All that glitters is not gold - founder effects complicate associations of flu mutations to disease severity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-12

AUTHORS

Raphael TC Lee, Cecília LS Santos, Terezinha Maria de Paiva, Lin Cui, Fernanda L Sirota, Frank Eisenhaber, Sebastian Maurer-Stroh

ABSTRACT

BACKGROUND: The recent 2009 (H1N1) influenza A pandemic saw a rapid spread of the virus to essentially all parts of the world. In the course of its evolution, the virus acquired many mutations, some of which have been investigated in the context of increased severity due to high occurrences in fatal cases. For example, statements such as: "42.9% of individuals who died from laboratory-confirmed cases of the pandemic (H1N1) were infected with the hemagglutinin (HA) Q310 H mutant virus." give the impression that HA-Q310 H would be highly dangerous or important, while careful consideration of all available data suggests that this is unlikely to be the case. RESULTS: We compare the mutations HA-Q310 H, PB2-K340N, HA-D239N and HA-D239G using whole genome phylogenetic trees, structural modeling in their 3 D context and complete epidemiological data from sequences to clinical outcomes. HA-Q310 H and PB2-K340N appear as isolated subtrees in the phylogenetic analysis pointing to founder effects which is consistent with their clustered temporal appearance as well as the lack of an immediate structural basis that could explain a change of phenotypes. Considering the prevailing viral genomic background, shared origin of samples (all from the city of Sao Paulo) and narrow temporal window (all death case samples within 1 month), it becomes clear that HA-Q310 H was actually a generally common mutation in the region at that time which could readily explain its increased occurrence among the few analyzed fatal cases without requiring necessarily an association with severity. In further support of this, we highlight 3 mild cases with the HA-Q310 H mutation. CONCLUSIONS: We argue that claims of severity of any current and future flu mutation need to be critically considered in the light of phylogenetic, structural and detailed epidemiological data to distinguish increased occurrence due to possible founder effects rather than real phenotypic changes. More... »

