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A formalization of one of the main claims of “FTO Obesity Variant Circuitry and Adipocyte Browning in Humans” by Claussnitzer et al. 20151

Issue title: Semantic Publishing with Formalization Papers

Guest editors: Cristina-Iulia Bucur and Tobias Kuhn

Article type: Formalization Paper

Authors: Joslin, Amelia; *

Affiliations: Maze Therapeutics, USA

Correspondence: [*] Corresponding author. E-mail: ajoslin@mazetx.com.

Note: [1] As RDF/nanopublication: http://purl.org/np/RAxBBJ2WkonyQNlXfdCAOaCi64J_xqgVGeaLjVQow9M88

Keywords: Early human adipogenesis, regulatory element within the first intron of FTO, expression of genes IRX3 and IRX5

DOI: 10.3233/DS-210038

Journal: Data Science, vol. 5, no. 1, pp. 11-15, 2022

Received 21 June 2021
|
Accepted 12 November 2021
|
Published: 22 March 2022
Get PDF open access

Abstract

Claussnitzer et al. claimed in previous work that a regulatory element within the first intron of FTO affects IRX3 and IRX5 expression during early adipogenesis. We present here a formalization of that claim, stating that all things of class “early human adipogenesis” that are in the context of a thing of class “regulatory element within the first intron of FTO” generally have a relation of type “affects” to a thing of class “expression of genes IRX3 and IRX5” in the same context.

1.Introduction

Claussnitzer et al. [1] state that “The rs1421085 T-to-C single-nucleotide variant disrupts a conserved motif for the ARID5B repressor, which leads to derepression of a potent preadipocyte enhancer and a doubling of IRX3 and IRX5 expression during early adipocyte differentiation.”. We present here a formalization of the main scientific claim from this quote by using a semantic template called the super-pattern [2].

2.Formalization

Our formalization looks as follows:

CONTEXT-CLASS (“in the context of all ...”):early human adipogenesis
SUBJECT-CLASS (“things of type ...”):regulatory element within the first intron of FTO
QUALIFIER:generally
RELATION-TYPE (“have a relation of type...”):affects
OBJECT-CLASS (“to things of type...”):expression of genes IRX3 and IRX5

In the context class we use a new minted class “early human adipogenesis” that is a subclass of “adipogenesis” (Q2824461) from Wikidata. In the subject class, we use a new minted class “regulatory element within the first intron of FTO” that is related to the class “FTO” (Q14912501) and “intron” (Q207551) from Wikidata. In the object class we minted a new class “expression of genes IRX3 and IRX5” that is a subclass of “gene expression” (Q26972) from Wikidata and is related to the class “IRX5” (Q18035174) and “IRX3” (Q18046058) from Wikidata.

3.RDF Code

This is our formalization as a nanopublication in TriG format:

@prefix this: <http://purl.org/np/RAxBBJ2WkonyQNlXfdCAOaCi64J_xqgVGeaLjVQow9M88> .
@prefix sub: <http://purl.org/np/RAxBBJ2WkonyQNlXfdCAOaCi64J_xqgVGeaLjVQow9M88#> .
@prefix np: <http://www.nanopub.org/nschema#> .
@prefix dct: <http://purl.org/dc/terms/> .
@prefix nt: <https://w3id.org/np/o/ntemplate/> .
@prefix npx: <http://purl.org/nanopub/x/> .
@prefix xsd: <http://www.w3.org/2001/XMLSchema#> .
@prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> .
@prefix orcid: <https://orcid.org/> .
@prefix prov: <http://www.w3.org/ns/prov#> .
@prefix sp: <https://w3id.org/linkflows/superpattern/terms/> .

