diff --git a/src/model/hint.js b/src/model/hint.js index 5a3e3445..bc65e6e4 100644 --- a/src/model/hint.js +++ b/src/model/hint.js @@ -1,85 +1,84 @@ import _ from 'lodash'; +// Define constants for Hint types, combining ORGANISM with ENTITY_TYPE const HINT_TYPE = Object.freeze({ - ORGANISM: 'organism' + ORGANISM: 'organism', }); + +// Flatten the HINT_TYPE object to create an array of all hint types const HINT_TYPES = _.flatMap(HINT_TYPE); -const PASSAGE_TYPE = Object.freeze({ - TITLE: 'title', - ABSTRACT: 'abstract' +// Define constants for sections of a document +const SECTION = Object.freeze({ + TITLE: 'title', + ABSTRACT: 'abstract', }); -const PASSAGE_TYPES = _.flatMap(PASSAGE_TYPE); -/* -* Class representing a Hint. -* A hint is a piece of information that is extracted from sections of articles, such as the title or abstract. -* It can be about the organism being studied in the article or a gene name under investigation. -*/ -class Hint{ +// Flatten the SECTION object to create an array of all sections +const SECTIONS = _.flatMap(SECTION); - /** - * Create a Hint. - * @param {string} text - The hint text. - * @param {string} type - The hint type. - * @param {Object} xref - The hint xref. - * @param {string} section - The hint section. - */ - constructor(text, type, xref, section){ - this._text = text; - this._type = type; - this._xref = xref; - this._section = section; - } +/** + * Representing a bioentity mention and ground + */ +class Hint { + /** + * Creates an instance of Hint. + * @param {Array} param.texts - The texts associated with the hint. + * @param {string} param.type - The type of the hint. + * @param {Object} param.xref - The cross-reference (xref) object. + * @param {string} param.section - The section of the document where the hint was found. + */ + constructor(texts, type, xref, section) { + // Initialize the properties using the setters to enforce validation + this._texts = texts; + this._type = type; + this._xref = xref; + this._section = section; + } - /** - * Get the hint text. - * The text is a single mention extracted from the article section. - * @returns {string} The hint text. - */ - get text(){ - return this._text; - } + // Getter and setter for texts + get texts() { + return this._texts; + } - set text(value){ - this._text = value; - } + set texts(val) { + // Validate that texts is not empty + if (!val || _.isEmpty(val)) throw new TypeError('Invalid texts'); + this._texts = val; + } - get type(){ - return this._type; - } + // Getter and setter for type + get type() { + return this._type; + } - set type(value){ - if( value != HINT_TYPES.ORGANISM){ - throw new TypeError('Invalid type' + value); - } - this._type = value; - } + set type(val) { + // Validate that type is one of the predefined HINT_TYPES + if (!_.includes(HINT_TYPES, val)) throw new TypeError('Invalid type'); + this._type = val; + } - get xref(){ - return this._xref; - } + // Getter and setter for xref + get xref() { + return this._xref; + } - set xref(value){ - if (!value.dbPrefix || !value.id){ - throw new TypeError('Invalid xref' + JSON.stringify(value)); - } - this._xref = value; - } + set xref(val) { + // Validate that xref has dbPrefix and id properties + if (!val.dbPrefix || !val.id) throw new TypeError('Invalid xref'); + this._xref = val; + } - get section(){ - return this._section; - } + // Getter and setter for section + get section() { + return this._section; + } - set section(value){ - if( ! _.includes(PASSAGE_TYPES, value) ) { - throw new TypeError('Invalid section' + value); - } - this._section = value; - } + set section(val) { + // Validate that section is one of the predefined SECTIONS + if (!_.includes(SECTIONS, val)) throw new TypeError('Invalid section'); + this._section = val; + } } -export { - Hint, - HINT_TYPE, - PASSAGE_TYPE -}; + +export { Hint, HINT_TYPE, SECTION }; diff --git a/src/server/routes/api/document/hint/pubtator.js b/src/server/routes/api/document/hint/pubtator.js new file mode 100644 index 00000000..f12f4f18 --- /dev/null +++ b/src/server/routes/api/document/hint/pubtator.js @@ -0,0 +1,163 @@ +import _ from 'lodash'; +import { Hint, HINT_TYPE } from '../../../../../model/hint.js'; +import { COLLECTIONS } from '../../../../../util/registry.js'; + +/** + * Map a PubTator BioCDocument to a hint + * @param {object} bioCDocument as defined by [NLM DTD]{@link ftp://ftp.ncbi.nlm.nih.gov/pub/wilbur/BioC-PMC/BioC.dtd} + * @returns {Array.} hints a set of hints + */ +function map(bioCDocument) { + let hints = []; + + // See Table 1 https://www.ncbi.nlm.nih.gov/research/pubtator3/tutorial + const PUBTATOR_ANNOTATION_TYPE = Object.freeze({ + SPECIES: 'Species', + // could add more types here when scope expands + }); + const PUBTATOR_DATABASE = Object.freeze({ + ncbi_taxonomy: 'ncbi_taxonomy', + // could add more databases here when scope expands + }); + const entityTypes = new Map([ + [PUBTATOR_ANNOTATION_TYPE.SPECIES, HINT_TYPE.ORGANISM], + ]); + const database2Xref = new Map([ + [PUBTATOR_DATABASE.ncbi_taxonomy, COLLECTIONS.NCBI_TAXONOMY], + ]); + + /** + * Checks if the type of a given annotation is valid based on a predefined list of valid types. + * + * This function extracts the `type` field from the `infons` object of an annotation + * and checks if this type is included in the `PUBTATOR_ANNOTATION_TYPE` array. + * + * @param {Object} annotation - An annotation object containing an `infons` object with metadata. + * @returns {boolean} - Returns `true` if the `type` of the annotation is included in `PUBTATOR_ANNOTATION_TYPE`, otherwise `false`. + */ + const isValidType = (annotation) => { + const { + infons: { type }, + } = annotation; + return _.includes(PUBTATOR_ANNOTATION_TYPE, type); + }; + + /** + * Checks if the xref (cross-reference) of a given annotation is valid. + * + * This function performs a series of checks on the `identifier` field within the `infons` object of an annotation + * to determine its validity. It checks for the presence of an identifier, ensures it is not null or undefined, + * ensures it is not an empty string or a dash, and checks that it is not a semi-colon delimited string. + * + * @param {Object} annotation - An annotation object containing an `infons` object with metadata. + * @returns {boolean} - Returns `true` if the `identifier` of the annotation passes all validation checks, otherwise `false`. + * + * Validation Checks: + * - The `identifier` must exist. + * - The `identifier` must not be null or undefined. + * - The `identifier` must not be an empty string or a dash ('-'). + * - The `identifier` must not be a semi-colon delimited string. + */ + const isValidXref = (annotation) => { + const EMPTY_SYMBOLS = new Set(['-', '']); + let isValid = false; + // Check if there is an identifier + const hasId = (a) => _.has(a, ['infons', 'identifier']); + // Check if the identifier value is null or undefined + const isNil = (a) => { + const id = _.get(a, ['infons', 'identifier']); + return _.isNil(id); + }; + // Check if the identifier value is empty or a dash + const isEmpty = (a) => { + const id = _.get(a, ['infons', 'identifier']); + return EMPTY_SYMBOLS.has(id); + }; + // Check if the identifier value is semi-colon delimited + const isSemiColonDelimited = (a) => { + const id = _.get(a, ['infons', 'identifier']); + const ids = _.compact(id.split(';')); + return ids.length > 1; + }; + if ( + hasId(annotation) && + !isNil(annotation) && + !isEmpty(annotation) && + !isSemiColonDelimited(annotation) + ) { + isValid = true; + } + return isValid; + }; + + /** + * Groups a list of annotation objects by their database and identifier (xref) fields. + * + * This function processes an array of annotations, grouping them based on a composite key + * created from the `database` and `identifier` fields in the `infons` object of each annotation. + * After grouping, it transforms each group into an object containing the `infons` from the first + * annotation in the group and an array of all `text` fields from the annotations in that group. + * + * @param {Array} annotations - An array of annotation objects, each containing an `infons` object with metadata and a `text` field. + * @returns {Array} - An array of objects, where each object contains: + * - `infons`: The metadata from the first annotation in the group. + * - `texts`: An array of `text` fields from all annotations in the group. + * + */ + const groupByXref = (annotations) => { + const byXref = ({ infons }) => `${infons.database}_${infons.identifier}`; + let groups = _.groupBy(annotations, byXref); + groups = Object.values(groups).map((group) => { + const texts = group.map((a) => a.text); + const first = _.first(group); + const core = _.pick(first, ['infons']); + return _.assign(core, { texts }); + }); + return groups; + }; + + /** + * Converts an annotation object into a Hint object. + * + * This function extracts relevant fields from an annotation object and constructs a new Hint object. + * It retrieves the identifier, database, and type from the `infons` object of the annotation, maps the database to an xref, + * and maps the type to an entity type. It then creates a new Hint object using these extracted and mapped values, along with the provided section. + * + * @param {Object} annotation - An annotation object containing `infons` and `texts` fields. + * @param {string} section - A string representing the section of the document where the annotation was found. e.g., 'title' or 'abstract'. + * @returns {Hint} - Returns a new Hint object constructed from the annotation data and section. + */ + const toHint = (annotation, section) => { + // Destructure the relevant fields from the annotation + const { + texts, + infons: { identifier: id, database, type }, + } = annotation; + // Assign the id, dbName, and dbPrefix to an xref object + const xref = _.assign({ id }, database2Xref.get(database)); + // Map the type to an entity type + const eType = entityTypes.get(type); + // Create a new Hint object with the extracted and mapped values + const hint = new Hint(texts, eType, xref, section); + + return hint; + }; + + let { passages } = bioCDocument; + + for (const passage of passages) { + let { annotations } = passage; + const section = passage.infons.type; + annotations = _.filter(annotations, isValidType); + annotations = _.filter(annotations, isValidXref); + annotations = groupByXref(annotations); + + annotations.forEach((a) => { + const hint = toHint(a, section); + hints.push(hint); + }); + } + return hints; +} + +export default map; diff --git a/src/util/registry.js b/src/util/registry.js new file mode 100644 index 00000000..628714c9 --- /dev/null +++ b/src/util/registry.js @@ -0,0 +1,17 @@ +const COLLECTIONS = Object.freeze({ + PUBMED: { + dbname: 'PubMed', + dbPrefix: 'pubmed' + }, + /** + * The Taxonomy Database is a curated classification and nomenclature for all of the organisms + * in the public sequence databases. This currently represents about 10% of the described species of life on the planet. + */ + NCBI_TAXONOMY: { + dbname: 'NCBI Taxonomy', + dbPrefix: 'NCBITaxon' + } +}); + +export { COLLECTIONS }; + diff --git a/test/pubtator/10.1016_j.molcel.2019.03.023.json b/test/pubtator/10.1016_j.molcel.2019.03.023.json index dc842a33..0ef4248a 100644 --- a/test/pubtator/10.1016_j.molcel.2019.03.023.json +++ b/test/pubtator/10.1016_j.molcel.2019.03.023.json @@ -1,536 +1,494 @@ { - "_id": "31003867|None", - "id": "10.1016/j.molcel.2019.03.023", - "infons": { - "doi": "10.1016/j.molcel.2019.03.023", - "comment": "M. Musculus orthologues: ANKRD31, REC114" - }, - "passages": [ - { - "infons": { - "journal": "Mol Cell. 2019 Jun 6;74(5):1053-1068.e8. doi: 10.1016/j.molcel.2019.03.023. Epub ", - "year": "2019", - "article-id_pmc": "PMC6555648", - "type": "title", - "authors": "Boekhout M, Karasu ME, Wang J, Acquaviva L, Pratto F, Brick K, Eng DY, Xu J, Camerini-Otero RD, Patel DJ, Keeney S" - }, - "offset": 0, - "text": "REC114 Partner ANKRD31 Controls Number, Timing, and Location of Meiotic DNA Breaks.", - "sentences": [], - "annotations": [ - { - "id": "2", - "infons": { - "identifier": "73673", - "type": "Gene", - "ncbi_homologene": "83546", - "valid": true, - "normalized": [ - 73673 - ], - "database": "ncbi_gene", - "normalized_id": 73673, - "biotype": "gene", - "name": "Rec114", - "accession": "@GENE_REC114" - }, - "text": "REC114", - "locations": [ - { - "offset": 0, - "length": 6 - } - ] - }, - { - "id": "3", - "infons": { - "identifier": "625662", - "type": "Gene", - "ncbi_homologene": "110355", - "valid": true, - "normalized": [ - 625662 - ], - "database": "ncbi_gene", - "normalized_id": 625662, - "biotype": "gene", - "name": "Ankrd31", - "accession": "@GENE_ANKRD31" - }, - "text": "ANKRD31", - "locations": [ - { - "offset": 15, - "length": 7 - } - ] - } - ], - "relations": [] + "_id": "31003867|None", + "id": "10.1016/j.molcel.2019.03.023", + "infons": { + "doi": "10.1016/j.molcel.2019.03.023", + "comment": "M. Musculus orthologues: ANKRD31, REC114" + }, + "passages": [ + { + "infons": { + "journal": "Mol Cell. 2019 Jun 6;74(5):1053-1068.e8. doi: 10.1016/j.molcel.2019.03.023. Epub ", + "year": "2019", + "article-id_pmc": "PMC6555648", + "type": "title", + "authors": "Boekhout M, Karasu ME, Wang J, Acquaviva L, Pratto F, Brick K, Eng DY, Xu J, Camerini-Otero RD, Patel DJ, Keeney S" }, - { - "infons": { - "type": "abstract" - }, - "offset": 84, - "text": "Double-strand breaks (DSBs) initiate the homologous recombination that is crucial for meiotic chromosome pairing and segregation. Here, we unveil mouse ANKRD31 as a lynchpin governing multiple aspects of DSB formation. Spermatocytes lacking ANKRD31 have altered DSB locations and fail to target DSBs to the pseudoautosomal regions (PARs) of sex chromosomes. They also have delayed and/or fewer recombination sites but, paradoxically, more DSBs, suggesting DSB dysregulation. Unrepaired DSBs and pairing failures-stochastic on autosomes, nearly absolute on X and Y-cause meiotic arrest and sterility in males. Ankrd31-deficient females have reduced oocyte reserves. A crystal structure defines a pleckstrin homology (PH) domain in REC114 and its direct intermolecular contacts with ANKRD31. In vivo, ANKRD31 stabilizes REC114 association with the PAR and elsewhere. Our findings inform a model in which ANKRD31 is a scaffold anchoring REC114 and other factors to specific genomic locations, thereby regulating DSB formation.", - "sentences": [], - "annotations": [ - { - "id": "15", - "infons": { - "identifier": "10090", - "type": "Species", - "valid": true, - "normalized": [ - 10090 - ], - "database": "ncbi_taxonomy", - "normalized_id": 10090, - "biotype": "species", - "name": "10090", - "accession": null - }, - "text": "mouse", - "locations": [ - { - "offset": 230, - "length": 5 - } - ] - }, - { - "id": "16", - "infons": { - "identifier": "625662", - "type": "Gene", - "ncbi_homologene": "110355", - "valid": true, - "normalized": [ - 625662 - ], - "database": "ncbi_gene", - "normalized_id": 625662, - "biotype": "gene", - "name": "Ankrd31", - "accession": "@GENE_ANKRD31" - }, - "text": "ANKRD31", - "locations": [ - { - "offset": 236, - "length": 7 - } - ] - }, - { - "id": "17", - "infons": { - "identifier": "625662", - "type": "Gene", - "ncbi_homologene": "110355", - "valid": true, - "normalized": [ - 625662 - ], - "database": "ncbi_gene", - "normalized_id": 625662, - "biotype": "gene", - "name": "Ankrd31", - "accession": "@GENE_ANKRD31" - }, - "text": "ANKRD31", - "locations": [ - { - "offset": 325, - "length": 7 - } - ] - }, - { - "id": "18", - "infons": { - "identifier": "MESH:D007246", - "type": "Disease", - "valid": true, - "normalized": [ - "D007246" - ], - "database": "ncbi_mesh", - "normalized_id": "D007246", - "biotype": "disease", - "name": "Infertility", - "accession": "@DISEASE_Infertility" - }, - "text": "sterility", - "locations": [ - { - "offset": 673, - "length": 9 - } - ] - }, - { - "id": "19", - "infons": { - "identifier": "73673", - "type": "Gene", - "ncbi_homologene": "83546", - "valid": true, - "normalized": [ - 73673 - ], - "database": "ncbi_gene", - "normalized_id": 73673, - "biotype": "gene", - "name": "Rec114", - "accession": "@GENE_REC114" - }, - "text": "REC114", - "locations": [ - { - "offset": 814, - "length": 6 - } - ] - }, - { - "id": "20", - "infons": { - "identifier": "625662", - "type": "Gene", - "ncbi_homologene": "110355", - "valid": true, - "normalized": [ - 625662 - ], - "database": "ncbi_gene", - "normalized_id": 625662, - "biotype": "gene", - "name": "Ankrd31", - "accession": "@GENE_ANKRD31" - }, - "text": "ANKRD31", - "locations": [ - { - "offset": 865, - "length": 7 - } - ] + "offset": 0, + "text": "REC114 Partner ANKRD31 Controls Number, Timing, and Location of Meiotic DNA Breaks.", + "sentences": [], + "annotations": [ + { + "id": "2", + "infons": { + "identifier": "73673", + "type": "Gene", + "ncbi_homologene": "83546", + "valid": true, + "normalized": [73673], + "database": "ncbi_gene", + "normalized_id": 73673, + "biotype": "gene", + "name": "Rec114", + "accession": "@GENE_REC114" }, - { - "id": "21", - "infons": { - "identifier": "625662", - "type": "Gene", - "ncbi_homologene": "110355", - "valid": true, - "normalized": [ - 625662 - ], - "database": "ncbi_gene", - "normalized_id": 625662, - "biotype": "gene", - "name": "Ankrd31", - "accession": "@GENE_ANKRD31" - }, - "text": "ANKRD31", - "locations": [ - { - "offset": 883, - "length": 7 - } - ] + "text": "REC114", + "locations": [ + { + "offset": 0, + "length": 6 + } + ] + }, + { + "id": "3", + "infons": { + "identifier": "625662", + "type": "Gene", + "ncbi_homologene": "110355", + "valid": true, + "normalized": [625662], + "database": "ncbi_gene", + "normalized_id": 625662, + "biotype": "gene", + "name": "Ankrd31", + "accession": "@GENE_ANKRD31" }, - { - "id": "22", - "infons": { - "identifier": "73673", - "type": "Gene", - "ncbi_homologene": "83546", - "valid": true, - "normalized": [ - 73673 - ], - "database": "ncbi_gene", - "normalized_id": 73673, - "biotype": "gene", - "name": "Rec114", - "accession": "@GENE_REC114" - }, - "text": "REC114", - "locations": [ - { - "offset": 902, - "length": 6 - } - ] + "text": "ANKRD31", + "locations": [ + { + "offset": 15, + "length": 7 + } + ] + } + ], + "relations": [] + }, + { + "infons": { + "type": "abstract" + }, + "offset": 84, + "text": "Double-strand breaks (DSBs) initiate the homologous recombination that is crucial for meiotic chromosome pairing and segregation. Here, we unveil mouse ANKRD31 as a lynchpin governing multiple aspects of DSB formation. Spermatocytes lacking ANKRD31 have altered DSB locations and fail to target DSBs to the pseudoautosomal regions (PARs) of sex chromosomes. They also have delayed and/or fewer recombination sites but, paradoxically, more DSBs, suggesting DSB dysregulation. Unrepaired DSBs and pairing failures-stochastic on autosomes, nearly absolute on X and Y-cause meiotic arrest and sterility in males. Ankrd31-deficient females have reduced oocyte reserves. A crystal structure defines a pleckstrin homology (PH) domain in REC114 and its direct intermolecular contacts with ANKRD31. In vivo, ANKRD31 stabilizes REC114 association with the PAR and elsewhere. Our findings inform a model in which ANKRD31 is a scaffold anchoring REC114 and other factors to specific genomic locations, thereby regulating DSB formation.", + "sentences": [], + "annotations": [ + { + "id": "15", + "infons": { + "identifier": "10090", + "type": "Species", + "valid": true, + "normalized": [10090], + "database": "ncbi_taxonomy", + "normalized_id": 10090, + "biotype": "species", + "name": "10090", + "accession": null }, - { - "id": "23", - "infons": { - "identifier": "69597", - "type": "Gene", - "ncbi_homologene": "4947", - "valid": true, - "normalized": [ - 69597 - ], - "database": "ncbi_gene", - "normalized_id": 69597, - "biotype": "gene", - "name": "Afg3l2", - "accession": "@GENE_AFG3L2" - }, - "text": "PAR", - "locations": [ - { - "offset": 930, - "length": 3 - } - ] + "text": "mouse", + "locations": [ + { + "offset": 230, + "length": 5 + } + ] + }, + { + "id": "16", + "infons": { + "identifier": "625662", + "type": "Gene", + "ncbi_homologene": "110355", + "valid": true, + "normalized": [625662], + "database": "ncbi_gene", + "normalized_id": 625662, + "biotype": "gene", + "name": "Ankrd31", + "accession": "@GENE_ANKRD31" }, - { - "id": "24", - "infons": { - "identifier": "625662", - "type": "Gene", - "ncbi_homologene": "110355", - "valid": true, - "normalized": [ - 625662 - ], - "database": "ncbi_gene", - "normalized_id": 625662, - "biotype": "gene", - "name": "Ankrd31", - "accession": "@GENE_ANKRD31" - }, - "text": "ANKRD31", - "locations": [ - { - "offset": 986, - "length": 7 - } - ] + "text": "ANKRD31", + "locations": [ + { + "offset": 236, + "length": 7 + } + ] + }, + { + "id": "17", + "infons": { + "identifier": "625662", + "type": "Gene", + "ncbi_homologene": "110355", + "valid": true, + "normalized": [625662], + "database": "ncbi_gene", + "normalized_id": 625662, + "biotype": "gene", + "name": "Ankrd31", + "accession": "@GENE_ANKRD31" }, - { - "id": "25", - "infons": { - "identifier": "73673", - "type": "Gene", - "ncbi_homologene": "83546", - "valid": true, - "normalized": [ - 73673 - ], - "database": "ncbi_gene", - "normalized_id": 73673, - "biotype": "gene", - "name": "Rec114", - "accession": "@GENE_REC114" - }, - "text": "REC114", - "locations": [ - { - "offset": 1018, - "length": 6 - } - ] - } - ], - "relations": [] - } - ], - "relations": [ - { - "id": "R1", - "infons": { - "score": "0.9995", - "role1": { + "text": "ANKRD31", + "locations": [ + { + "offset": 325, + "length": 7 + } + ] + }, + { + "id": "18", + "infons": { "identifier": "MESH:D007246", "type": "Disease", "valid": true, - "normalized": [ - "D007246" - ], + "normalized": ["D007246"], "database": "ncbi_mesh", "normalized_id": "D007246", "biotype": "disease", "name": "Infertility", "accession": "@DISEASE_Infertility" }, - "role2": { + "text": "sterility", + "locations": [ + { + "offset": 673, + "length": 9 + } + ] + }, + { + "id": "19", + "infons": { + "identifier": "73673", + "type": "Gene", + "ncbi_homologene": "83546", + "valid": true, + "normalized": [73673], + "database": "ncbi_gene", + "normalized_id": 73673, + "biotype": "gene", + "name": "Rec114", + "accession": "@GENE_REC114" + }, + "text": "REC114", + "locations": [ + { + "offset": 814, + "length": 6 + } + ] + }, + { + "id": "20", + "infons": { "identifier": "625662", "type": "Gene", + "ncbi_homologene": "110355", "valid": true, - "normalized": [ - 625662 - ], + "normalized": [625662], "database": "ncbi_gene", "normalized_id": 625662, "biotype": "gene", "name": "Ankrd31", "accession": "@GENE_ANKRD31" }, - "type": "Association" + "text": "ANKRD31", + "locations": [ + { + "offset": 865, + "length": 7 + } + ] }, - "nodes": [ - { - "refid": "0", - "role": "5,4" - } - ] - }, - { - "id": "R2", - "infons": { - "score": "0.9555", - "role1": { + { + "id": "21", + "infons": { "identifier": "625662", "type": "Gene", + "ncbi_homologene": "110355", "valid": true, - "normalized": [ - 625662 - ], + "normalized": [625662], "database": "ncbi_gene", "normalized_id": 625662, "biotype": "gene", "name": "Ankrd31", "accession": "@GENE_ANKRD31" }, - "role2": { + "text": "ANKRD31", + "locations": [ + { + "offset": 883, + "length": 7 + } + ] + }, + { + "id": "22", + "infons": { "identifier": "73673", "type": "Gene", + "ncbi_homologene": "83546", "valid": true, - "normalized": [ - 73673 - ], + "normalized": [73673], "database": "ncbi_gene", "normalized_id": 73673, "biotype": "gene", "name": "Rec114", "accession": "@GENE_REC114" }, - 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{ - "name": "associate|@GENE_AFG3L2|@GENE_REC114" + "nodes": [ + { + "refid": "1", + "role": "1,0" + } + ] + }, + { + "id": "R3", + "infons": { + "score": "0.4854", + "role1": { + "identifier": "69597", + "type": "Gene", + "valid": true, + "normalized": [69597], + "database": "ncbi_gene", + "normalized_id": 69597, + "biotype": "gene", + "name": "Afg3l2", + "accession": "@GENE_AFG3L2" + }, + "role2": { + "identifier": "73673", + "type": "Gene", + "valid": true, + "normalized": [73673], + "database": "ncbi_gene", + "normalized_id": 73673, + "biotype": "gene", + "name": "Rec114", + "accession": "@GENE_REC114" + }, + "type": "Association" }, - { - "name": "associate|@GENE_ANKRD31|@GENE_AFG3L2" - } - ] - } \ No newline at end of file + "nodes": [ + { + "refid": "2", + "role": "10,9" + } + ] + }, + { + "id": "R4", + "infons": { + "score": "0.9952", + "role1": { + "identifier": "625662", + "type": "Gene", + "valid": true, + "normalized": [625662], + "database": "ncbi_gene", + "normalized_id": 625662, + "biotype": "gene", + "name": "Ankrd31", + "accession": "@GENE_ANKRD31" + }, + "role2": { + "identifier": "69597", + "type": "Gene", + "valid": true, + "normalized": [69597], + "database": "ncbi_gene", + "normalized_id": 69597, + "biotype": "gene", + "name": "Afg3l2", + "accession": "@GENE_AFG3L2" + }, + "type": "Association" + }, + "nodes": [ + { + "refid": "3", + "role": "8,10" + } + ] + } + ], + "pmid": 31003867, + "pmcid": null, + "meta": {}, + "date": "2019-06-06T00:00:00Z", + "journal": "Mol Cell", + "authors": [ + "Boekhout M", + "Karasu ME", + "Wang J", + "Acquaviva L", + "Pratto F", + "Brick K", + "Eng DY", + "Xu J", + "Camerini-Otero RD", + "Patel DJ", + "Keeney S" + ], + "relations_display": [ + { + "name": "associate|@DISEASE_Infertility|@GENE_ANKRD31" + }, + { + "name": "associate|@GENE_ANKRD31|@GENE_REC114" + }, + { + "name": "associate|@GENE_AFG3L2|@GENE_REC114" + }, + { + "name": "associate|@GENE_ANKRD31|@GENE_AFG3L2" + } + ] +} diff --git a/test/pubtator/10.1016_j.molcel.2024.01.007.json b/test/pubtator/10.1016_j.molcel.2024.01.007.json deleted file mode 100644 index b837a397..00000000 --- a/test/pubtator/10.1016_j.molcel.2024.01.007.json +++ /dev/null @@ -1,497 +0,0 @@ -{ - "_id": "38309274|None", - "id": "10.1016/j.molcel.2024.01.007", - "infons": { - "doi": "10.1016/j.molcel.2024.01.007", - "comment": "Get: Missing IκBζ; mapping greek symbol" - }, - "passages": [ - { - "infons": { - "journal": "Mol Cell;2024Jan24. doi:10.1016/j.molcel.2024.01.007", - "year": "2024", - "type": "title", - "authors": "Alpsoy A, Wu XS, Pal S, Klingbeil O, Kumar P, El Demerdash O, Nalbant B, Vakoc CR, " - }, - "offset": 0, - "text": "IkappaBzeta is a dual-use coactivator of NF-kappaB and POU transcription factors.", - "sentences": [], - "annotations": [ - { - "id": "2", - "infons": { - "identifier": "64332", - "type": "Gene", - "ncbi_homologene": "12734", - "valid": true, - "normalized": [ - 64332 - ], - "database": "ncbi_gene", - "normalized_id": 64332, - "biotype": "gene", - "name": "NFKBIZ", - "accession": "@GENE_NFKBIZ" - }, - "text": "IkappaBzeta", - "locations": [ - { - "offset": 0, - "length": 11 - } - ] - }, - { - "id": "3", - "infons": { - "identifier": "4790", - "type": "Gene", - "ncbi_homologene": "2971", - "valid": true, - "normalized": [ - 4790 - ], - "database": "ncbi_gene", - "normalized_id": 4790, - "biotype": "gene", - "name": "NFKB1", - "accession": "@GENE_NFKB1" - }, - "text": "NF-kappaB", - "locations": [ - { - "offset": 41, - "length": 9 - } - ] - } - ], - "relations": [] - }, - { - "infons": { - "type": "abstract" - }, - "offset": 