PAGES

297

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1743-422x-7-297

DOI

http://dx.doi.org/10.1186/1743-422x-7-297

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1014469508

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21040570


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Genetics", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Founder Effect", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Hemagglutinins, Viral", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Influenza A Virus, H1N1 Subtype", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Influenza, Human", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Models, Molecular", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mutation, Missense", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Phylogeny", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Prevalence", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Protein Structure, Tertiary", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "RNA, Viral", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Virulence", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Virulence Factors", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Agency for Science, Technology and Research", 
          "id": "https://www.grid.ac/institutes/grid.185448.4", 
          "name": [
            "Agency for Science Technology and Research (A*STAR), #07-01, Matrix, Bioinformatics Institute (BII), College Station, 30 Biopolis Street, 138671, Singapore"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lee", 
        "givenName": "Raphael TC", 
        "id": "sg:person.012003577422.41", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012003577422.41"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Centro de Virologia, Instituto Adolfo Lutz (IAL). Av. Dr Arnaldo, 30 Biopolis Street, 01246/902, S\u00e3o Paulo, SP, Brasil"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Santos", 
        "givenName": "Cec\u00edlia LS", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "name": [
            "Centro de Virologia, Instituto Adolfo Lutz (IAL). Av. Dr Arnaldo, 30 Biopolis Street, 01246/902, S\u00e3o Paulo, SP, Brasil"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Maria de Paiva", 
        "givenName": "Terezinha", 
        "id": "sg:person.01132554665.82", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01132554665.82"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Ministry of Health", 
          "id": "https://www.grid.ac/institutes/grid.415698.7", 
          "name": [
            "Ministry of Health (MOH), National Public Health Laboratory (NPHL), Singapore"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cui", 
        "givenName": "Lin", 
        "id": "sg:person.0723754433.61", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0723754433.61"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Agency for Science, Technology and Research", 
          "id": "https://www.grid.ac/institutes/grid.185448.4", 
          "name": [
            "Agency for Science Technology and Research (A*STAR), #07-01, Matrix, Bioinformatics Institute (BII), College Station, 30 Biopolis Street, 138671, Singapore"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sirota", 
        "givenName": "Fernanda L", 
        "id": "sg:person.01263776345.48", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01263776345.48"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Nanyang Technological University", 
          "id": "https://www.grid.ac/institutes/grid.59025.3b", 
          "name": [
            "Agency for Science Technology and Research (A*STAR), #07-01, Matrix, Bioinformatics Institute (BII), College Station, 30 Biopolis Street, 138671, Singapore", 
            "Department of Biological Sciences (DBS), 8 Medical Drive, National University of Singapore (NUS), 117597, Singapore", 
            "School of Computer Engineering (SCE), Nanyang Technological University (NTU), 50 Nanyang Drive, 637553, Singapore"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Eisenhaber", 
        "givenName": "Frank", 
        "id": "sg:person.01343070544.19", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01343070544.19"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Nanyang Technological University", 
          "id": "https://www.grid.ac/institutes/grid.59025.3b", 
          "name": [
            "Agency for Science Technology and Research (A*STAR), #07-01, Matrix, Bioinformatics Institute (BII), College Station, 30 Biopolis Street, 138671, Singapore", 
            "School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, 637551, Singapore"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Maurer-Stroh", 
        "givenName": "Sebastian", 
        "id": "sg:person.0625334350.76", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0625334350.76"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1093/molbev/msm092", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001758106"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/nar/gkq089", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004556131"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1471-2148-7-214", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010584451", 
          "https://doi.org/10.1186/1471-2148-7-214"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/nar/gki198", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013017359"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1186430", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014374607"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1186430", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014374607"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/bioinformatics/btl158", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014668137"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/currents.rrn1149", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015142062"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1131528", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021499226"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/currents.rrn1162", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021851847"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.meegid.2007.08.001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021987044"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/1745-6150-4-18", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023545753", 
          "https://doi.org/10.1186/1745-6150-4-18"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nsmb.1421", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026955344", 
          "https://doi.org/10.1038/nsmb.1421"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08182", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030155839", 
          "https://doi.org/10.1038/nature08182"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature08182", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030155839", 
          "https://doi.org/10.1038/nature08182"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jvi.75.23.11686-11699.2001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1032928630"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1176225", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033162360"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1126/science.1176225", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033162360"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0009068", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035812118"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/prot.10104", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1041865756"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/jvi.02005-07", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042086158"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/currents.rrn1126", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043343318"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0009549", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1051378431"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1080/10635150390235520", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1058369386"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/cc.9.5.10913", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1072301386"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1078039259", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2807/ese.15.09.19498-en", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1078059188"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1078146160", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1078153312", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1079090079", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2010-12", 
    "datePublishedReg": "2010-12-01", 
    "description": "BACKGROUND: The recent 2009 (H1N1) influenza A pandemic saw a rapid spread of the virus to essentially all parts of the world. In the course of its evolution, the virus acquired many mutations, some of which have been investigated in the context of increased severity due to high occurrences in fatal cases. For example, statements such as: \"42.9% of individuals who died from laboratory-confirmed cases of the pandemic (H1N1) were infected with the hemagglutinin (HA) Q310 H mutant virus.\" give the impression that HA-Q310 H would be highly dangerous or important, while careful consideration of all available data suggests that this is unlikely to be the case.\nRESULTS: We compare the mutations HA-Q310 H, PB2-K340N, HA-D239N and HA-D239G using whole genome phylogenetic trees, structural modeling in their 3 D context and complete epidemiological data from sequences to clinical outcomes. HA-Q310 H and PB2-K340N appear as isolated subtrees in the phylogenetic analysis pointing to founder effects which is consistent with their clustered temporal appearance as well as the lack of an immediate structural basis that could explain a change of phenotypes. Considering the prevailing viral genomic background, shared origin of samples (all from the city of Sao Paulo) and narrow temporal window (all death case samples within 1 month), it becomes clear that HA-Q310 H was actually a generally common mutation in the region at that time which could readily explain its increased occurrence among the few analyzed fatal cases without requiring necessarily an association with severity. In further support of this, we highlight 3 mild cases with the HA-Q310 H mutation.\nCONCLUSIONS: We argue that claims of severity of any current and future flu mutation need to be critically considered in the light of phylogenetic, structural and detailed epidemiological data to distinguish increased occurrence due to possible founder effects rather than real phenotypic changes.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1186/1743-422x-7-297", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1034449", 
        "issn": [
          "1743-422X"
        ], 
        "name": "Virology Journal", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "7"
      }
    ], 
    "name": "All that glitters is not gold - founder effects complicate associations of flu mutations to disease severity", 
    "pagination": "297", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "44ef0d97b2f5b08292da352014e6c520e926fd25ca126c92476e09c0a48cfb75"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "21040570"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101231645"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/1743-422x-7-297"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1014469508"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/1743-422x-7-297", 
      "https://app.dimensions.ai/details/publication/pub.1014469508"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T13:16", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8659_00000511.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://link.springer.com/10.1186%2F1743-422X-7-297"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/1743-422x-7-297'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/1743-422x-7-297'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/1743-422x-7-297'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/1743-422x-7-297'


