Main findings and advances in bioinformatics and biomedical engineeringIWBBIO 2018

We want to thank the great work done by the reviewers of each of the papers, together with the great interest shown by the editorial of BMC Bioinformatics in IWBBIO Conference. Special thanks to D. Omar El Bakry for his interest and great help to make this Special Issue. Thank the Ministry of Spain for the economic resources within the project with reference RTI2018-101674-B-I00.In the current supplement, we are proud to present seventeen relevant contributions from the 6th International Work-Conference on Bioinformatics and Biomedical Engineering (IWBBIO 2018), which was held during April 25-27, 2018 in Granada (Spain). These contributions have been chosen because of their quality and the importance of their findings.This research has been partially supported by the proyects with reference RTI2018-101674-B-I00 (Ministry of Spain) and B-TIC-414-UGR18 (FEDER, Junta Andalucia and UGR)

The utility of single nucleotide polymorphisms in inferences of population history

Single nucleotide polymorphisms (SNPs) represent the most widespread type of sequence variation in genomes, yet they have only emerged recently as valuable genetic markers for revealing the evolutionary history of populations. Their occurrence throughout the genome also makes them ideal for analyses of speciation and historical demography, especially in light of recent theory suggesting that many unlinked nuclear loci are needed to estimate population genetic parameters with statistical confidence. In spite of having lower variation compared with microsatellites, SNPs should make the comparison of genomic diversities and histories of different species (the core goal of comparative biogeography) more straightforward than has been possible with microsatellites. The most pervasive, but correctable, complication to SNP analysis is a bias towards analyzing only the most variable loci, an artifact that is usually introduced by the limited number of individuals used to screen initially for polymorphisms. Although the use of SNPs as markers in population studies is still new, innovative methods for SNP identification, automated screening, haplotype inference and statistical analysis might quickly make SNPs the marker of choice

The transcriptomic and genomic architecture of acrididae grasshoppers

Genetic polymorphism is described as the variation in DNA sequence between distinct individuals of a given species or population. This polymorphism is reflected from individuals to entire populations, and from single nucleotides to the entire genome spanning billions of base pairs. A fundamental aim of functional genomics is to establish links between genetic polymorphism and phenotypic variation, to explain this observed variation. Recent developments in high throughput sequencing have made it possible to adequately explore this link. My dissertation explores genetic and genomic polymorphism in Gomphocerine grasshoppers, an insect group with unusually large and complex genomes using novel and contemporary transcriptomic and genomic methods.Genetische Polymorphismen beschreiben die Variation in DNS-Sequenzen zwischen Individuen einer Art oder zwischen Populationen. Die genetischen Polymorphismen zwischen Individuen bis zu ganzen Population und von Punktmutationen zu ganzen Genomen umfassen Milliarden von Basenpaaren. Ein fundamentales Ziel funktioneller Genomik ist es, den Zusammenhang von genetischen Polymorphismen und phänotypischer Variation zu verstehen. Neuste Entwicklungen in der Hochdurchsatzsequenzierung haben es möglich gemacht, diesen Zusammenhang umfassend zu explorieren. Meine Dissertation ergründet genetische und genomische Polymorphismen in Heuschrecken der Unterfamilie Gomphocerinae, einer Insektengruppe mit ungewöhnlich großen und komplexen Genomen, mittels moderner transkriptomischer und genomischer Methoden

Statistical Genomics and Bioinformatics

Some important and interesting topics in the newly emerging disciplines of Statistical genomics andbioinformatics have been discussed briefly in relation to plants with possible references to fruit crops. This paper is therefore divided into two parts relating to the two disciplines, respectively. In the first part, mapping of quantitative trait loci (QTL), association mapping, mapping of gene expression transcripts (eQTL), marker-assisted selection, and a systems approach to quantitative genetics have been dealt with. In the second part, generation of databases, annotation, annotated sequence databases, and sequence similarity search have been described

Discovery and population genomics of structural variation in a songbird genus

Structural variation (SV) constitutes an important type of genetic mutations providing the raw material for evolution. Here, we uncover the genome-wide spectrum of intra- and interspecific SV segregating in natural populations of seven songbird species in the genus Corvus. Combining short-read (N = 127) and long-read re-sequencing (N = 31), as well as optical mapping (N = 16), we apply both assembly- and read mapping approaches to detect SV and characterize a total of 220,452 insertions, deletions and inversions. We exploit sampling across wide phylogenetic timescales to validate SV genotypes and assess the contribution of SV to evolutionary processes in an avian model of incipient speciation. We reveal an evolutionary young (~530,000 years) cis-acting 2.25-kb LTR retrotransposon insertion reducing expression of the NDP gene with consequences for premating isolation. Our results attest to the wealth and evolutionary significance of SV segregating in natural populations and highlight the need for reliable SV genotyping

A likelihood ratio based method to predict exact pedigrees for complex families from next-generation sequencing data

MOTIVATION: Next generation sequencing (NGS) technology considerably changed the way we screen for pathogenic mutations in rare Mendelian disorders. However, the identification of the disease- causing mutation amongst thousands of variants of partly unknown relevance is still challenging and efficient techniques that reduce the genomic search space play a decisive role. Often segregation- or linkage analysis are used to prioritize candidates, however, these approaches require correct information about the degree of relationship among the sequenced samples. For quality assurance an automated control of pedigree structures and sample assignment is therefore highly desirable in order to detect label mix-ups that might otherwise corrupt downstream analysis. RESULTS: We developed an algorithm based on likelihood ratios that discriminates between different classes of relationship for an arbitrary number of genotyped samples. By identifying the most likely class we are able to reconstruct entire pedigrees iteratively, even for highly consanguineous families. We tested our approach on exome data of different sequencing studies and achieved high precision for all pedigree predictions. By analyzing the precision for varying degrees of relatedness or inbreeding we could show that a prediction is robust down to magnitudes of a few hundred loci. AVAILABILITY: A java standalone application that computes the relationships between multiple samples as well as a Rscript that visualizes the pedigree information is available for download as well as a web service at www.gene-talk.de CONTACT: [email protected]

A shot in the genome: how accurately do shotgun 454 sequences represent a genome?

BACKGROUND: Next generation sequencing (NGS) provides a valuable method to quickly obtain sequence information from non-model organisms at a genomic scale. In principle, if sequencing is not targeted for a genomic region or sequence type (e.g. coding region, microsatellites) NGS reads can be used as a genome snapshot and provide information on the different types of sequences in the genome. However, no study has ascertained if a typical 454 dataset of low coverage (1/4-1/8 of a PicoTiter plate leading to generally less than 0.1x of coverage) represents all parts of genomes equally. FINDINGS: Partial genome shotgun sequencing of total DNA (without enrichment) on a 454 NGS platform was used to obtain reads of Apis mellifera (454 reads hereafter). These 454 reads were compared to the assembled chromosomes of this species in three different aspects: (i) dimer and trimer compositions, (ii) the distribution of mapped 454 sequences along the chromosomes and (iii) the numbers of different classes of microsatellites. Highly significant chi-square tests for all three types of analyses indicated that the 454 data is not a perfect random sample of the genome. Only the number of 454 reads mapped to each of the 16 chromosomes and the number of microsatellites pooled by motif (repeat unit) length was not significantly different from the expected values. However, a very strong correlation (correlation coefficients greater than 0.97) was observed between most of the 454 variables (the number of different dimers and trimers, the number of 454 reads mapped to each chromosome fragments of one Mb, the number of 454 reads mapped to each chromosome, the number of microsatellites of each class) and their corresponding genomic variables. CONCLUSIONS: The results of chi square tests suggest that 454 shotgun reads cannot be regarded as a perfect representation of the genome especially if the comparison is done on a finer scale (e.g. chromosome fragments instead of whole chromosomes). However, the high correlation between 454 and genome variables tested indicate that a high proportion of the variability of 454 variables is explained by their genomic counterparts. Therefore, we conclude that using 454 data to obtain information on the genome is biologically meaningful.Emese Meglécz, Nicolas Pech, André Gilles, Jean-François Martin and Michael G Gardne

Characterisation of the population genetics of farm-bred Haliotis midae using microsatellite DNA markers