sub:Head {
  this: np:hasAssertion sub:assertion ;
    np:hasProvenance sub:provenance ;
    np:hasPublicationInfo sub:pubinfo ;
    a np:Nanopublication .
}
sub:assertion {
  sub:spi a sp:SuperPatternInstance ;
    rdfs:label "A regulatory element within the first intron of FTO affects IRX3 and IRX5 expression during early
adipogenesis" ;
    sp:hasContextClass <http://purl.org/np/RAtsHwzNs36rGrLnoSbGrPD351Qw033Acoe4zmdXhsYlM#early-human-adipogenesis> ;
    sp:hasSubjectClass <http://purl.org/np/RAxLYvJ1JrRf2JAowYGbGJleQPmqtpXnXsIvse7GmLeT8#regulatory-element-within-the-first
-intron-of-FTO> ;
    sp:hasQualifier sp:generallyQualifier ;
    sp:hasRelation sp:affects ;
    sp:hasObjectClass <http://purl.org/np/RAwkXiTv7qCtqOYzlR6ozZRGLRtG6mlogrYdRQ1E4dRDg#expression-of-genes-IRX3-and-IRX5> .
}
sub:provenance {
  sub:activity a sp:FormalizationActivity ;
    prov:used sub:quote , <https://doi.org/10.1056/NEJMoa1502214> ;
    prov:wasAssociatedWith orcid:0000-0003-2432-4125 .
  sub:assertion prov:wasGeneratedBy sub:activity .
  sub:quote prov:value "The rs1421085 T-to-C single-nucleotide variant disrupts a conserved motif for the ARID5B repressor,
which leads to derepression of a potent preadipocyte enhancer and a doubling of IRX3 and IRX5 expression during
early adipocyte differentiation." ;
    prov:wasQuotedFrom <https://doi.org/10.1056/NEJMoa1502214> .
}
sub:pubinfo {
  sub:sig npx:hasAlgorithm "RSA" ;
    npx:hasPublicKey "MIGfMA0GCSqGSIb3DQEBAQUAA4GNADCBiQKBgQCS1s1OiABv1mrDnFWp9ecwHdQ+UlJn6JCDYXspRsbZgsm2QAiofbnVvf6gfkcjj
Scd5fq3sW/W8r/o7bdafVSd6xuTG/vHrO9Ax/guPiJ6O/Z57Hk0nQy6c+l71HpaJ2BPPWKOgYiFZ/8eulmuM6BJ8TDKxoBtcqP5QbvN9KYjlQIDAQAB" ;
    npx:hasSignature "MUs9dML4QrzQVnfT2hqnfkif+lpusIVT0o4c74M69kgNQmA0CXVRzUZIHcvavS/pMlobVFBhfkTQ7kHs5a0CZGVrvtOhQJYD17eXzg
6dwD/LqdYNYErvWxduyvwInXMasXpDZdYkFtddAFt/5Vny6BSBoiIzclnGfGwahZhFmpg=" ;
    npx:hasSignatureTarget this: .
  this: dct:created "2021-10-27T10:22:03.671-07:00"^^xsd:dateTime ;
    dct:creator orcid:0000-0003-2432-4125 ;
    npx:introduces sub:spi ;
    <https://w3id.org/linkflows/reviews/isUpdateOf> <http://purl.org/np/RAxxJWyH8OdTJLs-ZY1q5jVq1OWFNOoLFvwEcUFyR8EEo> ;
    nt:wasCreatedFromProvenanceTemplate <http://purl.org/np/RAB_oy10D3XUP-zYlqGz7Uj58AsUXhEKeGqmRFg5LSgDM> ;
    nt:wasCreatedFromPubinfoTemplate <http://purl.org/np/RAA2MfqdBCzmz9yVWjKLXNbyfBNcwsMmOqcNUxkk1maIM> ,
<http://purl.org/np/RAOGu9Lh0BD4tbIRB9RG6RGRA_ObDh75NTbIqaWgxxs8M> ;
    nt:wasCreatedFromTemplate <http://purl.org/np/RAv68imZrEjfcp2rnEg1hzoBqEVc0cQMtp9_1Za0BxNM4> .
}

The following nanopublications introduce the newly minted classes in TriG format.

