Comparison of tagging single-nucleotide polymorphism methods in association analyses

Several methods to identify tagging single-nucleotide polymorphisms (SNPs) are in common use for genetic epidemiologic studies; however, there may be loss of information when using only a subset of SNPs. We sought to compare the ability of commonly used pairwise, multimarker, and haplotype-based tagging SNP selection methods to detect known associations with quantitative expression phenotypes. Using data from HapMap release 21 on unrelated Utah residents with ancestors from northern and western Europe (CEPH-Utah, CEU), we selected tagging SNPs in five chromosomal regions using ldSelect, Tagger, and TagSNPs. We found that SNP subsets did not substantially overlap, and that the use of trio data did not greatly impact SNP selection. We then tested associations between HapMap genotypes and expression phenotypes on 28 CEU individuals as part of Genetic Analysis Workshop 15. Relative to the use of all SNPs (n = 210 SNPs across all regions), most subset methods were able to detect single-SNP and haplotype associations. Generally, pairwise selection approaches worked extremely well, relative to use of all SNPs, with marked reductions in the number of SNPs required. Haplotype-based approaches, which had identified smaller SNP subsets, missed associations in some regions. We conclude that the optimal tagging SNP method depends on the true model of the genetic association (i.e., whether a SNP or haplotype is responsible); unfortunately, this is often unknown at the time of SNP selection. Additional evaluations using empirical and simulated data are needed

Taking on a Community Solutions Process (Co-Solve) to the Pain and Opioid Epidemic: A Multi-disciplinary and Multi-institute Pain Panel and Community Response in Sacramento, California

America’s healthcare providers and patients are challenged by an overwhelming high prevalence of chronic pain and opioid misuse. Approximately 23.4 million adults suffer from daily pain and in 2014, nearly 61% of Americans who died from drug overdoses used an opioid analgesic. Unrecognized addiction, untreated psychiatric comorbidity, and lack of training/education for providers and patients are factors associated with chronic pain and opioid misuse. Communication strategies and structures are required to enhance collaboration between multidisciplinary providers and institutions. On September 28, 2017, an open panel discussion with pain specialists from three major academic and medical institutes in Sacramento, California initiated an integrative community solutions process to optimize pain education best practices and to protect public health. The attendees represented a wide range of healthcare disciplines. This commentary describes ideas derived from dialogue between community attendees and panelists, which considers both healthcare provider characteristics and patients’ cultural backgrounds. Providers of most disciplines underscored the need to share information and institute cross-disciplinary training on pain and behavioral health treatments. In conclusion, we outline an integrative community-based framework, namely the Community Solutions Process (Co-Solve), to help other communities to implement and derive their own action-oriented solutions unique to their population

Corrigendum:Comprehensive Molecular Characterization of Escherichia coli Isolates from Urine Samples of Hospitalized Patients in Rio de Janeiro, Brazil (Frontiers in Microbiology, (2018), 9, (243), 10.3389/fmicb.2018.00243)

[This corrects the article DOI: 10.3389/fmicb.2018.00243.]

Determining the virulence properties of Escherichia coli ST131 containing bacteriocin-encoding plasmids using short-and long-read sequencing and comparing them with those of other E. Coli lineages

T. Escherichia coli ST131 is a clinical challenge due to its multidrug resistant profile and successful global spread. They are often associated with complicated infections, particularly urinary tract infections (UTIs). Bacteriocins play an important role to outcompete other microorganisms present in the human gut. Here, we characterized bacteriocin-encoding plasmids found in ST131 isolates of patients suffering from a UTI using both short-and long-read sequencing. Colicins Ia, Ib and E1, and microcin V, were identified among plasmids that also contained resistance and virulence genes. To investigate if the potential transmission range of the colicin E1 plasmid is influenced by the presence of a resistance gene, we constructed a strain containing a plasmid which had both the colicin E1 and blaCMY-2 genes. No difference in transmission range was found between transformant and wild-type strains. However, a statistically significantly difference was found in adhesion and invasion ability. Bacteriocin-producing isolates from both ST131 and non-ST131 lineages were able to inhibit the growth of other E. coli isolates, including other ST131. In summary, plasmids harboring bacteriocins give additional advantages for highly virulent and resistant ST131 isolates, improving the ability of these isolates to compete with other microbiota for a niche and thereby increasing the risk of infection

Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum

Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism

Hantavirus Pulmonary Syndrome, Central Plateau, Southeastern, and Southern Brazil

This syndrome is an increasing health problem because of human encroachment into habitats of rodent reservoirs

Phase 2 Study of the Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Men Who Have Sex With Men (HPTN 069/ACTG A5305)

Maraviroc (MVC) is a candidate for human immunodeficiency virus (HIV) pre-exposure prophylaxis