 

This table displays all metadata directly associated to this object as RDF triples.

255 TRIPLES      21 PREDICATES      69 URIs      34 LITERALS      22 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/1743-422x-7-297 schema:about N4605a481916b49fab9ed2e35d49b17ac
2 N71740287294e456ea39c1a923139d569
3 N723da00f52ee4f4c84f3283bb330ffa3
4 N752734b4b0404934a01f1020dd5f1ce6
5 N8923b3c2095a462caf1042b6a92a92d0
6 N9aa90a0967834acbb5423fa7f6b04181
7 Nbd30963f65fc4fcaa829637f74635fef
8 Nc8c85d3b85634a91a5b17dcb97aac8ff
9 Nda4a1ee780b140348e271d496faa6b32
10 Ne5fa617b08bc418bb56a84d5279a2b7e
11 Nf03f28c29c6b429aa1e84ac9e006ca88
12 Nf0555aa1655c49d1ac30cf3a7aa22178
13 Nf8dc5a7a098843dca9ceb604543d0f97
14 anzsrc-for:06
15 anzsrc-for:0604
16 schema:author Nc399c84bfb644fc49fa9ad32730a5e76
17 schema:citation sg:pub.10.1038/nature08182
18 sg:pub.10.1038/nsmb.1421
19 sg:pub.10.1186/1471-2148-7-214
20 sg:pub.10.1186/1745-6150-4-18
21 https://app.dimensions.ai/details/publication/pub.1078039259
22 https://app.dimensions.ai/details/publication/pub.1078146160
23 https://app.dimensions.ai/details/publication/pub.1078153312
24 https://app.dimensions.ai/details/publication/pub.1079090079
25 https://doi.org/10.1002/prot.10104
26 https://doi.org/10.1016/j.meegid.2007.08.001
27 https://doi.org/10.1080/10635150390235520
28 https://doi.org/10.1093/bioinformatics/btl158
29 https://doi.org/10.1093/molbev/msm092
30 https://doi.org/10.1093/nar/gki198
31 https://doi.org/10.1093/nar/gkq089
32 https://doi.org/10.1126/science.1131528
33 https://doi.org/10.1126/science.1176225
34 https://doi.org/10.1126/science.1186430
35 https://doi.org/10.1128/jvi.02005-07
36 https://doi.org/10.1128/jvi.75.23.11686-11699.2001
37 https://doi.org/10.1371/currents.rrn1126
38 https://doi.org/10.1371/currents.rrn1149
39 https://doi.org/10.1371/currents.rrn1162
40 https://doi.org/10.1371/journal.pone.0009068
41 https://doi.org/10.1371/journal.pone.0009549
42 https://doi.org/10.2807/ese.15.09.19498-en
43 https://doi.org/10.4161/cc.9.5.10913
44 schema:datePublished 2010-12
45 schema:datePublishedReg 2010-12-01
46 schema:description BACKGROUND: The recent 2009 (H1N1) influenza A pandemic saw a rapid spread of the virus to essentially all parts of the world. In the course of its evolution, the virus acquired many mutations, some of which have been investigated in the context of increased severity due to high occurrences in fatal cases. For example, statements such as: "42.9% of individuals who died from laboratory-confirmed cases of the pandemic (H1N1) were infected with the hemagglutinin (HA) Q310 H mutant virus." give the impression that HA-Q310 H would be highly dangerous or important, while careful consideration of all available data suggests that this is unlikely to be the case. RESULTS: We compare the mutations HA-Q310 H, PB2-K340N, HA-D239N and HA-D239G using whole genome phylogenetic trees, structural modeling in their 3 D context and complete epidemiological data from sequences to clinical outcomes. HA-Q310 H and PB2-K340N appear as isolated subtrees in the phylogenetic analysis pointing to founder effects which is consistent with their clustered temporal appearance as well as the lack of an immediate structural basis that could explain a change of phenotypes. Considering the prevailing viral genomic background, shared origin of samples (all from the city of Sao Paulo) and narrow temporal window (all death case samples within 1 month), it becomes clear that HA-Q310 H was actually a generally common mutation in the region at that time which could readily explain its increased occurrence among the few analyzed fatal cases without requiring necessarily an association with severity. In further support of this, we highlight 3 mild cases with the HA-Q310 H mutation. CONCLUSIONS: We argue that claims of severity of any current and future flu mutation need to be critically considered in the light of phylogenetic, structural and detailed epidemiological data to distinguish increased occurrence due to possible founder effects rather than real phenotypic changes.
