Identifying consensus disease pathways in Parkinson's disease using an integrative systems biology approach
Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both G...
Gespeichert in:
| Veröffentlicht in: | PloS one 2011-02, Vol.6 (2), p.e16917-e16917 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e16917 |
|---|---|
| container_issue | 2 |
| container_start_page | e16917 |
| container_title | PloS one |
| container_volume | 6 |
| creator | Edwards, Yvonne J K Beecham, Gary W Scott, William K Khuri, Sawsan Bademci, Guney Tekin, Demet Martin, Eden R Jiang, Zhijie Mash, Deborah C ffrench-Mullen, Jarlath Pericak-Vance, Margaret A Tsinoremas, Nicholas Vance, Jeffery M |
| description | Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both GWAS and gene expression. The top 5000 SNPs (p |
| doi_str_mv | 10.1371/journal.pone.0016917 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1312178170</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A476904252</galeid><doaj_id>oai_doaj_org_article_f96b411d697d45b49c5381c4385fc70e</doaj_id><sourcerecordid>A476904252</sourcerecordid><originalsourceid>FETCH-LOGICAL-c691t-664aca172cc72d3f664c6bccf9c91f5659a25fdeec9f3c2a84be527b8204bdde3</originalsourceid><addsrcrecordid>eNqNk0tv1DAUhSMEoqXwDxBEQqJiMYNfccYbpKriMVKlIl5by3GcjKcZO_V1CvPv8TBpmaAuUBZJfL9zbnzim2XPMZpjWuK3az8Ep7p5752ZI4S5wOWD7BgLSmacIPrw4PkoewKwRqigC84fZ0cEU85EQY6zq2VtXLTN1ro2196BcTBAXlswCkzeq7j6qbaQW5d_VuHKOvDu9G99gJ1OuVSPpg0q2huTwxai2UBeWd_5dpurvg9e6dXT7FGjOjDPxvtJ9v3D-2_nn2YXlx-X52cXM532EGecM6UVLonWJalpk941r7RuhBa4KXghFCma2hgtGqqJWrDKFKSsFgSxqq4NPcle7n37zoMccwKJKSa4XOASJWK5J2qv1rIPdqPCVnpl5Z8FH1qpQrS6M7IRvGIY11yUNSsqJnQKEWtGF0WjS7Tr9m7sNlQbU-sUZ1DdxHRacXYlW38jKWIUCZYMTkeD4K8HA1FuLGjTdcoZP4BcFAVBKKGJfPUPef_mRqpV6futa3xqq3ee8oyVXCBGCpKo-T1UumqzsekgmMam9YngzUSQmGh-xVYNAHL59cv_s5c_puzrA3ZlVBdX4Lsh2nQapyDbgzp4gGCau4wxkruRuE1D7kZCjiORZC8O_8-d6HYG6G82egi1</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1312178170</pqid></control><display><type>article</type><title>Identifying consensus disease pathways in Parkinson's disease using an integrative systems biology approach</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>EZB Free E-Journals</source><source>DOAJ Directory of Open Access Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Edwards, Yvonne J K ; Beecham, Gary W ; Scott, William K ; Khuri, Sawsan ; Bademci, Guney ; Tekin, Demet ; Martin, Eden R ; Jiang, Zhijie ; Mash, Deborah C ; ffrench-Mullen, Jarlath ; Pericak-Vance, Margaret A ; Tsinoremas, Nicholas ; Vance, Jeffery M</creator><creatorcontrib>Edwards, Yvonne J K ; Beecham, Gary W ; Scott, William K ; Khuri, Sawsan ; Bademci, Guney ; Tekin, Demet ; Martin, Eden R ; Jiang, Zhijie ; Mash, Deborah C ; ffrench-Mullen, Jarlath ; Pericak-Vance, Margaret A ; Tsinoremas, Nicholas ; Vance, Jeffery M</creatorcontrib><description>Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both GWAS and gene expression. The top 5000 SNPs (p<0.01) from a joint analysis of three existing PD GWAS were identified and each assigned to a gene. For gene expression, rather than the traditional comparison of one anatomical region between sets of patients and controls, we identified differentially expressed genes between adjacent Braak regions in each individual and adjusted using average control expression profiles. Over-represented pathways were calculated using a hyper-geometric statistical comparison. An integrated, systems meta-analysis of the over-represented pathways combined the expression and GWAS results using a Fisher's combined probability test. Four of the top seven pathways from each approach were identical. The top three pathways in the meta-analysis, with their corrected p-values, were axonal guidance (p = 2.8E-07), focal adhesion (p = 7.7E-06) and calcium signaling (p = 2.9E-05). These results support that a systems biology (pathway) approach will provide additional insight into the genetic etiology of PD and that these pathways have both biological and statistical support to be important in PD.