pointed to several genes related to immunity and metabolism as having important roles in divergence and adaptation. Our findings highlight the utility and challenges involved with combining association mapping and population genetic analysis in nonequilibrium populations, to disentangle the effects of drift and selection on shaping genotypes and phenotypes

Real-world outcomes of sipuleucel-T treatment in PROCEED, a prospective registry of men with metastatic castration-resistant prostate cancer.

BackgroundThe large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).MethodsPROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3 years or until death or study withdrawal.ResultsIn 2011-2017, 1976 patients were followed for 46.6 months (median). The median age was 72 years, and the baseline median prostate-specific antigen level was 15.0 ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7 months (95% confidence interval [CI], 28.6-32.2 months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7 months (95% CI, 39.4-46.2 months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.ConclusionsPROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings

A Mobile Augmented Reality Application for Image Guidance of Neurosurgical Interventions

Abstract Image guidance for co mplex surgical procedures is gaining popularity with in operating rooms. Providing the appropriate contextual information to aid in navigation can reduce cognitive load on surgeons, thus reducing surgical error. To date, clinical imp lementations of image guidance have required extensive equip ment, setup and technical expert ise to operate precluding their use when treat ing acute conditions in the intensive care unit. We present an application targeted at mobile p latforms that utilizes augmented reality and image-based tracking in order to add preoperative contextual informat ion to neurosurgical procedures, specifically spatial information. A pilot evaluation was perfo rmed to examine accuracy of the system. Init ial results show increased accuracy for a targeting task with the aid of the visualizat ion

Diversity of woody-host infecting Phytophthora species in public parks and botanic gardens as revealed by metabarcoding, and opportunities for mitigation through best practice

The diversity of Phytophthora species in soils collected from 14 highly disturbed sites in northern Britain, including botanic gardens, arboreta, public parks and other amenity woodland sites, was analysed using a molecular technique known as DNA metabarcoding. This technique enables the identification of multiple species present in a single environmental sample based on a DNA ‘barcode’ unique to each species. The genus Phytophthora was targeted in this study due to its increasing impact on Britain’s forests and woodlands over thelast 20 years. The introduction and spread of new Phytophthora species into Britain has been strongly associated with the movement of traded containerised plants, with a number of Phytophthora outbreaks reported on host trees located in public gardens and parks that had recently undergone planting or landscape regeneration schemes. This study was undertaken to assess the extent to which these highly disturbed sites with extensive planting regimes act as harbours for woody-host infecting Phytophthora species. A total of 23 Phytophthora species, the majority of which are known to be pathogens of woody hosts, were detected across the 14 sites sampled. These included four quarantine-regulated pathogens and four species notpreviously recorded in Britain. Also detected were three as-yet undescribed Phytophthora species and nine oomycete sequences with no clear match to any known genus. There was no effect of geographical location, elevation, underlying soil type, host family or host health status on the Phytophthora assemblages at each site, suggesting that the Phytophthora communities detected are likely to comprise introduced species associated with planting programmes. P. austrocedri and P. pseudosyringae were two of the most abundant Phytophthoraspecies detected, both of which cause serious damage to trees and are regarded as fairly recent introductions to Britain. The practical implications of the findings in terms of mitigating Phytophthora introduction, spread and impact at botanic gardens, arboreta and urban parks are discussed