This is the class definition of “early human adipogenesis”:

@prefix this: <http://purl.org/np/RAtsHwzNs36rGrLnoSbGrPD351Qw033Acoe4zmdXhsYlM> .
@prefix sub: <http://purl.org/np/RAtsHwzNs36rGrLnoSbGrPD351Qw033Acoe4zmdXhsYlM#> .
@prefix np: <http://www.nanopub.org/nschema#> .
@prefix dct: <http://purl.org/dc/terms/> .
@prefix nt: <https://w3id.org/np/o/ntemplate/> .
@prefix npx: <http://purl.org/nanopub/x/> .
@prefix xsd: <http://www.w3.org/2001/XMLSchema#> .
@prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> .
@prefix orcid: <https://orcid.org/> .
@prefix prov: <http://www.w3.org/ns/prov#> .
@prefix skos: <http://www.w3.org/2004/02/skos/core#> .

sub:Head {
  this: np:hasAssertion sub:assertion ;
    np:hasProvenance sub:provenance ;
    np:hasPublicationInfo sub:pubinfo ;
    a np:Nanopublication .
}
sub:assertion {
  sub:early-human-adipogenesis a <http://www.w3.org/2002/07/owl#Class> ;
    rdfs:label "early human adipogenesis" ;
    rdfs:subClassOf <http://www.wikidata.org/entity/Q2824461> ;
    skos:definition "early human adipogenesis" .
}
sub:provenance {
  sub:assertion prov:wasAttributedTo orcid:0000-0003-2432-4125 .
}
sub:pubinfo {
  sub:sig npx:hasAlgorithm "RSA" ;
    npx:hasPublicKey
"MIGfMA0GCSqGSIb3DQEBAQUAA4GNADCBiQKBgQCS1s1OiABv1mrDnFWp9ecwHdQ+UlJn6JCDYXspRsbZgsm2QAiofbnVvf6gfkcjjScd5fq3sW/W8r/
o7bdafVSd6xuTG/vHrO9Ax/guPiJ6O/Z57Hk0nQy6c+l71HpaJ2BPPWKOgYiFZ/8eulmuM6BJ8TDKxoBtcqP5QbvN9KYjlQIDAQAB" ;
    npx:hasSignature
"eiaG+BcxT16aKpKUpVosKrOxB6PON3szX55WGjEnlAwV87u5mA4huRHXOoDdC/4XgPvT40woR34zhB+VQvLJoizmk6rTPEVReNSG8vdxq3Wdbj6W4qJszBlmxb
+XFw2Awdj/4IzNIzK1/at9WQvIE5rV8tkYIvSnmLfWTxKvL/A=" ;
    npx:hasSignatureTarget this: .
  this: dct:created "2021-06-21T16:44:19.998-07:00"^^xsd:dateTime ;
    dct:creator orcid:0000-0003-2432-4125 ;
    npx:introduces sub:early-human-adipogenesis ;
    nt:wasCreatedFromProvenanceTemplate <http://purl.org/np/RANwQa4ICWS5SOjw7gp99nBpXBasapwtZF1fIM3H2gYTM> ;
    nt:wasCreatedFromPubinfoTemplate <http://purl.org/np/RAA2MfqdBCzmz9yVWjKLXNbyfBNcwsMmOqcNUxkk1maIM> ;
    nt:wasCreatedFromTemplate <http://purl.org/np/RAdpgRpigXtt8iPV9uOPf3wIT3qzOI8Sg2Q72CNV8g-Yo> .
}

This is the class definition of “regulatory element within the first intron of FTO”:

@prefix this: <http://purl.org/np/RAxLYvJ1JrRf2JAowYGbGJleQPmqtpXnXsIvse7GmLeT8> .
@prefix sub: <http://purl.org/np/RAxLYvJ1JrRf2JAowYGbGJleQPmqtpXnXsIvse7GmLeT8#> .
@prefix np: <http://www.nanopub.org/nschema#> .
@prefix dct: <http://purl.org/dc/terms/> .
@prefix nt: <https://w3id.org/np/o/ntemplate/> .
@prefix npx: <http://purl.org/nanopub/x/> .
@prefix xsd: <http://www.w3.org/2001/XMLSchema#> .
@prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> .
@prefix orcid: <https://orcid.org/> .
@prefix prov: <http://www.w3.org/ns/prov#> .
@prefix skos: <http://www.w3.org/2004/02/skos/core#> .

