Skim-sequencing based genotyping reveals genetic divergence of the wild and domesticated population of black tiger shrimp (<i>Penaeus monodon</i>) in the Indo-Pacific region

The domestication of a wild-caught aquatic animal is an evolutionary process, which results in genetic discrimination at the genomic level in response to strong artificial selection. Although black tiger shrimp (Penaeus monodon) is one of the most commercially important aquaculture species, a systematic assessment of genetic divergence and structure of wild-caught and domesticated broodstock populations of the species is yet to be documented. Therefore, we used skim sequencing (SkimSeq) based genotyping approach to investigate the genetic structure of 50 broodstock individuals of P. monodon species, collected from five sampling sites (n = 10 in each site) across their distribution in Indo-Pacific regions. The wild-caught P. monodon broodstock population were collected from Malaysia (MS) and Japan (MJ), while domesticated broodstock populations were collected from Madagascar (MMD), Hawaii, HI, USA (MMO), and Thailand (MT). After various filtering process, a total of 194,259 single nucleotide polymorphism (SNP) loci were identified, in which 4983 SNP loci were identified as putatively adaptive by the pcadapt approach. In both datasets, pairwise FST estimates high genetic divergence between wild and domesticated broodstock populations. Consistently, different spatial clustering analyses in both datasets categorized divergent genetic structure into two clusters: (1) wild-caught populations (MS and MJ), and (2) domesticated populations (MMD, MMO and MT). Among 4983 putatively adaptive SNP loci, only 50 loci were observed to be in the coding region. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that non-synonymous mutated genes might be associated with the energy production, metabolic functions, respiration regulation and developmental rates, which likely act to promote adaptation to the strong artificial selection during the domestication process. This study has demonstrated the applicability of SkimSeq in a highly duplicated genome of P. monodon specifically, across a range of genetic backgrounds and geographical distributions, and would be useful for future genetic improvement program of this species in aquaculture

Intravenous abatacept in Japanese patients with polyarticular-course juvenile idiopathic arthritis : results from a phase III open-label study

Background: To investigate efficacy and safety of intravenous abatacept in Japanese patients with active polyarticular-course juvenile idiopathic arthritis (pJIA). Methods: In this phase III, open-label, multicenter, single-arm study, patients with pJIA aged 4–17 years who failed ≥1 biologic or methotrexate received weight-tiered ( 100 kg: 1000 mg) intravenous abatacept at Weeks 0, 2, 4, and every 4 weeks thereafter. The study comprised a short-term period (16 weeks) and ongoing long-term period. Primary endpoint: Week 16 JIA-American College of Rheumatology criteria 30 (JIA-ACR30) response rate. Secondary endpoints/outcomes included Week 16 JIA-ACR50/70/90 response and inactive disease rates, Childhood Health Assessment Questionnaire-Disability Index (CHAQ-DI), pharmacokinetics, safety, and immunogenicity. Proportions of patients achieving Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein (JADAS27-CRP) remission (score < 1) and minimal disease activity (MDA; score < 3.8), were among exploratory endpoints. Results: All 20 patients who received study medication completed the short-term period. During the long-term period, two patients discontinued due to insufficient efficacy or patient decision. Median age and disease duration at baseline were 10.5 and 0.75 years, respectively. Week 16 JIA-ACR30 response rate (primary endpoint) was 90.0% (18/20). JIA-ACR50/70/90 response and inactive disease rates at Week 16 were 75.0% (15/20), 70.0% (14/20), 35.0% (7/20), and 25.0% (5/20), respectively. At Week 52, JIA-ACR30/50/70/90 response and inactive disease rates were observed by 88.9% (16/18), 88.9% (16/18), 83.3% (15/18), 66.7% (12/18) and 44.4% (8/18), respectively. CHAQ-DI improved after Week 12. JADAS27-CRP remission and MDA were achieved by 15.0% (3/20) and 45.0% (9/20) of patients at Week 16, and by 50.0% (9/18) and 78.0% (14/18) of patients at Week 52, respectively. The mean abatacept pre-dose serum concentration was above the target therapeutic exposure (10 μg/ml) from Week 8 through Week 16. All adverse events were of mild/moderate intensity, except for one case of severe gastroenteritis. No deaths, malignancies, or autoimmune disorders were observed. No antidrug antibodies were detected through Week 16; one patient had a positive immunogenic response during the cumulative period. Conclusion: Intravenous abatacept was efficacious and well tolerated in Japanese patients with active pJIA

IMSindel: An accurate intermediate-size indel detection tool incorporating de novo assembly and gapped global-local alignment with split read analysis

Abstract Insertions and deletions (indels) have been implicated in dozens of human diseases through the radical alteration of gene function by short frameshift indels as well as long indels. However, the accurate detection of these indels from next-generation sequencing data is still challenging. This is particularly true for intermediate-size indels (≥50 bp), due to the short DNA sequencing reads. Here, we developed a new method that predicts intermediate-size indels using BWA soft-clipped fragments (unmatched fragments in partially mapped reads) and unmapped reads. We report the performance comparison of our method, GATK, PINDEL and ScanIndel, using whole exome sequencing data from the same samples. False positive and false negative counts were determined through Sanger sequencing of all predicted indels across these four methods. The harmonic mean of the recall and precision, F-measure, was used to measure the performance of each method. Our method achieved the highest F-measure of 0.84 in one sample, compared to 0.56 for GATK, 0.52 for PINDEL and 0.46 for ScanIndel. Similar results were obtained in additional samples, demonstrating that our method was superior to the other methods for detecting intermediate-size indels. We believe that this methodology will contribute to the discovery of intermediate-size indels associated with human disease