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0016917</identifier><identifier>PMID: 21364952</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Analysis ; Axon guidance ; Bioinformatics ; Biological effects ; Biology ; Brain ; Calcium ; Calcium signalling ; Chromosome Mapping - methods ; Chromosome Mapping - statistics & numerical data ; Consensus ; Encyclopedias ; Etiology ; Gene expression ; Gene Expression Profiling - methods ; Gene Expression Profiling - statistics & numerical data ; Gene Regulatory Networks ; Genes ; Genetic Predisposition to Disease ; Genetic research ; Genome-wide association studies ; Genome-Wide Association Study - methods ; Genome-Wide Association Study - statistics & numerical data ; Genomes ; Genomics ; Humans ; Insects ; Kinases ; MAP Kinase Signaling System - genetics ; MAP Kinase Signaling System - physiology ; Mathematics ; Medical research ; Medicine ; Meta-analysis ; Metabolic Networks and Pathways - genetics ; Models, Biological ; Movement disorders ; Neurodegenerative diseases ; Parkinson Disease - genetics ; Parkinson's disease ; Parkinsons disease ; Pathogenesis ; Pathology ; Pathways ; Polymorphism, Single Nucleotide ; Receptor Cross-Talk - physiology ; Signal Transduction - genetics ; Signal Transduction - physiology ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Statistical analysis ; Statistics ; Studies ; Systems Biology - methods ; Systems Integration</subject><ispartof>PloS one, 2011-02, Vol.6 (2), p.e16917-e16917</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Edwards et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Edwards et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-664aca172cc72d3f664c6bccf9c91f5659a25fdeec9f3c2a84be527b8204bdde3</citedby><cites>FETCH-LOGICAL-c691t-664aca172cc72d3f664c6bccf9c91f5659a25fdeec9f3c2a84be527b8204bdde3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3043094/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3043094/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21364952$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Edwards, Yvonne J K</creatorcontrib><creatorcontrib>Beecham, Gary W</creatorcontrib><creatorcontrib>Scott, William K</creatorcontrib><creatorcontrib>Khuri, Sawsan</creatorcontrib><creatorcontrib>Bademci, Guney</creatorcontrib><creatorcontrib>Tekin, Demet</creatorcontrib><creatorcontrib>Martin, Eden R</creatorcontrib><creatorcontrib>Jiang, Zhijie</creatorcontrib><creatorcontrib>Mash, Deborah C</creatorcontrib><creatorcontrib>ffrench-Mullen, Jarlath</creatorcontrib><creatorcontrib>Pericak-Vance, Margaret A</creatorcontrib><creatorcontrib>Tsinoremas, Nicholas</creatorcontrib><creatorcontrib>Vance, Jeffery M</creatorcontrib><title>Identifying consensus disease pathways in Parkinson's disease using an integrative systems biology approach</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both GWAS and gene expression. The top 5000 SNPs (p<0.01) from a joint analysis of three existing PD GWAS were identified and each assigned to a gene. For gene expression, rather than the traditional comparison of one anatomical region between sets of patients and controls, we identified differentially expressed genes between adjacent Braak regions in each individual and adjusted using average control expression profiles. Over-represented pathways were calculated using a hyper-geometric statistical comparison. An integrated, systems meta-analysis of the over-represented pathways combined the expression and GWAS results using a Fisher's combined probability test. Four of the top seven pathways from each approach were identical. The top three pathways in the meta-analysis, with their corrected p-values, were axonal guidance (p = 2.8E-07), focal adhesion (p = 7.7E-06) and calcium signaling (p = 2.9E-05). These results support that a systems biology (pathway) approach will provide additional insight into the genetic etiology of PD and that these pathways have both biological and statistical support to be important in PD.</description><subject>Acids</subject><subject>Analysis</subject><subject>Axon guidance</subject><subject>Bioinformatics</subject><subject>Biological effects</subject><subject>Biology</subject><subject>Brain</subject><subject>Calcium</subject><subject>Calcium signalling</subject><subject>Chromosome Mapping - methods</subject><subject>Chromosome Mapping - statistics & numerical data</subject><subject>Consensus</subject><subject>Encyclopedias</subject><subject>Etiology</subject><subject>Gene expression</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Profiling - statistics & numerical data</subject><subject>Gene Regulatory Networks</subject><subject>Genes</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic research</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genome-Wide Association Study - statistics & numerical data</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Humans</subject><subject>Insects</subject><subject>Kinases</subject><subject>MAP Kinase Signaling System - genetics</subject><subject>MAP Kinase Signaling System - physiology</subject><subject>Mathematics</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Meta-analysis</subject><subject>Metabolic Networks and Pathways - genetics</subject><subject>Models, Biological</subject><subject>Movement disorders</subject><subject>Neurodegenerative diseases</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson's disease</subject><subject>Parkinsons disease</subject><subject>Pathogenesis</subject><subject>Pathology</subject><subject>Pathways</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Receptor Cross-Talk - physiology</subject><subject>Signal Transduction - genetics</subject><subject>Signal Transduction - physiology</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical analysis</subject><subject>Statistics</subject><subject>Studies</subject><subject>Systems Biology - methods</subject><subject>Systems Integration</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk0tv1DAUhSMEoqXwDxBEQqJiMYNfccYbpKriMVKlIl5by3GcjKcZO_V1CvPv8TBpmaAuUBZJfL9zbnzim2XPMZpjWuK3az8Ep7p5752ZI4S5wOWD7BgLSmacIPrw4PkoewKwRqigC84fZ0cEU85EQY6zq2VtXLTN1ro2196BcTBAXlswCkzeq7j6qbaQW5d_VuHKOvDu9G99gJ1OuVSPpg0q2huTwxai2UBeWd_5dpurvg9e6dXT7FGjOjDPxvtJ9v3D-2_nn2YXlx-X52cXM532EGecM6UVLonWJalpk941r7RuhBa4KXghFCma2hgtGqqJWrDKFKSsFgSxqq4NPcle7n37zoMccwKJKSa4XOASJWK5J2qv1rIPdqPCVnpl5Z8FH1qpQrS6M7IRvGIY11yUNSsqJnQKEWtGF0WjS7Tr9m7sNlQbU-sUZ1DdxHRacXYlW38jKWIUCZYMTkeD4K8HA1FuLGjTdcoZP4BcFAVBKKGJfPUPef_mRqpV6futa3xqq3ee8oyVXCBGCpKo-T1UumqzsekgmMam9YngzUSQmGh-xVYNAHL59cv_s5c_puzrA3ZlVBdX4Lsh2nQapyDbgzp4gGCau4wxkruRuE1D7kZCjiORZC8O_8-d6HYG6G82egi1</recordid><startdate>20110222</startdate><enddate>20110222</enddate><creator>Edwards, Yvonne J K</creator><creator>Beecham, Gary W</creator><creator>Scott, William K</creator><creator>Khuri, Sawsan</creator><creator>Bademci, Guney</creator><creator>Tekin, Demet</creator><creator>Martin, Eden R</creator><creator>Jiang, Zhijie</creator><creator>Mash, Deborah C</creator><creator>ffrench-Mullen, Jarlath</creator><creator>Pericak-Vance, Margaret A</creator><creator>Tsinoremas, Nicholas</creator><creator>Vance, Jeffery M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110222</creationdate><title>Identifying consensus disease pathways in Parkinson's disease using an integrative systems biology approach</title><author>Edwards, Yvonne J K ; Beecham, Gary W ; Scott, William K ; Khuri, Sawsan ; Bademci, Guney ; Tekin, Demet ; Martin, Eden R ; Jiang, Zhijie ; Mash, Deborah C ; ffrench-Mullen, Jarlath ; Pericak-Vance, Margaret A ; Tsinoremas, Nicholas ; Vance, Jeffery M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-664aca172cc72d3f664c6bccf9c91f5659a25fdeec9f3c2a84be527b8204bdde3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acids</topic><topic>Analysis</topic><topic>Axon guidance</topic><topic>Bioinformatics</topic><topic>Biological effects</topic><topic>Biology</topic><topic>Brain</topic><topic>Calcium</topic><topic>Calcium signalling</topic><topic>Chromosome Mapping - methods</topic><topic>Chromosome Mapping - statistics & numerical data</topic><topic>Consensus</topic><topic>Encyclopedias</topic><topic>Etiology</topic><topic>Gene expression</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Profiling - statistics & numerical data</topic><topic>Gene Regulatory Networks</topic><topic>Genes</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic research</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study - methods</topic><topic>Genome-Wide Association Study - statistics & numerical data</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Humans</topic><topic>Insects</topic><topic>Kinases</topic><topic>MAP Kinase Signaling System - genetics</topic><topic>MAP Kinase Signaling System - physiology</topic><topic>Mathematics</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Meta-analysis</topic><topic>Metabolic Networks and Pathways - genetics</topic><topic>Models, Biological</topic><topic>Movement disorders</topic><topic>Neurodegenerative diseases</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson's disease</topic><topic>Parkinsons disease</topic><topic>Pathogenesis</topic><topic>Pathology</topic><topic>Pathways</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Receptor Cross-Talk - physiology</topic><topic>Signal Transduction - genetics</topic><topic>Signal Transduction - physiology</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Statistical analysis</topic><topic>Statistics</topic><topic>Studies</topic><topic>Systems Biology - methods</topic><topic>Systems Integration</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Edwards, Yvonne J K</creatorcontrib><creatorcontrib>Beecham, Gary W</creatorcontrib><creatorcontrib>Scott, William K</creatorcontrib><creatorcontrib>Khuri, Sawsan</creatorcontrib><creatorcontrib>Bademci, Guney</creatorcontrib><creatorcontrib>Tekin, Demet</creatorcontrib><creatorcontrib>Martin, Eden R</creatorcontrib><creatorcontrib>Jiang, Zhijie</creatorcontrib><creatorcontrib>Mash, Deborah C</creatorcontrib><creatorcontrib>ffrench-Mullen, Jarlath</creatorcontrib><creatorcontrib>Pericak-Vance, Margaret