scholarly journals Exploring complex disease gene relationships using simultaneous analysis

2014 ◽  
Author(s):  
Joseph D Romano ◽  
William G Tharp ◽  
Indra N Sarkar
Keyword(s):  
Alzheimer Disease ◽  
Phylogenetic Trees ◽  
Complex Disease ◽  
Disease Gene ◽  
Sequence Similarity ◽  
Single Gene ◽  
Genomic Data ◽  
Complex Diseases ◽  
Genetic Network ◽  
Automated Method

The characterization of complex diseases remains a great challenge for biomedical researchers due to the myriad interactions of genetic and environmental factors. Adaptation of phylogenomic techniques to increasingly available genomic data provides an evolutionary perspective that may elucidate important unknown features of complex diseases. Here an automated method is presented that leverages publicly available genomic data and phylogenomic techniques. The approach is tested with nine genes implicated in the development of Alzheimer Disease, a complex neurodegenerative syndrome. The developed technique, implemented through a suite of Ruby scripts entitled “ASAP2,” first compiles a list of sequence-similarity based orthologues using PSI-BLAST and a recursive NCBI BLAST+ search strategy, then constructs maximum parsimony phylogenetic trees for each set of nucleotide and protein sequences, and calculates phylogenetic metrics (partitioned Bremer support values, combined branch scores, and Robinson-Foulds distance) to provide an empirical assessment of evolutionary conservation within a given genetic network. This study demonstrates the potential for using automated simultaneous phylogenetic analysis to uncover previously unknown relationships among disease-associated genes that may not have been apparent using traditional, single-gene methods. Furthermore, the results provide the first integrated evolutionary history of an Alzheimer Disease gene network and identify potentially important co-evolutionary clustering around components of oxidative stress pathways.

scholarly journals Exploring complex disease gene relationships using simultaneous analysis

2014 ◽  
Author(s):  
Joseph D Romano ◽  
William G Tharp ◽  
Indra N Sarkar
Keyword(s):  
Alzheimer Disease ◽  
Phylogenetic Trees ◽  
Complex Disease ◽  
Disease Gene ◽  
Sequence Similarity ◽  
Single Gene ◽  
Genomic Data ◽  
Complex Diseases ◽  
Genetic Network ◽  
Automated Method

The characterization of complex diseases remains a great challenge for biomedical researchers due to the myriad interactions of genetic and environmental factors. Adaptation of phylogenomic techniques to increasingly available genomic data provides an evolutionary perspective that may elucidate important unknown features of complex diseases. Here an automated method is presented that leverages publicly available genomic data and phylogenomic techniques. The approach is tested with nine genes implicated in the development of Alzheimer Disease, a complex neurodegenerative syndrome. The developed technique, implemented through a suite of Ruby scripts entitled “ASAP2,” first compiles a list of sequence-similarity based orthologues using PSI-BLAST and a recursive NCBI BLAST+ search strategy, then constructs maximum parsimony phylogenetic trees for each set of nucleotide and protein sequences, and calculates phylogenetic metrics (partitioned Bremer support values, combined branch scores, and Robinson-Foulds distance) to provide an empirical assessment of evolutionary conservation within a given genetic network. This study demonstrates the potential for using automated simultaneous phylogenetic analysis to uncover previously unknown relationships among disease-associated genes that may not have been apparent using traditional, single-gene methods. Furthermore, the results provide the first integrated evolutionary history of an Alzheimer Disease gene network and identify potentially important co-evolutionary clustering around components of oxidative stress pathways.

scholarly journals Junction-skipping regulation in complex disease

2019 ◽  
Author(s):  
Ruize Liu ◽  
Juha Karjalainen ◽  
Andrea Byrnes ◽  
Beryl B. Cummings ◽  
Padhraig Gormley ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Complex Disease ◽  
Single Gene ◽  
Complex Diseases ◽  
Mrna Isoforms ◽  
Complex Disorders ◽  
Genomic Variants ◽  
Disease Associations ◽  
Human Disorders ◽  
Credible Set

AbstractMultiple mRNA isoforms can be generated from a single gene locus through alternative splicing. Abnormality in alternative splicing has been linked to many human disorders. Here using RNA-seq data from 48 tissues from GTEx v7 release and summary statistics from GWAS of complex diseases and traits, we present a study to identify genomic variants regulating junction-skipping with the goal to understand their contribution to complex diseases and traits. For each tissue, we found 48 - 575 junction-skipping events regulated by genomic variants. We performed fine-mapping on both the junction-skipping association and 23 complex disease and trait associations and mapped them to 95% credible sets. We found 13 - 279 junction-skipping regulations were mapped to a credible set with ≤5 variants. On the genome-wide scale, we noted a clear disease-tissue specificity. Results from this approach provided critical insights into the functional mechanism of the genetic disease associations and contributed to our understanding of the genetic architecture of human complex disorders.