47 schema:genre research_article
48 schema:inLanguage en
49 schema:isAccessibleForFree true
50 schema:isPartOf N08e750d6b3884a75b5036adb14c55222
51 Neef725825c8547e2856b2ee442f02e59
52 sg:journal.1034449
53 schema:name All that glitters is not gold - founder effects complicate associations of flu mutations to disease severity
54 schema:pagination 297
55 schema:productId N1f362e21e990459b873f5efc5e958b8b
56 N43081ec443834b2484b7f761b6870c72
57 N725462cec3ce46d3a0fc751068063afc
58 N9b8b3b8324344e94a95050f3adda7b56
59 Ne9acd9d902ae4a139662d949c6e5c438
60 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014469508
61 https://doi.org/10.1186/1743-422x-7-297
62 schema:sdDatePublished 2019-04-10T13:16
63 schema:sdLicense https://scigraph.springernature.com/explorer/license/
64 schema:sdPublisher Nda013dad3b5d4d8c90964fe570b20633
65 schema:url http://link.springer.com/10.1186%2F1743-422X-7-297
66 sgo:license sg:explorer/license/
67 sgo:sdDataset articles
68 rdf:type schema:ScholarlyArticle
69 N05d948b135db49e2a1bc16614fd5cd75 rdf:first sg:person.01263776345.48
70 rdf:rest Nee7852d4a3ed42bd93c21245372f69a0
71 N08e750d6b3884a75b5036adb14c55222 schema:volumeNumber 7
72 rdf:type schema:PublicationVolume
73 N0d1319983462496fbc40ce76e374e16a schema:name Centro de Virologia, Instituto Adolfo Lutz (IAL). Av. Dr Arnaldo, 30 Biopolis Street, 01246/902, São Paulo, SP, Brasil
74 rdf:type schema:Organization
75 N1f362e21e990459b873f5efc5e958b8b schema:name readcube_id
76 schema:value 44ef0d97b2f5b08292da352014e6c520e926fd25ca126c92476e09c0a48cfb75
77 rdf:type schema:PropertyValue
78 N43081ec443834b2484b7f761b6870c72 schema:name pubmed_id
79 schema:value 21040570
80 rdf:type schema:PropertyValue
81 N4605a481916b49fab9ed2e35d49b17ac schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
82 schema:name Phylogeny
83 rdf:type schema:DefinedTerm
84 N67adc1c28c6a433494cfe166c1dfa799 schema:affiliation Nb0cd14ed078b4f82b92357d9424afe9e
85 schema:familyName Santos
86 schema:givenName Cecília LS
87 rdf:type schema:Person
88 N71740287294e456ea39c1a923139d569 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
89 schema:name Humans
90 rdf:type schema:DefinedTerm
91 N723da00f52ee4f4c84f3283bb330ffa3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
92 schema:name Influenza, Human
93 rdf:type schema:DefinedTerm
94 N725462cec3ce46d3a0fc751068063afc schema:name dimensions_id
95 schema:value pub.1014469508
96 rdf:type schema:PropertyValue
97 N752734b4b0404934a01f1020dd5f1ce6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
98 schema:name Models, Molecular
99 rdf:type schema:DefinedTerm
100 N821b821385fe4875a6307a1beb3f7021 rdf:first sg:person.0723754433.61
101 rdf:rest N05d948b135db49e2a1bc16614fd5cd75
102 N8923b3c2095a462caf1042b6a92a92d0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
103 schema:name Influenza A Virus, H1N1 Subtype
104 rdf:type schema:DefinedTerm
105 N9aa90a0967834acbb5423fa7f6b04181 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
106 schema:name Mutation, Missense
107 rdf:type schema:DefinedTerm
108 N9b8b3b8324344e94a95050f3adda7b56 schema:name nlm_unique_id
109 schema:value 101231645
110 rdf:type schema:PropertyValue
111 Nafae8c2658284241bdc418846a46e4b5 rdf:first sg:person.0625334350.76
112 rdf:rest rdf:nil
113 Nb0cd14ed078b4f82b92357d9424afe9e schema:name Centro de Virologia, Instituto Adolfo Lutz (IAL). Av. Dr Arnaldo, 30 Biopolis Street, 01246/902, São Paulo, SP, Brasil
114 rdf:type schema:Organization
115 Nbd30963f65fc4fcaa829637f74635fef schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
116 schema:name Hemagglutinins, Viral
117 rdf:type schema:DefinedTerm
118 Nc399c84bfb644fc49fa9ad32730a5e76 rdf:first sg:person.012003577422.41
119 rdf:rest Nd66085c134dd4524a4e9933b469fdb8e
120 Nc8c85d3b85634a91a5b17dcb97aac8ff schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
121 schema:name Virulence
122 rdf:type schema:DefinedTerm
123 Nd66085c134dd4524a4e9933b469fdb8e rdf:first N67adc1c28c6a433494cfe166c1dfa799
124 rdf:rest Nf1bbae3c87944d68a5364ccc4c8e4d36
