Machine learning meets genome assembly Padovani de Souza, Kleber; Setubal, João Carlos; Ponce de Leon F. de Carvalho, André Carlos ...
Briefings in bioinformatics,
11/2019, Letnik:
20, Številka:
6
Journal Article
Recenzirano
Abstract
Motivation: With the recent advances in DNA sequencing technologies, the study of the genetic composition of living organisms has become more accessible for researchers. Several advances ...have been achieved because of it, especially in the health sciences. However, many challenges which emerge from the complexity of sequencing projects remain unsolved. Among them is the task of assembling DNA fragments from previously unsequenced organisms, which is classified as an NP-hard (nondeterministic polynomial time hard) problem, for which no efficient computational solution with reasonable execution time exists. However, several tools that produce approximate solutions have been used with results that have facilitated scientific discoveries, although there is ample room for improvement. As with other NP-hard problems, machine learning algorithms have been one of the approaches used in recent years in an attempt to find better solutions to the DNA fragment assembly problem, although still at a low scale.
Results: This paper presents a broad review of pioneering literature comprising artificial intelligence-based DNA assemblers—particularly the ones that use machine learning—to provide an overview of state-of-the-art approaches and to serve as a starting point for further study in this field.
The decrease in sequencing cost and increased sophistication of assembly algorithms for short-read platforms has resulted in a sharp increase in the number of species with genome assemblies. However, ...these assemblies are highly fragmented, with many gaps, ambiguities, and errors, impeding downstream applications. We demonstrate current state of the art for de novo assembly using the domestic goat (Capra hircus) based on long reads for contig formation, short reads for consensus validation, and scaffolding by optical and chromatin interaction mapping. These combined technologies produced what is, to our knowledge, the most continuous de novo mammalian assembly to date, with chromosome-length scaffolds and only 649 gaps. Our assembly represents a ∼400-fold improvement in continuity due to properly assembled gaps, compared to the previously published C. hircus assembly, and better resolves repetitive structures longer than 1 kb, representing the largest repeat family and immune gene complex yet produced for an individual of a ruminant species.
Purpose
Incisional hernia (IH) occurs when there is a partial or complete solution of continuity of a fascia previously incised. Systematic reviews demonstrate that surgical treatment of IHs with the ...use of meshes are approximately 16%. Meta-analyses have demonstrated the superiority of mesh placement using sublay technique, but without a pathophysiological explanation. Thus, we aim to evaluate the different techniques of mesh positioning in an experimental model.
Methods
Fifty rats were distributed into five groups; control; simulation (SM)—submitted to laparotomy only; onlay—the mesh was positioned in onlay fashion; retromuscular (SL)—the mesh was positioned in a sublay fashion; intraperitoneal (IPOM)—positioning of the mesh adjacent to the transversalis fascia, inside the cavity. After 60 days, adhesions, tensiometry, histology, and immunohistochemistry were addressed.
Results
The IPOM group had the most adhesions, together with the SL group, with significantly relevant results. The SL group had higher values of tensiometric evaluation, while the IPOM group had the lowest mean in the tensiometry evaluation, being even lower than the SM group. Regarding histological and immunohistochemical findings, the SL group had a higher pixel number count compared to the groups, with statistical significance, in addition to higher expression of polymorphonuclear infiltrate and CD68 markers.
Conclusion
The mesh positioning in sublay compartment is associated with the development of more pronounce minimum tensile force required for detaching the surrounding abdominal wall tissues it was incorporated. The intensity of these findings correlates to the different histological and immunohistochemical profiles observed following each repair, since SL group was characterized by a higher proportion of collagen, inflammatory, and reparative elements. Characterizing these pro-healing elements and its counterparts will allow the development of new therapeutic tools which could be added to the still far-from-ideal current therapeutic options for IH treatment.
