Identification of sex-associated network patterns in Vaccine-Adverse Event Association Network in VAERS.

BACKGROUND: Vaccines are one of the most important public health successes in last century. Besides effectiveness in reducing the morbidity and mortality from many infectious diseases, a successful vaccine program also requires a rigorous assessment on their safety. Due to the limitations of adverse event (AE) data from clinical trials and post-approval surveillance systems, novel computational approaches are needed to organize, visualize, and analyze such high-dimensional complex data. RESULTS: In this paper, we proposed a network-based approach to investigate the vaccine-AE association network from the Vaccine AE Reporting System (VAERS) data. Statistical summary was calculated using the VAERS raw data and represented in the Resource Description Framework (RDF). The RDF graph was leveraged for network analysis. Specifically, we compared network properties of (1) vaccine - adverse event association network based on reports collected over a 23 year period as well as each year; and (2) sex-specific vaccine-adverse event association network. We observed that (1) network diameter and average path length don't change dramatically over a 23-year period, while the average node degree of these networks changes due to the different number of reports during different periods of time; (2) vaccine - adverse event associations derived from different sexes show sex-associated patterns in sex-specific vaccine-AE association networks. CONCLUSIONS: We have developed a network-based approach to investigate the vaccine-AE association network from the VAERS data. To our knowledge, this is the first time that a network-based approach was used to identify sex-specific association patterns in a spontaneous reporting system database. Due to unique limitations of such passive surveillance systems, our proposed network-based approaches have the potential to summarize and analyze the associations in passive surveillance systems by (1) identifying nodes of importance, irrespective of whether they are disproportionally reported; (2) providing guidance on sex-specific recommendations in personalized vaccinology.

HIV-1 subtype diversity among clinical specimens submitted for routine antiviral drug resistance testing in the United States.

Diversity of human immunodeficiency virus type 1 (HIV-1) has important implications for the diagnosis, treatment, and management of HIV-1-infected individuals. HIV-1 pol sequences from 3895 clinical plasma specimens collected in the United States over a 1-year period and submitted for routine HIV-1 genotypic drug resistance testing were retrospectively analyzed for HIV-1 subtype. Of these 3895 HIV-1 sequences, 207 (5.31%) were determined to be non-B subtypes (including recombinant forms). Among individual states, the percentage of non-B subtypes ranged from 0% (12 states) to 28.57% in South Dakota, with 7 states having percentages of >10%. All 4 states with the highest percentages of non-B subtypes were located within the US West North Central region: Minnesota, 11.82%; Iowa, 15.38%; North Dakota, 25.00%; and South Dakota, 28.57%. Reasons for the unexpectedly wide diversity of HIV-1 subtypes present in multiple states located in the West North Central region of the United States remain to be determined.

HERC2-USP20 axis regulates DNA damage checkpoint through Claspin.

The DNA damage response triggers cell-cycle checkpoints, DNA repair and apoptosis using multiple post-translational modifications as molecular switches. However, how ubiquitination regulates ATR signaling in response to replication stress and single-strand break is still unclear. Here, we identified the deubiquitination enzyme (DUB) USP20 as a pivotal regulator of ATR-related DDR pathway. Through screening a panel of DUBs, we identified USP20 as critical for replication stress response. USP20 is phosphorylated by ATR, resulting in disassociation of the E3 ubiquitin ligase HERC2 from USP20 and USP20 stabilization. USP20 in turn deubiquitinates and stabilizes Claspin and enhances the activation of ATR-Chk1 signaling. These findings reveal USP20 to be a novel regulator of ATR-dependent DNA damage signaling.

Molecular modification of Protein A to improve the elution pH and alkali resistance in affinity chromatography.

Protein A of Staphylococcus aureus has been widely used as an affinity ligand for the purification of immunoglobulin. However, the low elution pH and the sensitivity to alkaline condition restricted the large-scale application of antibody purification. To overcome these disadvantages, the B domain was selected and mutated to Z domain and the recombinant Protein A was reconstructed by linking five Z domains. First, a section of six glycines was inserted into the second loop of Z domain, Z (6G). This increased the elution pH to 4.0-5.0. Then, the site-specific mutagenesis was conducted by replacing the 23rd asparagines to threonine and 30th phenylalanine to alanine, Z (N23T, F30A). These mutations made the recombinant Protein A shown a higher alkaline resistance than the nature Protein A. The work confirmed the modification of Protein A and exhibited the characteristics of recombinant Staphylococcal Protein A for antibody purification.

Linked vaccine adverse event data from VAERS for biomedical data analysis and longitudinal studies.

BACKGROUND: Vaccines have been one of the most successful public health interventions to date. The use of vaccination, however, sometimes comes with possible adverse events. The U.S. FDA/CDC Vaccine Adverse Event Reporting System (VAERS) currently contains more than 200,000 reports for post-vaccination events that occur after the administration of vaccines licensed in the United States. Although the data from the VAERS has been applied to many public health and vaccine safety studies, each individual report does not necessarily indicate a casuality relationship between the vaccine and the reported symptoms. Further statistical analysis and summarization needs to be done before this data can be leveraged. METHODS: This paper introduces our efforts on representing the vaccine-symptom correlations and their corresponding meta-information extracted from the VAERS database using Resource Description Framework (RDF). Numbers of occurrences of vaccine-symptom pairs reported to the VAERS were summarized with corresponding proportional reporting ratios (PRR) calculated. All the data was stored in an RDF file. We then applied network analysis approaches to the RDF data to illustrate a use case of the data for longititual studies. We further dicussed our vision on integrating the data with vaccine information from other sources using RDF linked approach to facilitate more comprehensive analyses. RESULTS: The 1990-2013 data from VAERS has been extracted from the VAERS database. There are 83,148 unique vaccine-symptom pairs with 75 vaccine types and 5,865 different reported symptoms. The yearly and over PRR values for each reported vaccine-symptom pair were calculated. The network properties of networks consisting of significant vaccine-symptom associations (i.e., PRR larger than 1) were then investigated. The results indicated that vaccine-symptom association network is a dense network, with any given node connected to all other nodes through an average of approximately two other nodes and a maximum of five nodes.

Refractory inappropriate sinus tachycardia successfully treated with radiofrequency ablation at the arcuate ridge.

Supraventricular tachycardias similar to sinus rhythm are difficult to evaluate and treat with catheter ablation. In addition to inappropriate sinus tachycardia (IST), curative ablation of atrial tachycardia arising from the crista terminalis is well described. We report the case of a 48-year-old woman with multiple failed ablation attempts for IST successfully ablated on the arcuate ridge. Ultrasound and fluoroscopy-guided mapping and ablation of this specific endocavitary anatomic site may be helpful in certain patients with the diagnosis of IST.

Porous ceramic/agarose composite adsorbents for fast protein liquid chromatography.

Porous ceramic/agarose composite adsorbents were designed and prepared with silica ceramic beads and 4% agarose gel, and then functionalized with a special ligand carboxymethyl. A novel method was introduced to fabricating of the porous silica ceramic beads. The morphology of SEM shows a spherical shape and a porous structure of the ceramic beads. Nitrogen adsorption-desorption analysis gives an average pore size of 287.5 Å, a BET surface area of 29.33 m²/g and a porosity of 41.8%, respectively. Additionally, X-ray diffraction pattern indicates that the amorphous silica has been transformed into two crystal phases of quartz and cristobalite, leading to a porous and rigid skeleton and ensuring the application of the composite beads at high flow velocities. Lysozyme of hen egg-white with the activity of 12,700 U/mg was purified by the composite ion-exchanger in one step and the recovery and purification factor reaches 95.2% and 7.9, respectively.