scholarly journals Identification of Epidemiological Traits by Analysis of SARS−CoV−2 Sequences

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 764
Author(s):  
Bohu Pan ◽  
Zuowei Ji ◽  
Sugunadevi Sakkiah ◽  
Wenjing Guo ◽  
Jie Liu ◽  
...  
Keyword(s):  
Clustering Analysis ◽  
Phylogenetic Trees ◽  
Sequence Similarity ◽  
Host Age ◽  
Hierarchical Clustering Analysis ◽  
Genome Sequences ◽  
Geographic Patterns ◽  
Rapid Spread ◽  
Pairwise Sequence Similarity ◽  
Sequence Similarity Analysis

Severe acute respiratory syndrome coronavirus 2 (SARS−CoV−2) has caused the ongoing global COVID-19 pandemic that began in late December 2019. The rapid spread of SARS−CoV−2 is primarily due to person-to-person transmission. To understand the epidemiological traits of SARS−CoV−2 transmission, we conducted phylogenetic analysis on genome sequences from >54K SARS−CoV−2 cases obtained from two public databases. Hierarchical clustering analysis on geographic patterns in the resulting phylogenetic trees revealed a co-expansion tendency of the virus among neighboring countries with diverse sources and transmission routes for SARS−CoV−2. Pairwise sequence similarity analysis demonstrated that SARS−CoV−2 is transmitted locally and evolves during transmission. However, no significant differences were seen among SARS−CoV−2 genomes grouped by host age or sex. Here, our identified epidemiological traits provide information to better prevent transmission of SARS−CoV−2 and to facilitate the development of effective vaccines and therapeutics against the virus.

scholarly journals Amphritea ceti sp. nov., isolated from faeces of Beluga whale (Delphinapterus leucas)

2014 ◽  
Vol 64 (Pt_12) ◽  
pp. 4068-4072 ◽  
Author(s):  
Young-Ok Kim ◽  
Sooyeon Park ◽  
Doo Nam Kim ◽  
Bo-Hye Nam ◽  
Sung-Min Won ◽  
...  
Keyword(s):  
Phylogenetic Trees ◽  
Sequence Similarity ◽  
Beluga Whale ◽  
Delphinapterus Leucas ◽  
Rrna Gene ◽  
Phenotypic Properties ◽  
Content Type ◽  
Link Type ◽  
Beluga Whale Delphinapterus Leucas ◽  
Type Strains

A Gram-stain-negative, aerobic, non-spore-forming, non-flagellated and rod-shaped or ovoid bacterial strain, designated RA1T, was isolated from faeces collected from Beluga whale (Delphinapterus leucas) in Yeosu aquarium, South Korea. Strain RA1T grew optimally at 25 °C, at pH 7.0–8.0 and in the presence of 2.0 % (w/v) NaCl. Neighbour-joining, maximum-likelihood and maximum-parsimony phylogenetic trees based on 16S rRNA gene sequences revealed that strain RA1T joins the cluster comprising the type strains of three species of the genus Amphritea , with which it exhibited 95.8–96.0 % sequence similarity. Sequence similarities to the type strains of other recognized species were less than 94.3 %. Strain RA1T contained Q-8 as the predominant ubiquinone and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C18 : 1ω7c and C16 : 0 as the major fatty acids. The major polar lipids of strain RA1T were phosphatidylethanolamine, phosphatidylglycerol, two unidentified lipids and one unidentified aminolipid. The DNA G+C content of strain RA1T was 47.4 mol%. The differential phenotypic properties, together with the phylogenetic distinctiveness, revealed that strain RA1T is separated from other species of the genus Amphritea . On the basis of the data presented, strain RA1T is considered to represent a novel species of the genus Amphritea , for which the name Amphritea ceti sp. nov. is proposed. The type strain is RA1T ( = KCTC 42154T = NBRC 110551T).

scholarly journals Pseudoseohaeicola caenipelagi gen. nov., sp. nov., isolated from a tidal flat

2015 ◽  
Vol 65 (Pt_6) ◽  
pp. 1819-1824 ◽  
Author(s):  
Sooyeon Park ◽  
Ji-Min Park ◽  
Chul-Hyung Kang ◽  
Song-Gun Kim ◽  
Jung-Hoon Yoon
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Tidal Flat ◽  
Type Strain ◽  
Type Species ◽  
Phylogenetic Trees ◽  
Sequence Similarity ◽  
Rrna Gene ◽  
Content Type ◽  
Link Type

