An Efficient Algorithm For Chinese Postman Walk on Bi-directed de Bruijn Graphs

Sequence assembly from short reads is an important problem in biology. It is known that solving the sequence assembly problem exactly on a bi-directed de Bruijn graph or a string graph is intractable. However finding a Shortest Double stranded DNA string (SDDNA) containing all the k-long words in the reads seems to be a good heuristic to get close to the original genome. This problem is equivalent to finding a cyclic Chinese Postman (CP) walk on the underlying un-weighted bi-directed de Bruijn graph built from the reads. The Chinese Postman walk Problem (CPP) is solved by reducing it to a general bi-directed flow on this graph which runs in O(|E|2 log2(|V |)) time. In this paper we show that the cyclic CPP on bi-directed graphs can be solved without reducing it to bi-directed flow. We present a ?(p(|V | + |E|) log(|V |) + (dmaxp)3) time algorithm to solve the cyclic CPP on a weighted bi-directed de Bruijn graph, where p = max{|{v|din(v) - dout(v) > 0}|, |{v|din(v) - dout(v) < 0}|} and dmax = max{|din(v) - dout(v)}. Our algorithm performs asymptotically better than the bidirected flow algorithm when the number of imbalanced nodes p is much less than the nodes in the bi-directed graph. From our experimental results on various datasets, we have noticed that the value of p/|V | lies between 0.08% and 0.13% with 95% probability

Mapping QTL for Fusarium head blight resistance in a tunisian-derived durum wheat population

Fusarium head blight (FHB) damage in durum wheat (Triticum turgidum L. var. durum Desf., turgidum) inflicted massive economic losses worldwide. Meanwhile, FHB resistant durum wheat germplasm is extremely limited. ‘Tunisian108’ is a newly identified tetraploid wheat with FHB resistance. However, genomic regions in ‘Tunisian108’ that significantly associated with FHB resistance are yet unclear. Therefore, a population of 171 backcross inbred lines (BC1F7) derived from a cross between ‘Tunisian108’ and a susceptible durum cultivar ‘Ben’ was characterized. Fusarium graminearum (R010, R1267, and R1322) was point inoculated (greenhouse) or spawn inoculated (field) in 2010 and 2011. Disease severity, Fusarium-damaged kernel (FDK) and mycotoxins were measured. Analysis of variance showed significant genotype and genotype by environment effect on all traits. Approximately 8% of the lines in field and 25% of the lines in greenhouse were more resistance than Tunisian108. A framework linkage map of 267 DArt plus 62 SSR markers was developed representing 239 unique loci and covering a total distance of 1887.6 cM. Composite interval mapping revealed nine QTL for FHB severity, four QTL for DON, and four QTL for FDK on seven chromosomes. Two novel QTL, Qfhb.ndsu-3BL and Qfhb.ndsu-2B, were identified for disease severity, explaining 11 and 6% of the phenotypic variation, respectively. Also, a QTL with large effect on severity and a QTL with negative effect on FDK on chromosome 5A were identified. Importantly, a novel region on chromosome 2B was identified with multiple FHB resistance. Validation on these QTL would facilitate the durum wheat resistance breeding

Towards the first linkage map of the Didymella rabiei genome.

A genetic map was developed for the ascomycete Didymella rabiei (Kovachevski) v. Arx (anamorph: Ascochyta rabiei Pass. Labr.), the causal agent of Ascochyta blight in chickpea (Cicer arietinum L.). The map was generated with 77 F1 progeny derived from crossing an isolate from the U.S.A. and an isolate from Syria. A total of 232 DAF (DNA AmplificationFingerprinting) primers and 37 STMS (Sequence-Tagged Microsatellite Site) primer pairs were tested for polymorphism between the parental isolates; 50 markers were mapped, 36 DAFs and 14 STMSs. These markers cover 261.4cM in ten linkage groups. Nineteen markers remained unlinked. Significant deviation from the expected 1:1 segregation ratios was observed for only two markers (Prob. of x2 <0.05). The implications of our results on ploidy level of the asexual spores are discussed

Chromatin-modifying enzymes as modulators of reprogramming

Generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming involves global epigenetic remodelling. Whereas several proteins are known to regulate chromatin marks associated with the distinct epigenetic states of cells before and after reprogramming, the role of specific chromatin-modifying enzymes in reprogramming remains to be determined. To address how chromatin-modifying proteins influence reprogramming, we used short hairpin RNAs (shRNAs) to target genes in DNA and histone methylation pathways, and identified positive and negative modulators of iPSC generation. Whereas inhibition of the core components of the polycomb repressive complex 1 and 2, including the histone 3 lysine 27 methyltransferase EZH2, reduced reprogramming efficiency, suppression of SUV39H1, YY1 and DOT1L enhanced reprogramming. Specifically, inhibition of the H3K79 histone methyltransferase DOT1L by shRNA or a small molecule accelerated reprogramming, significantly increased the yield of iPSC colonies, and substituted for KLF4 and c-Myc (also known as MYC). Inhibition of DOT1L early in the reprogramming process is associated with a marked increase in two alternative factors, NANOG and LIN28, which play essential functional roles in the enhancement of reprogramming. Genome-wide analysis of H3K79me2 distribution revealed that fibroblast-specific genes associated with the epithelial to mesenchymal transition lose H3K79me2 in the initial phases of reprogramming. DOT1L inhibition facilitates the loss of this mark from genes that are fated to be repressed in the pluripotent state. These findings implicate specific chromatin-modifying enzymes as barriers to or facilitators of reprogramming, and demonstrate how modulation of chromatin-modifying enzymes can be exploited to more efficiently generate iPSCs with fewer exogenous transcription factors. © 2012 Macmillan Publishers Limited. All rights reserved

Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features

Genome-wide association studies have associated thousands of genetic variants with complex traits and diseases, but pinpointing the causal variant(s) among those in tight linkage disequilibrium with each associated variant remains a major challenge. Here, we use seven experimental assays to characterize all common variants at the multiple disease-associated TNFAIP3 locus in five disease-relevant immune cell lines, based on a set of features related to regulatory potential. Trait/disease-associated variants are enriched among SNPs prioritized based on either: (1) residing within CRISPRi-sensitive regulatory regions, or (2) localizing in a chromatin accessible region while displaying allele-specific reporter activity. Of the 15 trait/disease-associated haplotypes at TNFAIP3, 9 have at least one variant meeting one or both of these criteria, 5 of which are further supported by genetic fine-mapping. Our work provides a comprehensive strategy to characterize genetic variation at important disease-associated loci, and aids in the effort to identify trait causal genetic variants

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Exhaustive search of the SNP-SNP interactome identifies epistatic effects on brain volume in two cohorts

The SNP-SNP interactome has rarely been explored in the context of neuroimaging genetics mainly due to the complexity of conducting ∼10 11 pairwise statistical tests. However, recent advances in machine learning, specifically the iterative sure independence screening (SIS) method, have enabled the analysis of datasets where the number of predictors is much larger than the number of observations. Using an implementation of the SIS algorithm (called EPISIS), we used exhaustive search of the genome-wide, SNP-SNP interactome to identify and prioritize SNPs for interaction analysis. We identified a significant SNP pair, rs1345203 and rs1213205, associated with temporal lobe volume. We further examined the full-brain, voxelwise effects of the interaction in the ADNI dataset and separately in an independent dataset of healthy twins (QTIM). We found that each additional loading in the epistatic effect was associated with ∼5% greater brain regional brain volume (a protective effect) in both the ADNI and QTIM samples