Background: Onychomycosis, a fungal infection of the nail bed, is responsible for up to 50% of nail disorders. Although several surveys have been conducted in different parts of the world, there have ...been no multicenter epidemiologic surveys of onychomycosis in North America. Objective: A 12-center study was undertaken to (1) determine the frequency of onychomycosis, (2) identify organisms recovered from the nails, and (3) determine the antifungal susceptibility of isolates. Methods: A total of 1832 subjects participated in this study and completed a comprehensive questionnaire, and nail clippings were collected for potassium hydroxide examination and culturing. Results: The frequency of onychomycosis, as defined by the presence of septate hyphae on direct microscopy and/or the recovery of a dermatophyte, was found to be 13.8%. In general, the dermatophyte isolates were susceptible to the antifungals tested. Conclusion: Because of the limited number of large-scale studies, the baseline incidence is not firmly established. However, the higher frequency of onychomycosis in this study may confirm the suspected increase in incidence of disease in North America. (J Am Acad Dermatol 2000;43:641-8.).
Purpose
To compare adhesion scores, repair strength and histological findings among sublay, onlay and primary repair incisional hernioplasty techniques. Surgical repairs were employed directly on ...healthy animals, without previous hernia induction, to avoid confounding factors related to hernia development.
Methods
Forty Wistar rats were divided into four groups, control, simulation, onlay and sublay. After 42 days, adhesion intensity, tensile strength of the abdominal wall and anatomopathological histological substrate were compared.
Results
SL group presented greater adhesion scores (
p
< 0.0001), higher tensiometric (
p
< 0.0001), and was characterized by more histiocytes, mononuclear cells, macrovacuolar granulomas and type I collagen on histological analysis. Pearson correlation between adhesions and tensiometry, and between tensiometry and neocollagenization showed a strong positive association (
r
= 0.8905 and 0.6757, respectively in SL group,
p
< 0.05).
Conclusion
Mesh positioning in sublay compartment was followed by increased adhesion development and provides a stronger mesh–tissue attachment, in addition, resulted in a different histological profile of the inflammation/repair substrate. The intensity of these findings was directly correlated, suggesting they could be the result of a common biological phenomenon. Our findings indicate that mesh placement following the retromuscular technique generates a superior repair response, and give clues to a better understanding of the superiority of sublay repair in achieving lower recurrence rates. Characterization of the cellular and molecular elements responsible for the superiority of this technique is in our view an essential prerequisite aiming for improvements in the therapeutic options for the treatment of this disease.
An efficient system for genetic modification and large-scale cloning of cattle is of importance for agriculture, biotechnology, and human medicine. Here, actively dividing fetal fibroblasts were ...genetically modified with a marker gene, a clonal line was selected, and the cells were fused to enucleated mature oocytes. Out of 28 embryos transferred to 11 recipient cows, three healthy, identical, transgenic calves were generated. Furthermore, the life-span of near senescent fibroblasts could be extended by nuclear transfer, as indicated by population doublings in fibroblast lines derived from a 40-day-old fetal clone. With the ability to extend the life-span of these primary cultured cells, this system would be useful for inducing complex genetic modifications in cattle
The alpaca (
) is an economically important and cultural signature species in Peru. Thus, molecular genomic information about the genes underlying the traits of interest, such as fiber properties and ...color, is critical for improved breeding and management schemes. Current knowledge about the alpaca genome, particularly the chromosomal location of such genes of interest is limited and lags far behind other livestock species. The main objective of this work was to localize alpaca candidate genes for fiber growth and color using fluorescence
hybridization (FISH). We report the mapping of candidate genes for fiber growth
,
,
,
,
, and
to chromosomes 16, 17, 4, 16, 1, and 16, respectively. Likewise, we report the mapping of candidate genes for fiber color
,
,
,
, and
to chromosomes 9, 19, 16, 1, and 14, respectively. In addition, since
clusters with five other keratin genes (
,
,
,
, and
) in scaffold 450 (Vic.Pac 2.0.2), the entire gene cluster was assigned to chromosome 16. Similarly, mapping
to chromosome 19, anchored scaffold 34 with 8 genes, viz.,
,
,
,
,
,
,
, and
to chromosome 19. These results are concordant with known conserved synteny blocks between camelids and humans, cattle and pigs.