A Gram-stain-negative, non-motile, aerobic and pleomorphic bacterium, designated BS-W13T, was isolated from a tidal flat on the South Sea, South Korea, and its taxonomic position was investigated using a polyphasic approach. Strain BS-W13T grew optimally at 25 °C, at pH 7.0–8.0 and in the presence of 1.0–2.0 % (w/v) NaCl. Neighbour-joining and maximum-parsimony phylogenetic trees based on 16S rRNA gene sequences showed that strain BS-W13T clustered with the type strain of Seohaeicola saemankumensis , showing the highest sequence similarity (95.96 %) to this strain. Strain BS-W13T exhibited 16S rRNA gene sequence similarity values of 95.95, 95.91, 95.72 and 95.68 % to the type strains of Sulfitobacter donghicola , Sulfitobacter porphyrae , Sulfitobacter mediterraneus and Roseobacter litoralis , respectively. Strain BS-W13T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c as the major fatty acid. The polar lipid profile of strain BS-W13T, containing phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, one unidentified aminolipid and one unidentified lipid as major components, was distinguishable from those of some phylogenetically related taxa. The DNA G+C content of strain BS-W13T was 58.1 mol%. The phylogenetic data and differential chemotaxonomic and other phenotypic properties revealed that strain BS-W13T constitutes a novel genus and species within family Rhodobacteraceae of the class Alphaproteobacteria , for which the name Pseudoseohaeicola caenipelagi gen. nov., sp. nov. is proposed. The type strain is BS-W13T ( = KCTC 42349T = CECT 8724T).

scholarly journals Belliella aquatica sp. nov., isolated from a saline lake

2015 ◽  
Vol 65 (Pt_5) ◽  
pp. 1622-1627 ◽  
Author(s):  
Zhi-Ping Zhong ◽  
Ying Liu ◽  
Ting-Ting Hou ◽  
Yu-Guang Zhou ◽  
Hong-Can Liu ◽  
...  
Keyword(s):  
Type Species ◽  
Phylogenetic Trees ◽  
Saline Lake ◽  
Qaidam Basin ◽  
Sequence Similarity ◽  
Rrna Gene ◽  
Respiratory Quinone ◽  
Content Type ◽  
Link Type ◽  
Gram Staining

A Gram-staining-negative bacterium, strain TS-T86T, was isolated from Lake Tuosu, a saline lake (salinity 5.4 %, w/w) in Qaidam basin, China. Its taxonomic position was determined by using a polyphasic approach. Strain TS-T86T was strictly heterotrophic, aerobic and catalase- and oxidase-positive. Cells were non-spore-forming, non-motile rods, 0.4–0.6 µm wide and 1.2–2.3 µm long. Growth was observed in the presence of 0–9.0 % (w/v) NaCl (optimum, 2.0 %), at 4–35 °C (optimum, 25 °C) and at pH 7.0–10.5 (optimum, pH 8.5–9.0). Strain TS-T86T contained MK-7 as the predominant respiratory quinone. The major fatty acids (>10 %) were iso-C15 : 1 G, iso-C15 : 0, iso-C17 : 1ω9c, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The polar lipids consisted of phosphatidylethanolamine, an unknown phospholipid, six unidentified aminolipids and two uncharacterized lipids. The DNA G+C content was 35 mol% (T m). Phylogenetic trees based on 16S rRNA gene sequences showed that strain TS-T86T was associated with the genus Belliella , and showed the highest sequence similarity to Belliella baltica BA134T (98.5 %) and then to Belliella kenyensis No.164T (95.7 %) and Belliella pelovolcani CC-SAL-25T (95.3 %). DNA–DNA relatedness of strain TS-T86T to Belliella baltica DSM 15883T was 32±3 %. It is concluded that strain TS-T86T represents a novel species of the genus Belliella , for which the name Belliella aquatica sp. nov. is proposed. The type strain is TS-T86T ( = CGMCC 1.12479T = JCM 19468T).

scholarly journals Assessing universality of DNA barcoding in geographically isolated selected desert medicinal species of Fabaceae and Poaceae

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4499 ◽  
Author(s):  
Aisha Tahir ◽  
Fatma Hussain ◽  
Nisar Ahmed ◽  
Abdolbaset Ghorbani ◽  
Amer Jamil
Keyword(s):  
Dna Barcoding ◽  
Species Identification ◽  
Phylogenetic Trees ◽  
Sequence Similarity ◽  
Sequence Divergence ◽  
Species Level ◽  
Practical Implementation ◽  
Medicinal Species ◽  
Level Identification ◽  
Geographically Isolated

