DNA-dependent RNA cleavage by the Natronobacterium gregoryi Argonaute, bioRxiv, 2017-01-21
AbstractWe show here that, unlike most other prokaryotic Argonaute (Ago) proteins, which are DNA-guided endonucleases, the Natronobacterium gregoryi-derived Ago (NgAgo) can function as a DNA-guided endoribonuclease, cleaving RNA, rather than DNA, in a targeted manner. The NgAgo protein, in complex with 5’-hydroxylated or 5’-phosphrylated oligodeoxyribonucleotides (ODNs) of variable lengths, split RNA targets into two or more fragments in vitro, suggesting its physiological role in bacteria and demonstrating a potential for degrading RNA molecules such as mRNA or lncRNA in eukaryotic cells in a targeted manner.
biorxiv biochemistry 0-100-users 2017Rapid de novo assembly of the European eel genome from nanopore sequencing reads, bioRxiv, 2017-01-21
AbstractWe have sequenced the genome of the endangered European eel using the MinION by Oxford Nanopore, and assembled these data using a novel algorithm specifically designed for large eukaryotic genomes. For this 860 Mbp genome, the entire computational process takes two days on a single CPU. The resulting genome assembly significantly improves on a previous draft based on short reads only, both in terms of contiguity (N50 1.2 Mbp) and structural quality. This combination of affordable nanopore sequencing and light-weight assembly promises to make high-quality genomic resources accessible for many non-model plants and animals.
biorxiv genomics 100-200-users 2017Genome Graphs, bioRxiv, 2017-01-19
AbstractThere is increasing recognition that a single, monoploid reference genome is a poor universal reference structure for human genetics, because it represents only a tiny fraction of human variation. Adding this missing variation results in a structure that can be described as a mathematical graph a genome graph. We demonstrate that, in comparison to the existing reference genome (GRCh38), genome graphs can substantially improve the fractions of reads that map uniquely and perfectly. Furthermore, we show that this fundamental simplification of read mapping transforms the variant calling problem from one in which many non-reference variants must be discovered de-novo to one in which the vast majority of variants are simply re-identified within the graph. Using standard benchmarks as well as a novel reference-free evaluation, we show that a simplistic variant calling procedure on a genome graph can already call variants at least as well as, and in many cases better than, a state-of-the-art method on the linear human reference genome. We anticipate that graph-based references will supplant linear references in humans and in other applications where cohorts of sequenced individuals are available.
biorxiv bioinformatics 100-200-users 2017Modern human origins multiregional evolution of autosomes and East Asia origin of Y and mtDNA, bioRxiv, 2017-01-19
AbstractThe neutral theory has been used as a null model for interpreting nature and produced the Recent Out of Africa model of anatomically modern humans. Recent studies, however, have established that genetic diversities are mostly at maximum saturation levels maintained by selection, therefore challenging the explanatory power of the neutral theory and rendering the present molecular model of human origins untenable. Using improved methods and public data, we have revisited human evolution and found sharing of genetic variations among racial groups to be largely a result of parallel mutations rather than recent common ancestry and admixture as commonly assumed. We derived an age of 1.86-1.92 million years for the first split in modern human populations based on autosomal diversity data. We found evidence of modern Y and mtDNA originating in East Asia and dispersing via hybridization with archaic humans. Analyses of autosomes, Y and mtDNA all suggest that Denisovan and Neanderthal were archaic Africans with Eurasian admixtures and ancestors of South Asia Negritos and Aboriginal Australians. Verifying our model, we found more ancestry of Southern Chinese from Hunan in Africans relative to other East Asian groups examined. These results suggest multiregional evolution of autosomes and replacements of archaic Y and mtDNA by modern ones originating in East Asia, thereby leading to a coherent account of modern human origins.
biorxiv evolutionary-biology 0-100-users 2017Untangling intelligence, psychopathy, antisocial personality disorder, & conduct problems A meta-analytic review, bioRxiv, 2017-01-18
AbstractSubstantial research has investigated the association between intelligence and psychopathic traits. The findings to date have been inconsistent and have not always considered the multi-dimensional nature of psychopathic traits. Moreover, there has been a tendency to confuse psychopathy with other closely related, clinically significant disorders. The current study represents a meta-analysis conducted to evaluate the direction and magnitude of the association of intelligence with global psychopathy, as well as its factors and facets, and related disorders (Antisocial Personality Disorder, Conduct Disorder, and Oppositional Defiant Disorder). Our analyses revealed a small, significant, negative relationship between intelligence and total psychopathy (r = -.07, p = .001). Analysis of factors and facets found differential associations, including both significant positive (e.g., interpersonal facet) and negative (e.g., affective facet) associations, further affirming that psychopathy is a multi-dimensional construct. Additionally, intelligence was negatively associated with Antisocial Personality Disorder (r = -.13, p = .001) and Conduct Disorder (r = -.11, p = .001), but positively with Oppositional Defiant Disorder (r = .06, p = .001). There was significant heterogeneity across studies for most effects, but the results of moderator analyses were inconsistent. Finally, bias analyses did not find significant evidence for publication bias or outsized effects of outliers.
biorxiv neuroscience 0-100-users 2017Evaluation of Oxford Nanopore MinIONTM Sequencing for 16S rRNA Microbiome Characterization, bioRxiv, 2017-01-13
AbstractIn this manuscript we evaluate the potential for microbiome characterization by sequencing of near-full length 16S rRNA gene region fragments using the Oxford Nanopore MinION (hereafter ‘Nanopore’) sequencing platform. We analyzed pure-culture E. coli and P. fluorescens, as well as a low-diversity mixed community sample from hydraulic fracturing produced water. Both closed and open reference operational taxonomic unit (OTU) picking failed, necessitating the direct use of sequences without OTU picking. The Ribosomal Database Project classifier against the Green Genes database was found to be the optimal annotation approach, with average pure-culture annotation accuracies of 93.8% and 82.0% at the phyla and genus levels, respectively. Comparative analysis of an environmental sample using Nanopore and Illumina MiSeq sequencing identified high taxonomic similarity when using a weighted metric (Bray-Curtis), and significantly reduced similarity when using an unweighted metric (Jaccard). These results highlight the great potential of Nanopore sequencing to analyze broad microbial community trends, and the challenge of applying Nanopore sequencing to discern rare taxa in mixed microbial communities. Finally, we observed that between-run carryover following washes on the same flowcell accounted for >10% of sequence reads, necessitating future development to either prevent carryover or filter sequences of interest (e.g. barcoding).
biorxiv microbiology 0-100-users 2017