On the importance of being finished

The publication of an increasing number of draft genome sequences presents problems that will only be resolved by improved search tools and by complete finishing of the sequences - and their deposition in publicly accessible databases

How IBD patients cope with IBD: A systematic review

AbstractObjectiveInflammatory bowel disease (IBD) can have a significant impact on psychological wellbeing and quality of life. How one responds to and copes with IBD may be an important determinant of psychological wellbeing. We aimed to systematically review all published literature regarding coping strategies of IBD patients.MethodsOvid and Pubmed databases were searched over 6months. All articles about coping strategies of IBD patients were included.ResultsThirty-nine articles using twenty-two survey instruments were found, of which twenty-six were adult exclusive, eleven were children exclusive, and two had both adults and children. Two were interventional, four were longitudinal, and the rest were cross-sectional studies. Four studies were qualitative while the rest used quantitative measures. Variance in research designs and coping instruments led to inconsistent results. The most common theme was that emotion-focused coping was associated with worse psychological outcomes, while the effect of problem-focused coping was less consistently associated with better psychological outcomes.ConclusionsMore longitudinal and interventional studies are needed to causally link coping strategies with psychological outcomes in IBD patient

Does Computerized Cognitive Behavioral Therapy Help People with Inflammatory Bowel Disease? : A Randomized Controlled Trial

BACKGROUND: Cognitive behavioral therapy may be useful for improving health-related quality of life (HRQOL) of at least some patients with inflammatory bowel disease (IBD), especially those with psychiatric comorbidities. However, cognitive behavioral therapy can be difficult to access. These difficulties can be overcome by computerized cognitive behavioral therapy (CCBT). This is a randomized controlled trial of a self-administered CCBT intervention for patients with IBD focused on improving HRQOL. It is hypothesized that CCBT completers will have an improved HRQOL relative to people not allocated to CCBT. METHODS: Patients with IBD were randomly allocated to CCBT (n = 113) versus treatment as usual (n = 86). The IBD Questionnaire at 12 weeks after baseline was the primary outcome, while generic HRQOL, anxiety, depression, coping strategies, perceived stress, and IBD symptoms were secondary outcomes. Outcomes were also measured at 6 months after baseline. Predictors of dropout were also determined. RESULTS: Twenty-nine CCBT participants (25.7%) completed the CCBT. The IBD Questionnaire was significantly increased at 12 weeks in CCBT completers compared with treatment-as-usual patients (F = 6.38, P = 0.01). Short Form-12 mental score (F = 5.00, P = 0.03) was also significantly better in CCBT compared with treatment-as-usual patients at 12 weeks. These outcomes were not maintained at 6 months. The predictors of dropout were baseline depression, biological use, lower IBD Questionnaire scores, and not having steroids. CONCLUSIONS: Improvements at 12 weeks after baseline were not maintained at 6 months. Future research should aim to improve adherence rates. Moreover, CCBT may not work for patients with IBD with comorbid depression

A comparative analysis of exome capture

ABSTRACT: BACKGROUND: Human exome resequencing using commercial target capture kits has been and is being used for sequencing large numbers of individuals to search for variants associated with various human diseases. We rigorously evaluated the capabilities of two solution exome capture kits. These analyses help clarify the strengths and limitations of those data as well as systematically identify variables that should be considered in the use of those data. RESULTS: Each exome kit performed well at capturing the targets they were designed to capture, which mainly corresponds to the consensus coding sequences (CCDS) annotations of the human genome. In addition, based on their respective targets, each capture kit coupled with high coverage Illumina sequencing produced highly accurate nucleotide calls. However, other databases, such as the Reference Sequence collection (RefSeq), define the exome more broadly, and so not surprisingly, the exome kits did not capture these additional regions. CONCLUSIONS: Commercial exome capture kits provide a very efficient way to sequence select areas of the genome at very high accuracy. Here we provide the data to help guide critical analyses of sequencing data derived from these products

Era of gapless plant genomes: innovations in sequencing and mapping technologies revolutionize genomics and breeding

Whole-genome sequencing and assembly have revolutionized plant genetics and molecular biology over the last two decades. However, significant shortcomings in first- and second-generation technology resulted in imperfect reference genomes: numerous and large gaps of low quality or undeterminable sequence in areas of highly repetitive DNA along with limited chromosomal phasing restricted the ability of researchers to characterize regulatory noncoding elements and genic regions that underwent recent duplication events. Recently, advances in long-read sequencing have resulted in the first gapless, telomere-to-telomere (T2T) assemblies of plant genomes. This leap forward has the potential to increase the speed and confidence of genomics and molecular experimentation while reducing costs for the research community

EST analysis in Ginkgo biloba: an assessment of conserved developmental regulators and gymnosperm specific genes