In pursuit of developing fast and accurate species-level molecular identification methods, we tested six DNA barcodes, namely ITS2, matK, rbcLa, ITS2+matK, ITS2+rbcLa, matK+rbcLa and ITS2+matK+rbcLa, for their capacity to identify frequently consumed but geographically isolated medicinal species of Fabaceae and Poaceae indigenous to the desert of Cholistan. Data were analysed by BLASTn sequence similarity, pairwise sequence divergence in TAXONDNA, and phylogenetic (neighbour-joining and maximum-likelihood trees) methods. Comparison of six barcode regions showed that ITS2 has the highest number of variable sites (209/360) for tested Fabaceae and (106/365) Poaceae species, the highest species-level identification (40%) in BLASTn procedure, distinct DNA barcoding gap, 100% correct species identification in BM and BCM functions of TAXONDNA, and clear cladding pattern with high nodal support in phylogenetic trees in both families. ITS2+matK+rbcLa followed ITS2 in its species-level identification capacity. The study was concluded with advocating the DNA barcoding as an effective tool for species identification and ITS2 as the best barcode region in identifying medicinal species of Fabaceae and Poaceae. Current research has practical implementation potential in the fields of pharmaco-vigilance, trade of medicinal plants and biodiversity conservation.

scholarly journals A New Subclade of Leptosphaeria biglobosa Identified from Brassica rapa

2019 ◽  
Vol 20 (7) ◽  
pp. 1668 ◽  
Author(s):  
Zhongwei Zou ◽  
Xuehua Zhang ◽  
Paula Parks ◽  
Lindsey du Toit ◽  
Angela Van de Wouw ◽  
...  
Keyword(s):  
Brassica Rapa ◽  
Phylogenetic Trees ◽  
Single Gene ◽  
Leptosphaeria Maculans ◽  
Stem Canker ◽  
Willamette Valley ◽  
Gene Sequences ◽  
Distance Analysis ◽  
Pathogenicity Tests ◽  
Leptosphaeria Biglobosa

Blackleg (Phoma stem canker) of crucifers is a globally important disease caused by the ascomycete species complex comprising of Leptosphaeria maculans and Leptosphaeria biglobosa. Six blackleg isolates recovered from Brassica rapa cv. Mizspoona in the Willamette Valley of Oregon were characterized as L. biglobosa based on standard pathogenicity tests and molecular phylogenetic analysis. These isolates were compared to 88 characterized L. biglobosa isolates from western Canada, 22 isolates from Australia, and 6 L. maculans isolates from Idaho, USA using maximum parsimony and distance analysis of phylogenetic trees generated from the ITS rDNA (internal transcribed spacer rDNA) sequence, and the actin and β-tubulin gene sequences. The L. biglobosa isolates derived from B. rapa collected in Oregon formed a separate subclade based on concatenated gene sequences or a single gene sequence, regardless of the analyses. Pathogenicity tests showed that these isolates failed to infect either resistant or susceptible B. napus cultivars, but caused severe symptoms on three B. rapa cultivars (Accession number: UM1113, UM1112, and UM1161), a B. oleracea var. capitata (cabbage) cultivar (Copenhagen Market), and two B. juncea cultivars (CBM, a common brown Mustard, and Forge). These findings demonstrated that the L. biglobosa isolates derived from a B. rapa crop in Oregon were genetically distinct from existing species of L. biglobosa, and constitute a new subclade, herein proposed as L. biglobosa ‘americensis’.

scholarly journals Deconstruction of Vulnerability to Complex Diseases: Enhanced Effect Sizes and Power of Intermediate Phenotypes

2007 ◽  
Vol 7 ◽  
pp. 124-130 ◽  
Author(s):  
David Goldman ◽  
Francesca Ducci
Keyword(s):  
Effect Size ◽  
Complex Disease ◽  
Complex Diseases ◽  
Effect Sizes ◽  
Complex Disorders ◽  
Large Samples ◽  
Intermediate Phenotypes ◽  
Genome Association ◽  
Whole Genome Association ◽  
Disease Loci

The deconstruction of vulnerability to complex disease with the help of intermediate phenotypes, including the heritable and disease-associated endophenotypes, is a legacy of Henri Begleiter. Systematic searches for genes influencing complex disorders, including bipolar disorder, have recently been completed using whole genome association (WGA), identifying a series of validated loci. Using this information, it is possible to compare effect sizes of disease loci discovered in very large samples to the effect sizes of replicated functional loci determining intermediate phenotypes that are of essential interest in psychiatric disorders. It is shown that the genes influencing intermediate phenotypes tend to have a larger effect size. Furthermore, the WGA results reveal that the number of loci of large effect size for complex diseases is limited, and yet multiple functional loci have already been identified for intermediate phenotypes relevant to psychiatric diseases, and without the benefit of WGA.

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