A</creatorcontrib><creatorcontrib>Tsinoremas, Nicholas</creatorcontrib><creatorcontrib>Vance, Jeffery M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale in Context : Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Database (1962 - current)</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest advanced technologies & aerospace journals</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Edwards, Yvonne J K</au><au>Beecham, Gary W</au><au>Scott, William K</au><au>Khuri, Sawsan</au><au>Bademci, Guney</au><au>Tekin, Demet</au><au>Martin, Eden R</au><au>Jiang, Zhijie</au><au>Mash, Deborah C</au><au>ffrench-Mullen, Jarlath</au><au>Pericak-Vance, Margaret A</au><au>Tsinoremas, Nicholas</au><au>Vance, Jeffery M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identifying consensus disease pathways in Parkinson's disease using an integrative systems biology approach</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-02-22</date><risdate>2011</risdate><volume>6</volume><issue>2</issue><spage>e16917</spage><epage>e16917</epage><pages>e16917-e16917</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both GWAS and gene expression. The top 5000 SNPs (p<0.01) from a joint analysis of three existing PD GWAS were identified and each assigned to a gene. For gene expression, rather than the traditional comparison of one anatomical region between sets of patients and controls, we identified differentially expressed genes between adjacent Braak regions in each individual and adjusted using average control expression profiles. Over-represented pathways were calculated using a hyper-geometric statistical comparison. An integrated, systems meta-analysis of the over-represented pathways combined the expression and GWAS results using a Fisher's combined probability test. Four of the top seven pathways from each approach were identical. The top three pathways in the meta-analysis, with their corrected p-values, were axonal guidance (p = 2.8E-07), focal adhesion (p = 7.7E-06) and calcium signaling (p = 2.9E-05). These results support that a systems biology (pathway) approach will provide additional insight into the genetic etiology of PD and that these pathways have both biological and statistical support to be important in PD.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21364952</pmid><doi>10.1371/journal.pone.0016917</doi><tpages>e16917</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2011-02, Vol.6 (2), p.e16917-e16917 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1312178170 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; EZB Free E-Journals; DOAJ Directory of Open Access Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acids Analysis Axon guidance Bioinformatics Biological effects Biology Brain Calcium Calcium signalling Chromosome Mapping - methods Chromosome Mapping - statistics & numerical data Consensus Encyclopedias Etiology Gene expression Gene Expression Profiling - methods Gene Expression Profiling - statistics & numerical data Gene Regulatory Networks Genes Genetic Predisposition to Disease Genetic research Genome-wide association studies Genome-Wide Association Study - methods Genome-Wide Association Study - statistics & numerical data Genomes Genomics Humans Insects Kinases MAP Kinase Signaling System - genetics MAP Kinase Signaling System - physiology Mathematics Medical research Medicine Meta-analysis Metabolic Networks and Pathways - genetics Models, Biological Movement disorders Neurodegenerative diseases Parkinson Disease - genetics Parkinson's disease Parkinsons disease Pathogenesis Pathology Pathways Polymorphism, Single Nucleotide Receptor Cross-Talk - physiology Signal Transduction - genetics Signal Transduction - physiology Single nucleotide polymorphisms Single-nucleotide polymorphism Statistical analysis Statistics Studies Systems Biology - methods Systems Integration |
| title | Identifying consensus disease pathways in Parkinson's disease using an integrative systems biology approach |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T17%3A24%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Identifying%20consensus%20disease%20pathways%20in%20Parkinson's%20disease%20using%20an%20integrative%20systems%20biology%20approach&rft.jtitle=PloS%20one&rft.au=Edwards,%20Yvonne%20J%20K&rft.date=2011-02-22&rft.volume=6&rft.issue=2&rft.spage=e16917&rft.epage=e16917&rft.pages=e16917-e16917&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0016917&rft_dat=%3Cgale_plos_%3EA476904252%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1312178170&rft_id=info:pmid/21364952&rft_galeid=A476904252&rft_doaj_id=oai_doaj_org_article_f96b411d697d45b49c5381c4385fc70e&rfr_iscdi=true |