125 Nda013dad3b5d4d8c90964fe570b20633 schema:name Springer Nature - SN SciGraph project
126 rdf:type schema:Organization
127 Nda4a1ee780b140348e271d496faa6b32 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
128 schema:name Prevalence
129 rdf:type schema:DefinedTerm
130 Ne5fa617b08bc418bb56a84d5279a2b7e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
131 schema:name RNA, Viral
132 rdf:type schema:DefinedTerm
133 Ne9acd9d902ae4a139662d949c6e5c438 schema:name doi
134 schema:value 10.1186/1743-422x-7-297
135 rdf:type schema:PropertyValue
136 Nee7852d4a3ed42bd93c21245372f69a0 rdf:first sg:person.01343070544.19
137 rdf:rest Nafae8c2658284241bdc418846a46e4b5
138 Neef725825c8547e2856b2ee442f02e59 schema:issueNumber 1
139 rdf:type schema:PublicationIssue
140 Nf03f28c29c6b429aa1e84ac9e006ca88 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
141 schema:name Virulence Factors
142 rdf:type schema:DefinedTerm
143 Nf0555aa1655c49d1ac30cf3a7aa22178 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
144 schema:name Founder Effect
145 rdf:type schema:DefinedTerm
146 Nf1bbae3c87944d68a5364ccc4c8e4d36 rdf:first sg:person.01132554665.82
147 rdf:rest N821b821385fe4875a6307a1beb3f7021
148 Nf8dc5a7a098843dca9ceb604543d0f97 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
149 schema:name Protein Structure, Tertiary
150 rdf:type schema:DefinedTerm
151 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
152 schema:name Biological Sciences
153 rdf:type schema:DefinedTerm
154 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
155 schema:name Genetics
156 rdf:type schema:DefinedTerm
157 sg:journal.1034449 schema:issn 1743-422X
158 schema:name Virology Journal
159 rdf:type schema:Periodical
160 sg:person.01132554665.82 schema:affiliation N0d1319983462496fbc40ce76e374e16a
161 schema:familyName Maria de Paiva
162 schema:givenName Terezinha
163 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01132554665.82
164 rdf:type schema:Person
165 sg:person.012003577422.41 schema:affiliation https://www.grid.ac/institutes/grid.185448.4
166 schema:familyName Lee
167 schema:givenName Raphael TC
168 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012003577422.41
169 rdf:type schema:Person
170 sg:person.01263776345.48 schema:affiliation https://www.grid.ac/institutes/grid.185448.4
171 schema:familyName Sirota
172 schema:givenName Fernanda L
173 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01263776345.48
174 rdf:type schema:Person
175 sg:person.01343070544.19 schema:affiliation https://www.grid.ac/institutes/grid.59025.3b
176 schema:familyName Eisenhaber
177 schema:givenName Frank
178 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01343070544.19
179 rdf:type schema:Person
180 sg:person.0625334350.76 schema:affiliation https://www.grid.ac/institutes/grid.59025.3b
181 schema:familyName Maurer-Stroh
182 schema:givenName Sebastian
183 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0625334350.76
184 rdf:type schema:Person
185 sg:person.0723754433.61 schema:affiliation https://www.grid.ac/institutes/grid.415698.7
186 schema:familyName Cui
187 schema:givenName Lin
188 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0723754433.61
189 rdf:type schema:Person
190 sg:pub.10.1038/nature08182 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030155839
191 https://doi.org/10.1038/nature08182
192 rdf:type schema:CreativeWork
193 sg:pub.10.1038/nsmb.1421 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026955344
194 https://doi.org/10.1038/nsmb.1421
195 rdf:type schema:CreativeWork
196 sg:pub.10.1186/1471-2148-7-214 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010584451
197 https://doi.org/10.1186/1471-2148-7-214
198 rdf:type schema:CreativeWork
199 sg:pub.10.1186/1745-6150-4-18 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023545753
200 https://doi.org/10.1186/1745-6150-4-18
201 rdf:type schema:CreativeWork
202 https://app.dimensions.ai/details/publication/pub.1078039259 schema:CreativeWork
203 https://app.dimensions.ai/details/publication/pub.1078146160 schema:CreativeWork
