scholarly journals Prediction of lithium response using genomic data

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
William Stone ◽  
Abraham Nunes ◽  
Kazufumi Akiyama ◽  
Nirmala Akula ◽  
Raffaella Ardau ◽  
...  
Keyword(s):  
Cross Validation ◽  
Genomic Data ◽  
Postsynaptic Membrane ◽  
Classification Performance ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genomic Dataset ◽  
Task Classification ◽  
Lithium Response

AbstractPredicting lithium response prior to treatment could both expedite therapy and avoid exposure to side effects. Since lithium responsiveness may be heritable, its predictability based on genomic data is of interest. We thus evaluate the degree to which lithium response can be predicted with a machine learning (ML) approach using genomic data. Using the largest existing genomic dataset in the lithium response literature (n = 2210 across 14 international sites; 29% responders), we evaluated the degree to which lithium response could be predicted based on 47,465 genotyped single nucleotide polymorphisms using a supervised ML approach. Under appropriate cross-validation procedures, lithium response could be predicted to above-chance levels in two constituent sites (Halifax, Cohen’s kappa 0.15, 95% confidence interval, CI [0.07, 0.24]; and Würzburg, kappa 0.2 [0.1, 0.3]). Variants with shared importance in these models showed over-representation of postsynaptic membrane related genes. Lithium response was not predictable in the pooled dataset (kappa 0.02 [− 0.01, 0.04]), although non-trivial performance was achieved within a restricted dataset including only those patients followed prospectively (kappa 0.09 [0.04, 0.14]). Genomic classification of lithium response remains a promising but difficult task. Classification performance could potentially be improved by further harmonization of data collection procedures.

Classification of wheat PPO genes and effect of non-synonymous cSNP on kernel PPO activity

2008 ◽  
Vol 5 (1) ◽  
pp. 81-86 ◽  
Author(s):  
Wang Xiao-Bo ◽  
Ma Chuan-Xi ◽  
Si Hong-Qi ◽  
He Xian-Fang
Keyword(s):  
Nucleotide Polymorphisms ◽  
Coding Region ◽  
Chain Reaction ◽  
Wheat Varieties ◽  
Single Nucleotide ◽  
Pcr Product ◽  
Dnaman Software ◽  
Dna Fragment ◽  
Polymerase Chain

AbstractPolyphenol oxidase (PPO) activity is highly related to the undesirable browning of wheat-based end products. In this study, wheat PPO sequences (mRNA) were searched/BLASTed in the NCBI database and aligned using DNAMAN software. The results showed that wheat PPO genes could be divided into two clusters (I and II) and that three genes (‘i’) of cluster II seemed not to be located on chromosomes 2A and 2D. Ninety-four single nucleotide polymorphisms (SNPs) were detected between two haplotypes of the PPO gene on chromosome 2D. Eighty of these were found in the coding region (coding (c) SNPs) and 36 were non-synonymous cSNPs, which could affect the PPO amino acid sequence. Primers (STS-H) were designed at some non-synonymous cSNPs sites and were used to investigate the correlations between allelic variants and PPO activity of seeds – a total of 130 common wheat varieties were evaluated in 2 years. The results showed that STS-H could amplify a 460 bp DNA fragment in most cultivars with high PPO activity, while no PCR product was detected in most cultivars with low PPO activity. To improve the selection efficiency of a single dominance molecular marker, the multiplex polymerase chain reaction (PCR) system of STS-H and STS01 markers was also studied, based on the complementary between them.

scholarly journals Re-Identification of Individuals in Genomic Data-Sharing Beacons via Allele Inference

2017 ◽  
Author(s):  
Nora von Thenen ◽  
Erman Ayday ◽  
A. Ercument Cicek
Keyword(s):  
Data Sharing ◽  
Genomic Data ◽  
Nucleotide Polymorphisms ◽  
Privacy Risk ◽  
High Confidence ◽  
Single Nucleotide ◽  
Order Markov Chain ◽  
Adversary Model ◽  
Very High ◽  
Membership Information

AbstractGenomic datasets are often associated with sensitive phenotypes. Therefore, the leak of membership information is a major privacy risk. Genomic beacons aim to provide a secure, easy to implement, and standardized interface for data sharing by only allowing yes/no queries on the presence of specific alleles in the dataset. Previously deemed secure against re-identification attacks, beacons were shown to be vulnerable despite their stringent policy. Recent studies have demonstrated that it is possible to determine whether the victim is in the dataset, by repeatedly querying the beacon for his/her single nucleotide polymorphisms (SNPs). In this work, we propose a novel re-identification attack and show that the privacy risk is more serious than previously thought. Using the proposed attack, even if the victim systematically hides informative SNPs (i.e., SNPs with very low minor allele frequency -MAF-), it is possible to infer the alleles at positions of interest as well as the beacon query results with very high confidence. Our method is based on the fact that alleles at different loci are not necessarily independent. We use the linkage disequilibrium and a high-order Markov chain-based algorithm for the inference. We show that in a simulated beacon with 65 individuals from the CEU population, we can infer membership of individuals with 95% confidence with only 5 queries, even when SNPs with MAF less than 0.05 are hidden. This means, we need less than 0.5% of the number of queries that existing works require, to determine beacon membership under the same conditions. We further show that countermeasures such as hiding certain parts of the genome or setting a query budget for the user would fail to protect the privacy of the participants under our adversary model.

scholarly journals Whole genome sequencing and phylogenetic classification of Tunisian SARS-CoV-2 strains from patients of the Military Hospital in Tunis

Virus Genes ◽  
2020 ◽  
Vol 56 (6) ◽  
pp. 767-771 ◽  
Author(s):  
Susann Handrick ◽  
Malena Bestehorn-Willmann ◽  
Simone Eckstein ◽  
Mathias C. Walter ◽  
Markus H. Antwerpen ◽  
...  
Keyword(s):  
Nasal Swab ◽  
Middle Eastern ◽  
Military Hospital ◽  
Nucleotide Polymorphisms ◽  
African Region ◽  
Single Nucleotide ◽  
Virus Genomes ◽  
The Military ◽  
Tunisian Family

AbstractIn the present work, two complete genome sequences of SARS-CoV-2 were obtained from nasal swab samples of Tunisian SARS-CoV-2 PCR-positive patients using nanopore sequencing. The virus genomes of two of the patients examined, a Tunisian soldier returning from a mission in Morocco and a member of another Tunisian family, showed significant differences in analyses of the total genome and single nucleotide polymorphisms (SNPs). Phylogenetic relationships with known SARS-CoV-2 genomes in the African region, some European and Middle Eastern countries and initial epidemiological conclusions indicate that the introduction of SARS-CoV-2 into Tunisia from two independent sources was travel-related.

scholarly journals Classification of small ruminant lentivirus subtype A2, subgroups 1 and 2 based on whole genome comparisons and complex recombination patterns

F1000Research ◽  
2021 ◽  
Vol 9 ◽  
pp. 1449
Author(s):  
Aaron M. Dickey ◽  
Timothy P. L. Smith ◽  
Michael L. Clawson ◽  
Michael P. Heaton ◽  
Aspen M. Workman
Keyword(s):  
Small Ruminant ◽  
Transmembrane Protein ◽  
Full Length ◽  
Nucleotide Polymorphisms ◽  
Wasting Disease ◽  
Single Nucleotide ◽  
Viral Genomes ◽  
Haplotype 1 ◽  
Genome Scale

Background: Small ruminant lentiviruses (SRLVs) cause a multisystemic chronic wasting disease in sheep across much of the world. SRLV subtype A2 is prevalent in North America and further classified into multiple subgroups based on variation in the group antigens gene (gag) and envelope (env) genes. In sheep, the ovine transmembrane protein 154 (TMEM154) gene is associated with SRLV susceptibility. Ewes with at least one copy of TMEM154 encoding a full-length protein with glutamate at position 35 (E35; haplotypes 2 and 3), are highly susceptible to SRLV infection while ewes with any combination of TMEM154 haplotypes which encodes lysine (K35; haplotype 1), or truncated proteins (haplotypes 4 and 6) are several times less so. A2 subgroups 1 and 2 are associated with host TMEM154 genotypes; subgroup 1 with the K35/K35 genotype and subgroup 2 with the E35/E35 genotype. Methods:  Sequence variation within and among full-length assemblies of SRLV subtype A2 subgroups 1 and 2 was analyzed to identify genome-scale recombination patterns and subgroup-specific variants. Results:  Consensus viral genomes were assembled from 23 infected sheep, including animals of assorted TMEM154 genotypes comprised of haplotypes 1, 2, or 3. Viral genome analysis identified viral subgroups 1 and 2 among the samples, and revealed additional sub-structure within subgroup 2 based on models predicting complex patterns of recombination between the two subgroups in several genomes. Animals with evidence of dual subgroup infection also possessed the most diverse quasi-species and the most highly recombined consensus genomes. After accounting for recombination, 413 subgroup diagnostic single nucleotide polymorphisms (SNPs) were identified. Conclusions:  The viral subgroup framework developed to classify SRLV consensus genomes along a continuum of recombination suggests that animals with the TMEM154 E35/K35 genotype may represent a reservoir for producing viral genomes representing recombination between A2 subgroups 1 and 2.

scholarly journals A new nomenclature for the livestock-associated Mycobacterium tuberculosis complex based on phylogenomics

2021 ◽  
Vol 1 ◽  
pp. 100
Author(s):  
Michaela Zwyer ◽  
Cengiz Çavusoglu ◽  
Giovanni Ghielmetti ◽  
Maria Lodovica Pacciarini ◽  
Erika Scaltriti ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Mycobacterium Tuberculosis ◽  
Epidemiological Studies ◽  
Nucleotide Polymorphisms ◽  
Phylogenetic Groups ◽  
Single Nucleotide ◽  
Phylogenetic Lineages ◽  
Made In

Background The bacteria that compose the Mycobacterium tuberculosis complex (MTBC) cause tuberculosis (TB) in humans and in different animals, including livestock. Much progress has been made in understanding the population structure of the human-adapted members of the MTBC by combining phylogenetics with genomics. Accompanying the discovery of new genetic diversity, a body of operational nomenclature has evolved to assist comparative and molecular epidemiological studies of human TB. By contrast, for the livestock-associated MTBC members, Mycobacterium bovis, M. caprae and M. orygis, there has been a lack of comprehensive nomenclature to accommodate new genetic diversity uncovered by emerging phylogenomic studies. We propose to fill this gap by putting forward a new nomenclature covering the main phylogenetic groups within M. bovis, M. caprae and M. orygis. Methods We gathered a total of 8,736 whole-genome sequences (WGS) from public sources and 39 newly sequenced strains, and selected a subset of 829 WGS, representative of the worldwide diversity of M. bovis, M. caprae and M. orygis. We used phylogenetics and genetic diversity patterns inferred from WGS to define groups. Results We propose to divide M. bovis, M. caprae and M. orygis in three main phylogenetic lineages, which we named La1, La2 and La3, respectively. Within La1, we identified several monophyletic groups, which we propose to classify into eight sublineages (La1.1-La1.8). These sublineages differed in geographic distribution, with some being geographically restricted and others globally widespread, suggesting different expansion abilities. To ease molecular characterization of these MTBC groups by the community, we provide phylogenetically informed, single nucleotide polymorphisms that can be used as barcodes for genotyping. These markers were implemented in KvarQ and TB-Profiler, which are platform-independent, open-source tools. Conclusions Our results contribute to an improved classification of the genetic diversity within the livestock-associated MTBC, which will benefit future molecular epidemiological and evolutionary studies.

scholarly journals The Diagnosis of Asthma using Hilbert-Huang Transform and Deep Learning on Lung Sounds

2019 ◽  
pp. 100-105
Author(s):  
Gokhan Altan ◽  
Yakup Kutlu ◽  
Adnan Ozhan Pekmezci ◽  
Serkan Nural
Keyword(s):  
Healthy Subjects ◽  
Cross Validation ◽  
Classification Performance ◽  
Lung Sounds ◽  
Deep Belief Networks ◽  
Intrinsic Mode Functions ◽  
Hilbert Huang Transform ◽  
Sensitivity And Selectivity ◽  
Fold Cross Validation

Lung auscultation is the most effective and indispensable method for diagnosing various respiratory disorders by using the sounds from the airways during inspirium and exhalation using a stethoscope. In this study, the statistical features are calculated from intrinsic mode functions that are extracted by applying the Hilbert-Huang Transform to the lung sounds from 12 different auscultation regions on the chest and back. The classification of the lung sounds from asthma and healthy subjects is performed using Deep Belief Networks (DBN). The DBN classifier model with two hidden layers has been tested using 5-fold cross validation method. The proposed DBN separated lung sounds from asthmatic and healthy subjects with high classification performance rates of 84.61%, 85.83%, and 77.11% for overall accuracy, sensitivity, and selectivity, respectively using frequencytime analysis.

scholarly journals PrP genotypes of atypical scrapie cases in Great Britain

2006 ◽  
Vol 87 (11) ◽  
pp. 3141-3149 ◽  
Author(s):  
G. C. Saunders ◽  
S. Cawthraw ◽  
S. J. Mountjoy ◽  
J. Hope ◽  
O. Windl
Keyword(s):  
Great Britain ◽  
Amino Acid Position ◽  
Classical Scrapie ◽  
Atypical Scrapie ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Scrapie Infection ◽  
Prp Gene ◽  
Phenylalanine Residue

Great Britain and elsewhere have detected atypical scrapie infection in sheep with PrP genotypes thought to be genetically resistant to the classical form of scrapie. DNA sequencing of the PrP gene of British atypical scrapie cases (n=69), classical scrapie cases (n=59) and scrapie-free controls (n=138) was undertaken to identify whether PrP variants, other than the three well-characterized polymorphic codons, influenced susceptibility to atypical scrapie infection. Four non-synonymous changes, M112T, M137T, L141F and P241S, were detected that are most probably associated with the A136R154Q171 haplotype. Only the PrP variant containing a phenylalanine residue at amino acid position 141 was found to be associated more commonly with the atypical scrapie cases. In addition to the single nucleotide polymorphisms associated with the ARQ allele, two out of nine atypical scrapie cases with the ARR/ARR genotype were found to contain a 24 bp insertion, leading to an additional octapeptide repeat. In terms of PrP genetics, one classification of the GB scrapie cases examined in this study would place animals carrying any homozygous or heterozygous combination of ARR, AHQ or AF141RQ alleles, or any one of these alleles when paired with ARQ, as being susceptible to atypical scrapie infection, and animals heterozygous or homozygous for VRQ or homozygous for ARQ as being susceptible to classical scrapie disease. The AHQ PrP allele was associated with the highest incidence of atypical scrapie (263 per 100 000 alleles), whilst VRQ was associated with the lowest incidence (10 per 100 000 alleles).

scholarly journals Sequence diversity of the mucABD locus in Pseudomonas aeruginosa isolates from patients with cystic fibrosis

Microbiology ◽  
2006 ◽  
Vol 152 (11) ◽  
pp. 3261-3269 ◽  
Author(s):  
Alessandra Bragonzi ◽  
Lutz Wiehlmann ◽  
Jens Klockgether ◽  
Nina Cramer ◽  
Dieter Worlitzsch ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
De Novo ◽  
Nucleotide Polymorphisms ◽  
Aquatic Habitats ◽  
Environmental Isolates ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Airway Colonization

The mucA gene of the muc operon, which is instrumental in the control of the biosynthesis of the exopolysaccharide alginate, is a hotspot of mutation in Pseudomonas aeruginosa, a micro-organism that chronically colonizes the airways of individuals with cystic fibrosis (CF). The mucA, mucB and mucD genes were sequenced in nine environmental isolates from aquatic habitats, and in 37 P. aeruginosa strains isolated from 10 patients with CF, at onset or at a late stage of chronic airway colonization, in order to elucidate whether there was any association between mutation and background genotype. The 61 identified single nucleotide polymorphisms (SNPs) segregated into 18 mucABD genotypes. Acquired and de novo stop mucA mutations were present in 14 isolates (38 %) of five mucABD genotypes. ΔG430 was the most frequent and recurrent mucA mutation detected in four genotypes. The classification of strains by mucABD genotype was generally concordant with that by genome-wide SpeI fragment pattern or multilocus SNP genotypes. The exceptions point to intragenic mosaicism and interclonal recombination as major forces for intraclonal evolution at the mucABD locus.

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