Precision-mapping and statistical validation of quantitative trait loci by machine learning

<p>Abstract</p> <p>Background</p> <p>We introduce a QTL-mapping algorithm based on Statistical Machine Learning (SML) that is conceptually quite different to existing methods as there is a strong focus on generalisation ability. Our approach combines ridge regression, recursive feature elimination, and estimation of generalisation performance and marker effects using bootstrap resampling. Model performance and marker effects are determined using independent testing samples (individuals), thus providing better estimates. We compare the performance of SML against Composite Interval Mapping (CIM), Bayesian Interval Mapping (BIM) and single Marker Regression (MR) on synthetic datasets and a multi-trait and multi-environment dataset of the progeny for a cross between two barley cultivars.</p> <p>Results</p> <p>In an analysis of the synthetic datasets, SML accurately predicted the number of QTL underlying a trait while BIM tended to underestimate the number of QTL. The QTL identified by SML for the barley dataset broadly coincided with known QTL locations. SML reported approximately half of the QTL reported by either CIM or MR, not unexpected given that neither CIM nor MR incorporates independent testing. The latter makes these two methods susceptible to producing overly optimistic estimates of QTL effects, as we demonstrate for MR. The QTL resolution (peak definition) afforded by SML was consistently superior to MR, CIM and BIM, with QTL detection power similar to BIM. The precision of SML was underscored by repeatedly identifying, at ≤ 1-cM precision, three QTL for four partially related traits (heading date, plant height, lodging and yield). The set of QTL obtained using a 'raw' and a 'curated' version of the same genotypic dataset were more similar to each other for SML than for CIM or MR.</p> <p>Conclusion</p> <p>The SML algorithm produces better estimates of QTL effects because it eliminates the optimistic bias in the predictive performance of other QTL methods. It produces narrower peaks than other methods (except BIM) and hence identifies QTL with greater precision. It is more robust to genotyping and linkage mapping errors, and identifies markers linked to QTL in the absence of a genetic map.</p

Aluminum tolerance association mapping in triticale

<p>Abstract</p> <p>Background</p> <p>Crop production practices and industrialization processes result in increasing acidification of arable soils. At lower pH levels (below 5.0), aluminum (Al) remains in a cationic form that is toxic to plants, reducing growth and yield. The effect of aluminum on agronomic performance is particularly important in cereals like wheat, which has promoted the development of programs directed towards selection of tolerant forms. Even in intermediately tolerant cereals (i.e., triticale), the decrease in yield may be significant. In triticale, Al tolerance seems to be influenced by both wheat and rye genomes. However, little is known about the precise chromosomal location of tolerance-related genes, and whether wheat or rye genomes are crucial for the expression of that trait in the hybrid.</p> <p>Results</p> <p>A mapping population consisting of 232 advanced breeding triticale forms was developed and phenotyped for Al tolerance using physiological tests. AFLP, SSR and DArT marker platforms were applied to obtain a sufficiently large set of molecular markers (over 3000). Associations between the markers and the trait were tested using General (GLM) and Multiple (MLM) Linear Models, as well as the Statistical Machine Learning (SML) approach. The chromosomal locations of candidate markers were verified based on known assignments of SSRs and DArTs or by using genetic maps of rye and triticale.</p> <p>Two candidate markers on chromosome 3R and 9, 15 and 11 on chromosomes 4R, 6R and 7R, respectively, were identified. The <it>r²</it>values were between 0.066 and 0.220 in most cases, indicating a good fit of the data, with better results obtained with the GML than the MLM approach. Several QTLs on rye chromosomes appeared to be involved in the phenotypic expression of the trait, suggesting that rye genome factors are predominantly responsible for Al tolerance in triticale.</p> <p>Conclusions</p> <p>The Diversity Arrays Technology was applied successfully to association mapping studies performed on triticale breeding forms. Statistical approaches allowed the identification of numerous markers associated with Al tolerance. Available rye and triticale genetic maps suggested the putative location of the markers and demonstrated that they formed several linked groups assigned to distinct chromosomes (3R, 4R, 6R and 7R). Markers associated with genomic regions under positive selection were identified and indirectly mapped in the vicinity of the Al-tolerant markers. The present findings were in agreement with prior reports.</p

