Bioinformatics Workflows for Genomic Variant Discovery, Interpretation and Prioritization

Next-generation sequencing (NGS) techniques allow high-throughput detection of a vast amount of variations in a cost-efficient manner. However, there still are inconsistencies and debates about how to process and analyse this ‘big data’. To accurately extract clinically relevant information from genomics data, choosing appropriate tools, knowing how to best utilize them and interpreting the results correctly is crucial. This chapter reviews state-of-the-art bioinformatics approaches in clinically relevant genomic variant detection. Best practices of reads-to-variant discovery workflows for germline and somatic short genomic variants are presented along with the most commonly utilized tools for each step. Additionally, methods for detecting structural variations are overviewed. Finally, approaches and current guidelines for clinical interpretation of genomic variants are discussed. As emphasized in this chapter, data processing and variant discovery steps are relatively well-understood. The differences in prioritization algorithms on the other hand can be perplexing, thus creating a bottleneck during interpretation. This review aims to shed light on the pros and cons of these differences to help experts give more informed decisions

Analysis of Correlation between the Seven Important Helicobacter pylori (H. pylori) Virulence Factors and Drug Resistance in Patients with Gastritis

The aim of this study is to evaluate the association between seven important H. pylori virulence factors and antibiotic resistance in patients with gastritis. H. pylori strains isolated from 33 patients with gastritis were examined. Antimicrobial susceptibilities were tested by GenoType® HelicoDR (Hain Life Science, Germany) test kit and RT-PCR. The virulence-factors were determined using conventional PCR. 39% of patients were resistant for clarithromycin and 27% of patients were resistant for fluoroquinolone. 15% of patients were resistant to both clarithromycin and fluoroquinolone. The H. pylori vacA m1/s2 genotype was the most frequent allelic combination. Patients were possessed the vacA s1, m1 (6.1%); s1, m2 (6.1%); s2, m1 (15.1%); and s2, m2 (3.0%) genotypes. 94% of patients with gastritis were positive for H. pylori napA gene. Also, there were no dupA gene-positive gastritis patients. There was no significant correlation between the vacA, cagA, oipA, hpaA, babA, napA, dupA, ureA, ureB virulence genes, clarithromycin, and fluoroquinolone resistance. Herein, we report that the relationship between the H. pylori napA gene and gastritis. Although we found a correlation between H. pylori virulence factor and clinical outcome, there is a need for further studies to enlighten the relation between H. pylori virulence genes and antibiotic resistance

Bimonthly Regimen of High-Dose Leucovorin, Infusional 5-Fluorouracil, Epirubicin and Cisplatin (Modified ECF) as Adjuvant Chemotherapy in Resected Gastric Adenocarcinoma

Background: The administration of the de Gramont regimen in combination with cisplatin and epirubicin (modified ECF) has previously been reported as a treatment for advanced gastric cancer, but here we report this regimen combination in an adjuvant setting for the first time. Methods: Forty-eight patients with curatively resected gastric cancer were treated. Each 2-week cycle consisted of epirubicin (50 mg/m(2)), cisplatin (50 mg/m(2)), 5-fluorouracil (5-FU) IV bolus (400 mg/m(2)) and 5-FU IV (2,400 mg/m(2)) over 46 h plus leucovorin IV (400 mg/m(2)) over 2 h. Postoperative chemoradiotherapy was also administered to the patients when indicated. We retrospectively reviewed the patients who were treated with modified ECF. Results: The median disease-free survival (DFS) was 40.7 months and the 1-, 3- and 5-year DFS rates were 78.5, 55.7 and 44.6%, respectively. The most common grade 3-4 toxicities were hematological and gastrointestinal. Conclusion: A modified ECF regimen may be an effective and convenient treatment with tolerable toxicities for the adjuvant treatment of gastric cancer. It may provide an alternative regimen to the standard ECF when a continuous ambulatory infusion pump is not feasible or not preferred by the patient. Copyright (C) 2012 S. Karger AG, Base

Evaluation of Effect of Garlic Aged Extracts and Vitamin B12 on Noise-Induced Hearing Loss

Objective: This study investigated effects of S-allylmercaptocysteine (SAMC), diallyl disulfide (DADS), and vitamin B12 on inner ear functions and morphology after long-period high-level broadband noise exposure. Materials and Methods: Twenty-four healthy rats were randomly divided into four groups. First group was chosen as the control group. Vitamin B12, SAMC, and DADS were applied to other groups for 4 weeks. On the 14th day, each group was exposed to broadband noise. Auditory brainstem response test was performed before and immediately after noise exposure and repeated on the 2nd and 14th day. Results: Permanent threshold shifts were significantly lower in groups treated with vitamin B12, SAMC, and DADS. Histologically, cochleae of SAMC and DADS groups were found to be better preserved than the cochleae of vitamin B12 and control groups. Conclusion: Physiologically and histologically, SAMC and DADS reduced the long-term effects of noise. However, physiological recovery was not consistent with the morphological findings in vitamin B12 group