BACKGROUND: Ginkgo biloba L. is the only surviving member of one of the oldest living seed plant groups with medicinal, spiritual and horticultural importance worldwide. As an evolutionary relic, it displays many characters found in the early, extinct seed plants and extant cycads. To establish a molecular base to understand the evolution of seeds and pollen, we created a cDNA library and EST dataset from the reproductive structures of male (microsporangiate), female (megasporangiate), and vegetative organs (leaves) of Ginkgo biloba. RESULTS: RNA from newly emerged male and female reproductive organs and immature leaves was used to create three distinct cDNA libraries from which 6,434 ESTs were generated. These 6,434 ESTs from Ginkgo biloba were clustered into 3,830 unigenes. A comparison of our Ginkgo unigene set against the fully annotated genomes of rice and Arabidopsis, and all available ESTs in Genbank revealed that 256 Ginkgo unigenes match only genes among the gymnosperms and non-seed plants – many with multiple matches to genes in non-angiosperm plants. Conversely, another group of unigenes in Gingko had highly significant homology to transcription factors in angiosperms involved in development, including MADS box genes as well as post-transcriptional regulators. Several of the conserved developmental genes found in Ginkgo had top BLAST homology to cycad genes. We also note here the presence of ESTs in G. biloba similar to genes that to date have only been found in gymnosperms and an additional 22 Ginkgo genes common only to genes from cycads. CONCLUSION: Our analysis of an EST dataset from G. biloba revealed genes potentially unique to gymnosperms. Many of these genes showed homology to fully sequenced clones from our cycad EST dataset found in common only with gymnosperms. Other Ginkgo ESTs are similar to developmental regulators in higher plants. This work sets the stage for future studies on Ginkgo to better understand seed and pollen evolution, and to resolve the ambiguous phylogenetic relationship of G. biloba among the gymnosperms

Genome and transcriptome of the regeneration-competent flatworm, Macrostomum lignano.

The free-living flatworm, Macrostomum lignano has an impressive regenerative capacity. Following injury, it can regenerate almost an entirely new organism because of the presence of an abundant somatic stem cell population, the neoblasts. This set of unique properties makes many flatworms attractive organisms for studying the evolution of pathways involved in tissue self-renewal, cell-fate specification, and regeneration. The use of these organisms as models, however, is hampered by the lack of a well-assembled and annotated genome sequences, fundamental to modern genetic and molecular studies. Here we report the genomic sequence of M. lignano and an accompanying characterization of its transcriptome. The genome structure of M. lignano is remarkably complex, with ∼75% of its sequence being comprised of simple repeats and transposon sequences. This has made high-quality assembly from Illumina reads alone impossible (N50=222 bp). We therefore generated 130× coverage by long sequencing reads from the Pacific Biosciences platform to create a substantially improved assembly with an N50 of 64 Kbp. We complemented the reference genome with an assembled and annotated transcriptome, and used both of these datasets in combination to probe gene-expression patterns during regeneration, examining pathways important to stem cell function.This work is supported by National Institutes of Health Grants R37 GM062534 (to G.J.H.) and R01-HG006677 (to M.S.); National Science Foundation Grant DBI-1350041 (to M.S.); and a Swiss National Science Foundation Grant 31003A-143732 (to L.S.). This work was performed with assistance from Cold Spring Harbor Laboratory Shared Resources, which are funded, in part, by Cancer Center Support Grant 5P30CA045508.This is the final version of the article. It first appeared from PNAS via http://dx.doi.org/10.1073/pnas.151671811

Unraveling molecular mechanisms of immunity and cancer-resistance using the genomes of the Neotropical bats Artibeus jamaicensis and Pteronotus mesoamericanus

Bats are exceptional among mammals for harbouring diverse pathogens and for their robust immune systems. In addition, bats are unusually long-lived and show low rates of cancer. Contiguous and complete reference genomes are needed to determine the genetic basis of these adaptations and establish bats as models for research into mammalian health. Here we sequenced and analysed the genomes of the Jamaican fruit bat ( Artibeus jamaicensis ) and the Mesoamerican mustached bat ( Pteronotus mesoamericanus ). We sequenced these two species using a mix of Illumina and Oxford Nanopore Technologies (ONT), assembling draft genomes with some of the highest contig N50s (28-29Mb) of bat genomes to date. Work is in progress to increase the base-level accuracies of these genomes. We conducted gene annotation and identified a set of 10,928 orthologs from bats and mammalian outgroups including humans, rodents, horses, pigs, and dogs. To detect positively selected genes as well as lineage-specific gene gains and losses, we carried out comprehensive branch-site likelihood ratio tests and gene family size analyses. Our analysis found signatures of rapid evolution in the innate immune response genes of bats, and evidence of past infections with diverse viral clades in Artibeus jamaicensis and Pteronotus mesoamericanus . We additionally found evidence of positive selection of tumor suppressors, which may play a role in the low cancer rates, in the most recent common ancestor of bats. These new genomic resources enable insights into the extraordinary adaptations of bats, with implications for mammalian evolutionary studies and public health

DNA sequence level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders

Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes