High-throughput annotation of full-length long noncoding RNAs with Capture Long-Read Sequencing, bioRxiv, 2017-02-02

AbstractAccurate annotations of genes and their transcripts is a foundation of genomics, but no annotation technique presently combines throughput and accuracy. As a result, reference gene collections remain incomplete many gene models are fragmentary, while thousands more remain uncatalogued–particularly for long noncoding RNAs (lncRNAs). To accelerate lncRNA annotation, the GENCODE consortium has developed RNA Capture Long Seq (CLS), combining targeted RNA capture with third-generation long-read sequencing. We present an experimental re-annotation of the GENCODE intergenic lncRNA population in matched human and mouse tissues, resulting in novel transcript models for 3574 561 gene loci, respectively. CLS approximately doubles the annotated complexity of targeted loci, outperforming existing short-read techniques. Full-length transcript models produced by CLS enable us to definitively characterize the genomic features of lncRNAs, including promoter- and gene-structure, and protein-coding potential. Thus CLS removes a longstanding bottleneck of transcriptome annotation, generating manual-quality full-length transcript models at high-throughput scales.Abbreviations<jatsdef-list><jatsdef-item>bpbase pair<jatsdef-item><jatsdef-item>FLfull length<jatsdef-item><jatsdef-item>ntnucleotide<jatsdef-item><jatsdef-item>ROIread of insert, i.e. PacBio read<jatsdef-item><jatsdef-item>SJsplice junction<jatsdef-item><jatsdef-item>SMRTsingle-molecule real-time<jatsdef-item><jatsdef-item>TMtranscript model<jatsdef-item><jatsdef-list>

biorxiv genomics 0-100-users 2017

A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression, bioRxiv, 2017-01-28

AbstractRecent open label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. In order to further test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. Changes in depression severity were assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale (HAM-D). Assessments were made at baseline, and at one (D1), two (D2) and seven (D7) days after dosing. We observed significant antidepressant effects of ayahuasca when compared to placebo at all timepoints. MADRS scores were significantly lower in the ayahuasca group compared to placebo (at D1 and D2 p=0.04; and at D7 p&lt;0.0001). Between-group effect sizes increased from D1 to D7 (D1 Cohen’ s d=0.84; D2 Cohen’ s d=0.84; D7 Cohen’ s d=1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% vs. 27%; p=0.04), while remission rate was marginally significant at D7 (36% vs. 7%, p=0.054). To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression.

biorxiv clinical-trials 0-100-users 2017

 

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