Includes bibliographical references (leaves 89-94).The abalone Haliotis midae is a gastropod mollusc which is of commercial importance in South Africa due to its high export value. During this study the genetic structure of farmed Haliotis midae was investigated in order to determine whether microsatellite DNA analysis could be used to separate farmed abalone into phenotypically different groups with respect to growth rate. Microsatellites display high levels of variability and this makes them suitable for a wide variety of applications in aquaculture, particularly where genetic differentiation between population groups may be limited. This study investigates the genetic composition of 120 individuals from 2 spawning events that had been classed as either fast or slow growing by the farm managers. Three highly polymorphic microsatellite loci were selected and used to determine the extent of the genetic diversity which exists amongst the 120 individuals tested from the lacobsbaai abalone farm. Additionally, these microsatellite loci were used to determine whether abalone classed as either fast or slow growing could be differentiated into specific genetic population groups. Neighbour-joining trees constructed using genetic distance data obtained for all three loci demonstrated that a distinct separation between the fast and slow growing abalone was evident. It was also found that there has been a loss of genetic diversity on the lacobsbaai abalone farm in terms of heterozygosity. This has been attributed to the high levels of inbreeding as evidenced by the high Fis values. All population groups were found to deviate significantly from Hardy-Weinberg equilibrium and this is most likely due to the occurrence of non-random mating on the lacobsbaai abalone farm. This study has successfully demonstrated that a combination of micro satellite loci with high allelic diversity can potentially be employed as a tool for distinguishing between fast and slow growing farmed abalone. This study needs to be validated by testing larger sample sizes and the use of additional farms

Genetic analysis of European seabass (Dicentrarchus Labrax L.) from Portuguese waters using allozyme and microsatellite loci

Genetic differentiation among juvenile samples of the European seabass (Dicentrarchus labrax) from the coast of Portugal is reported by means of two types of genetic markers: allozymes and microsatellites. Repeat samples were taken from 5 different nursery grounds (Aveiro, Foz, Obidos, Milfontes and Faro) along the coast of Portugal between November 1992 and February 1994. Starch-gel electrophoresis was used to assess the level and distribution of genetic variability of 38 loci. Six of these were found to be polymorphic at the 99% level and were used in population surveys: AAT-3*, ADA *, GPI-I *, GPI-2*, G3PDH-2*, SOD*. Statistical analysis revealed low but statistically significant multilocus F.'I (0.0108, p<O.OOI) values suggesting that population structuring exists along the Portuguese coast line. The results indicate that there is some restriction in gene flow between the more southerly population at Faro and all other sites to the North. Five microsatellite loci were screened in over 300 individuals. High levels of polymorphism (number of alleles observed per locus ranged from 20 to 41) and observed heterozygosities, ranging from 0.45 to 0.89 (mean over all loci = 0.71) were detected. Two loci displayed heterozygosity deficits (Dla6 and Labrax-9) and were not used in population comparisons. Statistical analysis revealed low but statistically significant multilocus FST (0.0025, p<O.OOl) at the other three loci (Dlall, Labrax-3 and Labrax-8). No clear geographic patterns emerged from these results. Overall allozymes performed well when compared to microsatellites, in detecting microgeographic genetic structure in this species. Microsatellites revealed high levels of polymorphism that should prove useful as markers in the management of wild and farmed seabass stocks in the future. The level of differentiation, low values of F ST , detected among the sites is low but is typical of marine species which have a much greater chance of mixing

Historical demography and genetic differentiation of the giant freshwater prawn Macrobrachium rosenbergii in Bangladesh based on mitochondrial and ddRAD sequence variation

Macrobrachium rosenbergii, the giant freshwater prawn, is an important source of high quality protein and occurs naturally in rivers as well as commercial farms in South and South-East Asia, including Bangladesh. This study investigated the genetic variation and population structure of M. rosenbergii sampled from four rivers in Bangladesh (sample size ranged from 19 to 20), assessing sequence variation, both in the mitochondrial cytochrome oxidase subunit 1 (CO1) gene and in 106 single nucleotide polymorphisms (SNPs) sampled randomly from the genome with double digest RAD sequencing (ddRADseq). The mitochondrial variation presented a shallow genealogy with high haplotype diversity (h = 0.95), reflecting an expansion in population size for the last ~82 kyr. Based on the CO1 variation the current effective population size (Ne) was 9.7 × 106 (CI: 1.33 × 106 – 35.84 × 106) individuals. A significant population differentiation was observed with the mitochondrial CO1 sequence variation and based on the ddRADseq variation, which could be traced to the divergence of the population in the Naf River in the South-East border with Myanmar from the other populations. A differentiation in mtDNA haplotype frequencies was also observed between the Biskhali River and the Karnaphuli Rivers in eastern Bangladesh. This study demonstrated the use of high-throughput genotyping based on the ddRADseq method to reveal population structure at a small geographical scale for an important freshwater prawn. The information from this study can be utilized for management and conservation of this species in Bangladesh.United Nations University Fisheries Training Programme (UNUFTP), IcelandPeer Reviewe