Deegoization as the Aim of Education – the Soul Paradigm

The article focuses on man understood as a being that exists in the imaginary order and displays the ability to create images. One of the these images is the ego construct which will be revisioned in the perspective of the critical psychology of Kurt Danziger and the imaginal psychology/soul paradigm (soul movement) of James Hillman. The critical analysis points out a specific reduction of human nature and human history in contemporary psychology to the history of “self” and domination of “ego”. The conception of Hillman, by contrast, is characterized by the mission for deegoization, therefore strips the power away from this fictitious concept in favor of a realistically existing soul which not only can exceed the ego, but also a personality, or even the whole human being because it contains a variety of images. Hillman believes, following Plato, in the existence of anima mundi, an ensouled world, which is wide and more primal than the ego, but also a human soul, because the soul is a part of it. In accordance with this perspective, the role of a parent and teacher in the process of education is deegoization as a condition for the soul-making of a child.Artykuł traktuje o człowieku jako istocie funkcjonującej w porządku wyobrażonym i zdolnej do tworzenia obrazów. Jednym z tych obrazów jest konstrukt ego przedstawiony w perspektywie psychologii krytycznej Kurta Danzigera oraz psychologii imaginalnej/paradygmat duszy (soul movement) Jamesa Hillmana. Autorzy wprowadzają te dwa podejścia celem zasygnalizowania obszaru badawczego, który potencjalnie może być wykorzystany we współczesnej refleksji nad kategorią wychowania. Analiza krytyczna wskazuje na swoistą redukcję natury ludzkiej i historii człowieka we współczesnej psychologii do historii „ja” i dominacji „ego”. Natomiast koncepcję Hillmana charakteryzuje misja deegoizacji, a więc pozbawienia siły tego fikcyjnego konstruktu, na rzecz realnie istniejącej duszy, która nie tylko ma wymiar przekraczający ego, bo zawiera w sobie wielość innych obrazów, ale także osobowość, a nawet osobę ludzką. Hillman uznaje bowiem za Platonem istnienie anima mundi, czyli ensouled world, która jest szersza i pierwotna wobec nie tylko ego, ale i duszy ludzkiej, a której owa dusza jest składową. Zgodnie z tą perspektywą, w procesie wychowania rolą rodzica i nauczyciela staje się deegoizacja jako warunek stwarzania duszy dziecka (soul-making)

Single Nucleotide Polymorphisms (SNPs) reveal sibship among founders of a Bangladeshi rohu (Labeo rohita) breeding population

Rohu (Labeo rohita) is a significant freshwater aquaculture species with approximately 1.8 Mt produced annually. Fin clips obtained from the founders of a newly established Bangladesh-based breeding population (~140 fish from each of the Halda, Jamuna and Padma rivers) were used to identify 9157 SNPs and 14 411 silicoDArT markers using the Diversity Arrays Technology (DArT) genotyping-by-sequencing platform known as using the DArTseqTM platform. After quality control, 1985 SNPs were retained and used to examine population structure within and among river systems. Examination of genomic relationships revealed evidence of full- and half-sibling relationships among founders. Accordingly, sibship and dummy parents were assigned within each river population using a maximum likelihood approach with COLONY software. Founders that had no dummy parents in common were then identified for population genetic analyses. Only 40 unique dummy parents and 17 founders with no common dummy parents were identified from the Halda river, compared with 206 (96) from the Jamuna and 184 (83) from the Padma. Overall pairwise FST estimates among rivers were low (< 0.005) and the optimum number of clusters using unsupervised K-means clustering was one, indicating little genetic divergence among the river populations in our SNPs. These results suggest that observed sibship among founders should be accounted for in future pedigree-based analyses and it cannot be assumed that fertilised spawn collections are representative samples of river populations