204 https://app.dimensions.ai/details/publication/pub.1078153312 schema:CreativeWork
205 https://app.dimensions.ai/details/publication/pub.1079090079 schema:CreativeWork
206 https://doi.org/10.1002/prot.10104 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041865756
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1016/j.meegid.2007.08.001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021987044
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1080/10635150390235520 schema:sameAs https://app.dimensions.ai/details/publication/pub.1058369386
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1093/bioinformatics/btl158 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014668137
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1093/molbev/msm092 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001758106
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1093/nar/gki198 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013017359
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1093/nar/gkq089 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004556131
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1126/science.1131528 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021499226
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1126/science.1176225 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033162360
223 rdf:type schema:CreativeWork
224 https://doi.org/10.1126/science.1186430 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014374607
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1128/jvi.02005-07 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042086158
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1128/jvi.75.23.11686-11699.2001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032928630
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1371/currents.rrn1126 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043343318
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1371/currents.rrn1149 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015142062
233 rdf:type schema:CreativeWork
234 https://doi.org/10.1371/currents.rrn1162 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021851847
235 rdf:type schema:CreativeWork
236 https://doi.org/10.1371/journal.pone.0009068 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035812118
237 rdf:type schema:CreativeWork
238 https://doi.org/10.1371/journal.pone.0009549 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051378431
239 rdf:type schema:CreativeWork
240 https://doi.org/10.2807/ese.15.09.19498-en schema:sameAs https://app.dimensions.ai/details/publication/pub.1078059188
241 rdf:type schema:CreativeWork
242 https://doi.org/10.4161/cc.9.5.10913 schema:sameAs https://app.dimensions.ai/details/publication/pub.1072301386
243 rdf:type schema:CreativeWork
244 https://www.grid.ac/institutes/grid.185448.4 schema:alternateName Agency for Science, Technology and Research
245 schema:name Agency for Science Technology and Research (A*STAR), #07-01, Matrix, Bioinformatics Institute (BII), College Station, 30 Biopolis Street, 138671, Singapore
246 rdf:type schema:Organization
247 https://www.grid.ac/institutes/grid.415698.7 schema:alternateName Ministry of Health
248 schema:name Ministry of Health (MOH), National Public Health Laboratory (NPHL), Singapore
249 rdf:type schema:Organization
250 https://www.grid.ac/institutes/grid.59025.3b schema:alternateName Nanyang Technological University
251 schema:name Agency for Science Technology and Research (A*STAR), #07-01, Matrix, Bioinformatics Institute (BII), College Station, 30 Biopolis Street, 138671, Singapore
252 Department of Biological Sciences (DBS), 8 Medical Drive, National University of Singapore (NUS), 117597, Singapore
253 School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, 637551, Singapore
254 School of Computer Engineering (SCE), Nanyang Technological University (NTU), 50 Nanyang Drive, 637553, Singapore
255 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...