sub:Head {
  this: np:hasAssertion sub:assertion ;
    np:hasProvenance sub:provenance ;
    np:hasPublicationInfo sub:pubinfo ;
    a np:Nanopublication .
}
sub:assertion {
  sub:regulatory-element-within-the-first-intron-of-FTO a <http://www.w3.org/2002/07/owl#Class> ;
    rdfs:label "regulatory element within the first intron of FTO" ;
    skos:definition "a regulatory element present within the first intron of the human gene FTO" ;
    skos:relatedMatch <http://www.wikidata.org/entity/Q14912501> , <http://www.wikidata.org/entity/Q207551> .
}
sub:provenance {
  sub:assertion prov:wasAttributedTo orcid:0000-0003-2432-4125 .
}
sub:pubinfo {
  sub:sig npx:hasAlgorithm "RSA" ;
    npx:hasPublicKey
"MIGfMA0GCSqGSIb3DQEBAQUAA4GNADCBiQKBgQCS1s1OiABv1mrDnFWp9ecwHdQ+UlJn6JCDYXspRsbZgsm2QAiofbnVvf6gfkcjjScd5fq3sW/W8r/
o7bdafVSd6xuTG/vHrO9Ax/guPiJ6O/Z57Hk0nQy6c+l71HpaJ2BPPWKOgYiFZ/8eulmuM6BJ8TDKxoBtcqP5QbvN9KYjlQIDAQAB" ;
    npx:hasSignature
"M8cVwUkflLAuLqLUM+ul7EdLSXQhcSsbERJUcBwTF2Ri78XD6JNdHsF5+Qekg3xefqy7d8530m2RHPxjSkooNi3XAOZWsd2T6OZiZ0lSmAIsaRarmsnHbl/
GDf0OS4OiqCL1jVFNXMosdVd9runltov655znbpiFBJxmMd66+v0=" ;
    npx:hasSignatureTarget this: .
  this: dct:created "2021-10-27T10:04:01.217-07:00"^^xsd:dateTime ;
    dct:creator orcid:0000-0003-2432-4125 ;
    npx:introduces sub:regulatory-element-within-the-first-intron-of-FTO ;
    npx:supersedes <http://purl.org/np/RANAxL2OxGmP9VAN6cUi_0KEK0rJb9bPn4l1A5HquXKrI> ;
    <https://w3id.org/linkflows/reviews/isUpdateOf> <http://purl.org/np/RANAxL2OxGmP9VAN6cUi_0KEK0rJb9bPn4l1A5HquXKrI> ;
    nt:wasCreatedFromProvenanceTemplate <http://purl.org/np/RANwQa4ICWS5SOjw7gp99nBpXBasapwtZF1fIM3H2gYTM> ;
    nt:wasCreatedFromPubinfoTemplate <http://purl.org/np/RAA2MfqdBCzmz9yVWjKLXNbyfBNcwsMmOqcNUxkk1maIM> ,
<http://purl.org/np/RAOGu9Lh0BD4tbIRB9RG6RGRA_ObDh75NTbIqaWgxxs8M> ,
<http://purl.org/np/RAjpBMlw3owYhJUBo3DtsuDlXsNAJ8cnGeWAutDVjuAuI> ;
    nt:wasCreatedFromTemplate <http://purl.org/np/RAdpgRpigXtt8iPV9uOPf3wIT3qzOI8Sg2Q72CNV8g-Yo> .
}

This is the class definition of “expression of genes IRX3 and IRX5”:

@prefix this: <http://purl.org/np/RAwkXiTv7qCtqOYzlR6ozZRGLRtG6mlogrYdRQ1E4dRDg> .
@prefix sub: <http://purl.org/np/RAwkXiTv7qCtqOYzlR6ozZRGLRtG6mlogrYdRQ1E4dRDg#> .
@prefix np: <http://www.nanopub.org/nschema#> .
@prefix dct: <http://purl.org/dc/terms/> .
@prefix nt: <https://w3id.org/np/o/ntemplate/> .
@prefix npx: <http://purl.org/nanopub/x/> .
@prefix xsd: <http://www.w3.org/2001/XMLSchema#> .
@prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> .
@prefix orcid: <https://orcid.org/> .
@prefix prov: <http://www.w3.org/ns/prov#> .
@prefix skos: <http://www.w3.org/2004/02/skos/core#> .