A DArT platform for quantitative bulked segregant analysis

<p>Abstract</p> <p>Background</p> <p>Bulked segregant analysis (BSA) identifies molecular markers associated with a phenotype by screening two DNA pools of phenotypically distinct plants for markers with skewed allele frequencies. In contrast to gel-based markers, hybridization-based markers such as SFP, DArT or SNP generate quantitative allele-frequency estimates. Only DArT, however, combines this advantage with low development and assay costs and the ability to be deployed for any plant species irrespective of its ploidy level. Here we investigate the suitability of DArT for BSA applications using a barley array as an example.</p> <p>Results</p> <p>In a first test experiment, we compared two bulks of 40 Steptoe/Morex DH plants with contrasting pubescent leaves (mPub) alleles on chromosome 3H. At optimized levels of experimental replication and marker-selection threshold, the BSA scan identified 433 polymorphic markers. The relative hybridization contrast between bulks accurately reflected the between-bulk difference in the frequency of the mPub allele (r = 0.96). The 'platform noise' of DArT assays, estimated by comparing two identical aliquots of a DNA mixture, was significantly lower than the 'pooling noise' reflecting the binomial sampling variance of the bulking process. The allele-frequency difference on chromosome 3H increased in the vicinity of mPub and peaked at the marker with the smallest distance from mPub (4.6 cM). In a validation experiment with only 20 plants per bulk we identified an aluminum (Al) tolerance locus in a Dayton/Zhepi2 DH population on chromosome 4H with < 0.8 cM precision, the same Al-tolerance locus that had been mapped before in other barley populations.</p> <p>Conclusion</p> <p>DArT-BSA identifies genetic loci that influence phenotypic characters in barley with at least 5 cM accuracy and should prove useful as a generic tool for high-throughput, quantitative BSA in plants irrespective of their ploidy level.</p

A MITE-based genotyping method to reveal hundreds of DNA polymorphisms in an animal genome after a few generations of artificial selection

<p>Abstract</p> <p>Background</p> <p>For most organisms, developing hundreds of genetic markers spanning the whole genome still requires excessive if not unrealistic efforts. In this context, there is an obvious need for methodologies allowing the low-cost, fast and high-throughput genotyping of virtually any species, such as the Diversity Arrays Technology (DArT). One of the crucial steps of the DArT technique is the genome complexity reduction, which allows obtaining a genomic representation characteristic of the studied DNA sample and necessary for subsequent genotyping. In this article, using the mosquito <it>Aedes aegypti </it>as a study model, we describe a new genome complexity reduction method taking advantage of the abundance of miniature inverted repeat transposable elements (MITEs) in the genome of this species.</p> <p>Results</p> <p><it>Ae. aegypti </it>genomic representations were produced following a two-step procedure: (1) restriction digestion of the genomic DNA and simultaneous ligation of a specific adaptor to compatible ends, and (2) amplification of restriction fragments containing a particular MITE element called <it>Pony </it>using two primers, one annealing to the adaptor sequence and one annealing to a conserved sequence motif of the <it>Pony </it>element. Using this protocol, we constructed a library comprising more than 6,000 DArT clones, of which at least 5.70% were highly reliable polymorphic markers for two closely related mosquito strains separated by only a few generations of artificial selection. Within this dataset, linkage disequilibrium was low, and marker redundancy was evaluated at 2.86% only. Most of the detected genetic variability was observed between the two studied mosquito strains, but individuals of the same strain could still be clearly distinguished.</p> <p>Conclusion</p> <p>The new complexity reduction method was particularly efficient to reveal genetic polymorphisms in <it>Ae. egypti</it>. Overall, our results testify of the flexibility of the DArT genotyping technique and open new prospects as regards its application to a wider range of species, including animals which have been refractory to it so far. DArT has also a role to play in the current burst of whole-genome scans carried out in various organisms, which track signatures of selection in order to unravel the basis of genetic adaptation.</p