The aim of this study was the identification of candidate genomic regions associated with fiber diameter in alpacas. DNA samples were collected from 1011 female Huacaya alpacas from two geographical ...Andean regions in Peru (Pasco and Puno), and three alpaca farms within each region. The samples were genotyped using an Affymetrix Custom Alpaca genotyping array containing 76,508 SNPs. After the quality controls, 960 samples and 51,742 SNPs were retained. Three association study methodologies were performed. The GWAS based on a linear model allowed us to identify 11 and 35 SNPs (−log10(p-values) > 4) using information on all alpacas and alpacas with extreme values of fiber diameter, respectively. The haplotype and marker analysis method allowed us to identify nine haplotypes with standardized haplotype heritability higher than six standard deviations. The selection signatures based on cross-population extended haplotype homozygosity (XP-EHH) allowed us to identify 180 SNPs with XP-EHH values greater than |3|. Four candidate regions with adjacent SNPs identified via two association methods of analysis are located on VPA6, VPA9, VPA29 and one chromosomally unassigned scaffold. This study represents the first analysis of alpaca whole genome association with fiber diameter, using a recently assembled alpaca SNP microarray.
Alpaca is a camelid species of broad economic, biological and biomedical interest, and an essential part of the cultural and historical heritage of Peru. Recently, efforts have been made to improve ...knowledge of the alpaca genome, and its genetics and cytogenetics, to develop molecular tools for selection and breeding. Here, we report cytogenetic mapping of 35 new markers to 19 alpaca autosomes and the X chromosome. Twenty-eight markers represent alpaca SNPs, of which 17 are located inside or near protein-coding genes, two are in ncRNA genes and nine are intergenic. The remaining seven markers correspond to candidate genes for fiber characteristics (
, coat color (
) and development (
). The results take the tally of cytogenetically mapped markers in alpaca to 281, covering all 36 autosomes and the sex chromosomes. The new map assignments overall agree with human-camelid conserved synteny data, except for mapping
to VPA3, suggesting a hitherto unknown homology with HSA14. The findings validate, refine and correct the current alpaca assembly
by anchoring unassigned sequence scaffolds, and ordering and orienting assigned scaffolds. The study contributes to the improvement in the alpaca reference genome and advances camelid molecular cytogenetics.
Alpacas are one of four South American Camelid species living in the highlands of the Andes. Production of alpaca fiber contributes to the economy of the region and the livelihood of many rural ...families. Fiber quantity and quality are important and in need of a modern breeding program based on genomic selection to accelerate genetic gain. To achieve this is necessary to discover enough molecular markers, single nucleotide polymorphisms (SNPs) in particular, to provide genome coverage and facilitate genome wide association studies to fiber production characteristics. The aim of this study was to discover alpaca SNPs by genotyping forty alpaca DNA samples using the BovineHD Genotyping Beadchip. Data analysis was performed with GenomeStudio (Illumina) software. Because different filters and thresholds are reported in the literature we investigated the effects of no-call threshold (≥0.05, ≥0.15, and ≥0.25) and call frequency (≥0.9 and =1.0) in identifying positive SNPs. Average GC Scores, calculated as the average of the 10% and 50% GenCall scores for each SNP (≥0.70) and the GenTrain score ≥ 0.25 parameters were applied to all comparisons. SNPs with minor allele frequency (MAF) ≥ 0.05 or ≥ 0.01 were retained. Since detection of SNPs is based on the stable binding of oligonucleotide probes to the target DNA immediately adjacent to the variant nucleotide, all positive SNP flanking sequences showing perfect alignments between the bovine and alpaca genomes for the first 21 or 26 nucleotides flanking the variant nucleotide at either side were selected. Only SNPs localized in one scaffold were assumed unique. Unique SNPs identified in both reference genomes were kept and mapped on the Vicugna_pacos 2.0.2 genome. The effects of the no-call threshold ≥ 0.25, call frequency = 1 and average GC ≥ 0.7 were meaningful and identified 6756 SNPs of which 400 were unique and polymorphic (MAF ≥ 0.01). Assignment to alpaca chromosomes was possible for 292 SNPs. Likewise, 209 SNPs were localized in 202 alpaca gene loci and 29 of these share the same loci with the dromedary. Interestingly, 69 of 400 alpaca SNPs have 100% similarity with dromedary.
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