sub:Head {
  this: np:hasAssertion sub:assertion ;
     np:hasProvenance sub:provenance ;
     np:hasPublicationInfo sub:pubinfo ;
     a np:Nanopublication .
}
sub:assertion {
  sub:expression-of-genes-IRX3-and-IRX5 a <http://www.w3.org/2002/07/owl#Class> ;
    rdfs:label "expression of genes IRX3 and IRX5" ;
    rdfs:subClassOf <http://www.wikidata.org/entity/Q26972> ;
    skos:definition "Expression of the human genes IRX3 and IRX5" ;
    skos:relatedMatch <http://www.wikidata.org/entity/Q18035174> , <http://www.wikidata.org/entity/Q18046058> .
}
sub:provenance {
  sub:assertion prov:wasAttributedTo orcid:0000-0003-2432-4125 .
}
sub:pubinfo {
  sub:sig npx:hasAlgorithm "RSA" ;
    npx:hasPublicKey
"MIGfMA0GCSqGSIb3DQEBAQUAA4GNADCBiQKBgQCS1s1OiABv1mrDnFWp9ecwHdQ+UlJn6JCDYXspRsbZgsm2QAiofbnVvf6gfkcjjScd5fq3sW/W8r/
o7bdafVSd6xuTG/vHrO9Ax/guPiJ6O/Z57Hk0nQy6c+l71HpaJ2BPPWKOgYiFZ/8eulmuM6BJ8TDKxoBtcqP5QbvN9KYjlQIDAQAB" ;
    npx:hasSignature
"kT9nlq5nE5y03RkSemozwUYzyNGdKTIPvY7WlWiDD2ZlRrHlOxQPbq+VPMEV6Ay3oEgTi/WuE5o6AY+dGK4V6eLcVnDQ1xqC7GsnaD5JGL89a5Z/
oEkHf1JG8fHQFOATrg4n62hcjGeRZOZrZLjdnAozGdDQf19gxq78E4QTyOY=" ;
    npx:hasSignatureTarget this: .
  this: dct:created "2021-10-27T09:44:46.276-07:00"^^xsd:dateTime ;
    dct:creator orcid:0000-0003-2432-4125 ;
    npx:introduces sub:expression-of-genes-IRX3-and-IRX5 ;
    npx:supersedes <http://purl.org/np/RANjcIDg1VkGWDSqxkFyVn__2UEbR-V7y8lqtV4rxcLJk> ;
    <https://w3id.org/linkflows/reviews/isUpdateOf>
    <http://purl.org/np/RAY3LaUoVtBLj9CN36wyyvTIjSMsACErVtEApnA12zjy0> ;
    nt:wasCreatedFromProvenanceTemplate <http://purl.org/np/RANwQa4ICWS5SOjw7gp99nBpXBasapwtZF1fIM3H2gYTM> ;
    nt:wasCreatedFromPubinfoTemplate <http://purl.org/np/RA2vCBXZf-icEcVRGhulJXugTGxpsV5yVr9yqCI1bQh4A> ,
    <http://purl.org/np/RAA2MfqdBCzmz9yVWjKLXNbyfBNcwsMmOqcNUxkk1maIM> ,
    <http://purl.org/np/RAjpBMlw3owYhJUBo3DtsuDlXsNAJ8cnGeWAutDVjuAuI> ;
    nt:wasCreatedFromTemplate <http://purl.org/np/RAdpgRpigXtt8iPV9uOPf3wIT3qzOI8Sg2Q72CNV8g-Yo> .
}

References

[1] 

M. Claussnitzer, S.N. Dankel, K.-H. Kim, G. Quon, W. Meuleman, C. Haugen, V. Glunk, I.S. Sousa, J.L. Beaudry, V. Puviindran, N.A. Abdennur, J. Liu, P.-A. Svensson, Y.-H. Hsu, D.J. Drucker, G. Mellgren, C.-C. Hui, H. Hauner and M. Kellis, FTO Obesity Variant Circuitry and Adipocyte Browning in Humans, New England Journal of Medicine 373: (10) ((2015) ), 895–907. doi:10.1056/NEJMoa1502214.

[2] 

C.I. Bucur, T. Kuhn, D. Ceolin and J. van Ossenbruggen, Expressing high-level scientific claims with formal semantics, in: Proceedings of the 11th Knowledge Capture Conference 2021. doi:10.1145/3460210.3493561.

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