82, - "text": "OCA-B, OCA-T1, and OCA-T2 belong to a family of coactivators that bind to POU transcription factors (TFs) to regulate gene expression in immune cells. Here, we identify IkappaBzeta (encoded by the NFKBIZ gene) as an additional coactivator of POU TFs. Although originally discovered as an inducible regulator of NF-kappaB, we show here that IkappaBzeta shares a microhomology with OCA proteins and uses this segment to bind to POU TFs and octamer-motif-containing DNA. Our functional experiments suggest that IkappaBzeta requires its interaction with POU TFs to coactivate immune-related genes. This finding is reinforced by epigenomic analysis of MYD88L265P-mutant lymphoma cells, which revealed colocalization of IkappaBzeta with the POU TF OCT2 and NF-kappaB:p50 at hundreds of DNA elements harboring octamer and kappaB motifs. These results suggest that IkappaBzeta is a transcriptional coactivator that can amplify and integrate the output of NF-kappaB and POU TFs at inducible genes in immune cells.", - "sentences": [], - "annotations": [ - { - "id": "17", - "infons": { - "identifier": "5450", - "type": "Gene", - "ncbi_homologene": "4543", - "valid": true, - "normalized": [ - 5450 - ], - "database": "ncbi_gene", - "normalized_id": 5450, - "biotype": "gene", - "name": "POU2AF1", - "accession": "@GENE_POU2AF1" - }, - "text": "OCA-B", - "locations": [ - { - "offset": 82, - "length": 5 - } - ] - }, - { - "id": "18", - "infons": { - "identifier": "64332", - "type": "Gene", - "ncbi_homologene": "12734", - "valid": true, - "normalized": [ - 64332 - ], - "database": "ncbi_gene", - "normalized_id": 64332, - "biotype": "gene", - "name": "NFKBIZ", - "accession": "@GENE_NFKBIZ" - }, - "text": "IkappaBzeta", - "locations": [ - { - "offset": 251, - "length": 11 - } - ] - }, - { - "id": "19", - "infons": { - "identifier": "64332", - "type": "Gene", - "ncbi_homologene": "12734", - "valid": true, - "normalized": [ - 64332 - ], - "database": "ncbi_gene", - "normalized_id": 64332, - "biotype": "gene", - "name": "NFKBIZ", - "accession": "@GENE_NFKBIZ" - }, - "text": "NFKBIZ", - "locations": [ - { - "offset": 279, - "length": 6 - } - ] - }, - { - "id": "20", - "infons": { - "identifier": "4790", - "type": "Gene", - "ncbi_homologene": "2971", - "valid": true, - "normalized": [ - 4790 - ], - "database": "ncbi_gene", - "normalized_id": 4790, - "biotype": "gene", - "name": "NFKB1", - "accession": "@GENE_NFKB1" - }, - "text": "NF-kappaB", - "locations": [ - { - "offset": 393, - "length": 9 - } - ] - }, - { - "id": "21", - "infons": { - "identifier": "64332", - "type": "Gene", - "ncbi_homologene": "12734", - "valid": true, - "normalized": [ - 64332 - ], - "database": "ncbi_gene", - "normalized_id": 64332, - "biotype": "gene", - "name": "NFKBIZ", - "accession": "@GENE_NFKBIZ" - }, - "text": "IkappaBzeta", - "locations": [ - { - "offset": 422, - "length": 11 - } - ] - }, - { - "id": "22", - "infons": { - "identifier": "64332", - "type": "Gene", - "ncbi_homologene": "12734", - "valid": true, - "normalized": [ - 64332 - ], - "database": "ncbi_gene", - "normalized_id": 64332, - "biotype": "gene", - "name": "NFKBIZ", - "accession": "@GENE_NFKBIZ" - }, - "text": "IkappaBzeta", - "locations": [ - { - "offset": 590, - "length": 11 - } - ] - }, - { - "id": "23", - "infons": { - "identifier": "MESH:D008223", - "type": "Disease", - "valid": true, - "normalized": [ - "D008223" - ], - "database": "ncbi_mesh", - "normalized_id": "D008223", - "biotype": "disease", - "name": "Lymphoma", - "accession": "@DISEASE_Lymphoma" - }, - "text": "lymphoma", - "locations": [ - { - "offset": 747, - "length": 8 - } - ] - }, - { - "id": "24", - "infons": { - "identifier": "64332", - "type": "Gene", - "ncbi_homologene": "12734", - "valid": true, - "normalized": [ - 64332 - ], - "database": "ncbi_gene", - "normalized_id": 64332, - "biotype": "gene", - "name": "NFKBIZ", - "accession": "@GENE_NFKBIZ" - }, - "text": "IkappaBzeta", - "locations": [ - { - "offset": 796, - "length": 11 - } - ] - }, - { - "id": "25", - "infons": { - "identifier": "5452", - "type": "Gene", - "ncbi_homologene": "55674", - "valid": true, - "normalized": [ - 5452 - ], - "database": "ncbi_gene", - "normalized_id": 5452, - "biotype": "gene", - "name": "POU2F2", - "accession": "@GENE_POU2F2" - }, - "text": "OCT2", - "locations": [ - { - "offset": 824, - "length": 4 - } - ] - }, - { - "id": "26", - "infons": { - "identifier": "4790", - "type": "Gene", - "ncbi_homologene": "2971", - "valid": true, - "normalized": [ - 4790 - ], - "database": "ncbi_gene", - "normalized_id": 4790, - "biotype": "gene", - "name": "NFKB1", - "accession": "@GENE_NFKB1" - }, - "text": "NF-kappaB", - "locations": [ - { - "offset": 833, - "length": 9 - } - ] - }, - { - "id": "27", - "infons": { - "identifier": "4790", - "type": "Gene", - "ncbi_homologene": "2971", - "valid": true, - "normalized": [ - 4790 - ], - "database": "ncbi_gene", - "normalized_id": 4790, - "biotype": "gene", - "name": "NFKB1", - "accession": "@GENE_NFKB1" - }, - "text": "p50", - "locations": [ - { - "offset": 843, - "length": 3 - } - ] - }, - { - "id": "28", - "infons": { - "identifier": "64332", - "type": "Gene", - "ncbi_homologene": "12734", - "valid": true, - "normalized": [ - 64332 - ], - "database": "ncbi_gene", - "normalized_id": 64332, - "biotype": "gene", - "name": "NFKBIZ", - "accession": "@GENE_NFKBIZ" - }, - "text": "IkappaBzeta", - "locations": [ - { - "offset": 939, - "length": 11 - } - ] - }, - { - "id": "29", - "infons": { - "identifier": "4790", - "type": "Gene", - "ncbi_homologene": "2971", - "valid": true, - "normalized": [ - 4790 - ], - "database": "ncbi_gene", - "normalized_id": 4790, - "biotype": "gene", - "name": "NFKB1", - "accession": "@GENE_NFKB1" - }, - "text": "NF-kappaB", - "locations": [ - { - "offset": 1029, - "length": 9 - } - ] - } - ], - "relations": [] - } - ], - "relations": [ - { - "id": "R1", - "infons": { - "score": "0.9989", - "role1": { - "identifier": "5452", - "type": "Gene", - "valid": true, - "normalized": [ - 5452 - ], - "database": "ncbi_gene", - "normalized_id": 5452, - "biotype": "gene", - "name": "POU2F2", - "accession": "@GENE_POU2F2" - }, - "role2": { - "identifier": "64332", - "type": "Gene", - "valid": true, - "normalized": [ - 64332 - ], - "database": "ncbi_gene", - "normalized_id": 64332, - "biotype": "gene", - "name": "NFKBIZ", - "accession": "@GENE_NFKBIZ" - }, - "type": "Association" - }, - "nodes": [ - { - "refid": "0", - "role": "10,9" - } - ] - }, - { - "id": "R2", - "infons": { - "score": "0.9979", - "role1": { - "identifier": "4790", - "type": "Gene", - "valid": true, - "normalized": [ - 4790 - ], - "database": "ncbi_gene", - "normalized_id": 4790, - "biotype": "gene", - "name": "NFKB1", - "accession": "@GENE_NFKB1" - }, - "role2": { - "identifier": "64332", - "type": "Gene", - "valid": true, - "normalized": [ - 64332 - ], - "database": "ncbi_gene", - "normalized_id": 64332, - "biotype": "gene", - "name": "NFKBIZ", - "accession": "@GENE_NFKBIZ" - }, - "type": "Positive_Correlation" - }, - "nodes": [ - { - "refid": "1", - "role": "1,0" - } - ] - } - ], - "pmid": 38309274, - "pmcid": null, - "meta": {}, - "date": "2024-01-24T00:00:00Z", - "journal": "Mol Cell", - "authors": [ - "Alpsoy A", - "Wu XS", - "Pal S", - "Klingbeil O", - "Kumar P", - "El Demerdash O", - "Nalbant B", - "Vakoc CR" - ], - "relations_display": [ - { - "name": "associate|@GENE_POU2F2|@GENE_NFKBIZ" - }, - { - "name": "positive_correlate|@GENE_NFKB1|@GENE_NFKBIZ" - } - ] - } \ No newline at end of file diff --git a/test/pubtator/10.1038_s41556-021-00642-9.json b/test/pubtator/10.1038_s41556-021-00642-9.json index 87a81787..3f6075a6 100644 --- a/test/pubtator/10.1038_s41556-021-00642-9.json +++ b/test/pubtator/10.1038_s41556-021-00642-9.json @@ -1,770 +1,698 @@ { - "_id": "33664495|None", - "id": "10.1038/s41556-021-00642-9", - "infons": { - "doi": "10.1038/s41556-021-00642-9", - "comment": "M. musculus orthologue: Aida, Ucp1" - }, - "passages": [ - { - "infons": { - "journal": "Nat Cell Biol. 2021 Mar;23(3):268-277. doi: 10.1038/s41556-021-00642-9. Epub 2021 ", - "year": "2021", - "type": "title", - "authors": "Shi M, Huang XY, Ren XY, Wei XY, Ma Y, Lin ZZ, Liu DT, Song L, Zhao TJ, Li G, Yao L, Zhu M, Zhang C, Xie C, Wu Y, Wu HM, Fan LP, Ou J, Zhan YH, Lin SY, Lin SC" - }, - "offset": 0, - "text": "AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1.", - "sentences": [], - "annotations": [ - { - "id": "2", - "infons": { - "identifier": "108909", - "type": "Gene", - "ncbi_homologene": "11268", - "valid": true, - "normalized": [ - 108909 - ], - "database": "ncbi_gene", - "normalized_id": 108909, - "biotype": "gene", - "name": "Aida", - "accession": "@GENE_AIDA" - }, - "text": "AIDA", - "locations": [ - { - "offset": 0, - "length": 4 - } - ] - }, - { - "id": "3", - "infons": { - "identifier": "22227", - "type": "Gene", - "ncbi_homologene": "22524", - "valid": true, - "normalized": [ - 22227 - ], - "database": "ncbi_gene", - "normalized_id": 22227, - "biotype": "gene", - "name": "Ucp1", - "accession": "@GENE_UCP1" - }, - "text": "UCP1", - "locations": [ - { - "offset": 76, - "length": 4 - } - ] - } - ], - "relations": [] + "_id": "33664495|None", + "id": "10.1038/s41556-021-00642-9", + "infons": { + "doi": "10.1038/s41556-021-00642-9", + "comment": "M. musculus orthologue: Aida, Ucp1" + }, + "passages": [ + { + "infons": { + "journal": "Nat Cell Biol. 2021 Mar;23(3):268-277. doi: 10.1038/s41556-021-00642-9. Epub 2021 ", + "year": "2021", + "type": "title", + "authors": "Shi M, Huang XY, Ren XY, Wei XY, Ma Y, Lin ZZ, Liu DT, Song L, Zhao TJ, Li G, Yao L, Zhu M, Zhang C, Xie C, Wu Y, Wu HM, Fan LP, Ou J, Zhan YH, Lin SY, Lin SC" }, - { - "infons": { - "type": "abstract" - }, - "offset": 82, - "text": "The sympathetic nervous system-catecholamine-uncoupling protein 1 (UCP1) axis plays an essential role in non-shivering adaptive thermogenesis. However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA). Phosphorylated AIDA translocates to the intermembrane space, where it binds to and activates the uncoupling activity of UCP1 by promoting cysteine oxidation of UCP1. Adipocyte-specific depletion of AIDA abrogates UCP1-dependent thermogenesis, resulting in hypothermia during acute cold exposure. Re-expression of S161A-AIDA, unlike wild-type AIDA, fails to restore the acute cold response in Aida-knockout mice. The PKA-AIDA-UCP1 axis is highly conserved in mammals, including hibernators. Denervation of the sympathetic postganglionic fibres abolishes cold-induced AIDA-dependent thermogenesis. These findings uncover a direct mechanistic link between sympathetic input and UCP1-mediated adaptive thermogenesis.", - "sentences": [], - "annotations": [ - { - "id": "25", - "infons": { - "identifier": "MESH:D002395", - "type": "Chemical", - "valid": true, - "normalized": [ - "D002395" - ], - "database": "ncbi_mesh", - "normalized_id": "D002395", - "biotype": "chemical", - "name": "Catecholamines", - "accession": "@CHEMICAL_Catecholamines" - }, - "text": "catecholamine", - "locations": [ - { - "offset": 113, - "length": 13 - } - ] - }, - { - "id": "26", - "infons": { - "identifier": "22227", - "type": "Gene", - "ncbi_homologene": "22524", - "valid": true, - "normalized": [ - 22227 - ], - "database": "ncbi_gene", - "normalized_id": 22227, - "biotype": "gene", - "name": "Ucp1", - "accession": "@GENE_UCP1" - }, - "text": "UCP1", - "locations": [ - { - "offset": 149, - "length": 4 - } - ] - }, - { - "id": "27", - "infons": { - "identifier": "MESH:D002395", - "type": "Chemical", - "valid": true, - 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However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA). Phosphorylated AIDA translocates to the intermembrane space, where it binds to and activates the uncoupling activity of UCP1 by promoting cysteine oxidation of UCP1. Adipocyte-specific depletion of AIDA abrogates UCP1-dependent thermogenesis, resulting in hypothermia during acute cold exposure. Re-expression of S161A-AIDA, unlike wild-type AIDA, fails to restore the acute cold response in Aida-knockout mice. The PKA-AIDA-UCP1 axis is highly conserved in mammals, including hibernators. Denervation of the sympathetic postganglionic fibres abolishes cold-induced AIDA-dependent thermogenesis. These findings uncover a direct mechanistic link between sympathetic input and UCP1-mediated adaptive thermogenesis.", + "sentences": [], + "annotations": [ + { + "id": "25", + "infons": { + "identifier": "MESH:D002395", + "type": "Chemical", + "valid": true, + "normalized": ["D002395"], + "database": "ncbi_mesh", + "normalized_id": "D002395", + "biotype": "chemical", + "name": "Catecholamines", + "accession": "@CHEMICAL_Catecholamines" }, - { - "id": "37", - "infons": { - "identifier": "tmVar:p|SUB|S|161|A;HGVS:p.S161A;VariantGroup:0;OriginalGene:108909;CorrespondingGene:64853;CorrespondingSpecies:10090", - "type": "Variant", - "valid": true, - "subtype": "ProteinMutation", - "database": "litvar", - "hgvs": "p.S161A", - "original_genes_ids": [ - 108909 - ], - "original_gene_id": 108909, - "gene_ids": [ - 64853 - ], - "gene_id": 64853, - "species_ids": [ - 10090 - ], - "species_id": 10090, - "rsids": [], - "normalized": [ - "#64853#p.S161A", - "#64853#" - ], - "normalized_id": "#64853#p.S161A", - 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"_id": "34546791|None", - "id": "10.1126/scisignal.abf3535", - "infons": { - "doi": "10.1126/scisignal.abf3535", - "comment": "Synonym + ortholog: p50, p65; red-herring: NF-kappaB; title organism; IL-1beta totally buried" - }, - "passages": [ - { - "infons": { - "journal": "Sci Signal. 2021 Sep 21;14(701):eabf3535. doi: 10.1126/scisignal.abf3535. Epub ", - "year": "2021", - "article-id_pmc": "PMC8734558", - "type": "title", - "authors": "Catheline SE, Bell RD, Oluoch LS, James MN, Escalera-Rivera K, Maynard RD, Chang ME, Dean C, Botto E, Ketz JP, Boyce BF, Zuscik MJ, Jonason JH" - }, - "offset": 0, - "text": "IKKbeta-NF-kappaB signaling in adult chondrocytes promotes the onset of age-related osteoarthritis in mice.", - "sentences": [], - "annotations": [ - { - "id": "4", - "infons": { - "identifier": "16150", - "type": "Gene", - "ncbi_homologene": "7782", - "valid": true, - "normalized": [ - 16150 - ], - "database": "ncbi_gene", - "normalized_id": 16150, - "biotype": "gene", - "name": "Ikbkb", - "accession": "@GENE_IKBKB" - }, - "text": "IKKbeta", - "locations": [ - { - "offset": 0, - "length": 7 - } - ] - }, - { - "id": "5", - "infons": { - "identifier": "18033", - "type": "Gene", - "ncbi_homologene": "2971", - "valid": true, - "normalized": [ - 18033 - ], - "database": "ncbi_gene", - "normalized_id": 18033, - "biotype": "gene", - "name": "Nfkb1", - "accession": "@GENE_NFKB1" - }, - "text": "NF-kappaB", - "locations": [ - { - "offset": 8, - "length": 9 - } - ] - }, - { - "id": "6", - "infons": { - "identifier": "MESH:D010003", - "type": "Disease", - "valid": true, - "normalized": [ - "D010003" - ], - "database": "ncbi_mesh", - "normalized_id": "D010003", - "biotype": "disease", - "name": "Osteoarthritis", - "accession": "@DISEASE_Osteoarthritis" - }, - "text": "osteoarthritis", - "locations": [ - { - "offset": 84, - "length": 14 - } - ] - }, - { - "id": "7", - "infons": { - "identifier": "10090", - "type": "Species", - "valid": true, - "normalized": [ - 10090 - ], - "database": "ncbi_taxonomy", - "normalized_id": 10090, - "biotype": "species", - "name": "10090", - "accession": null - }, - "text": "mice", - "locations": [ - { - "offset": 102, - "length": 4 - } - ] - } - ], - "relations": [] + "_id": "34546791|None", + "id": "10.1126/scisignal.abf3535", + "infons": { + "doi": "10.1126/scisignal.abf3535", + "comment": "Synonym + ortholog: p50, p65; red-herring: NF-kappaB; title organism; IL-1beta totally buried" + }, + "passages": [ + { + "infons": { + "journal": "Sci Signal. 2021 Sep 21;14(701):eabf3535. doi: 10.1126/scisignal.abf3535. Epub ", + "year": "2021", + "article-id_pmc": "PMC8734558", + "type": "title", + "authors": "Catheline SE, Bell RD, Oluoch LS, James MN, Escalera-Rivera K, Maynard RD, Chang ME, Dean C, Botto E, Ketz JP, Boyce BF, Zuscik MJ, Jonason JH" }, - { - "infons": { - "type": "abstract" - }, - "offset": 108, - "text": "Canonical nuclear factor kappaB (NF-kappaB) signaling mediated by homo- and heterodimers of the NF-kappaB subunits p65 (RELA) and p50 (NFKB1) is associated with age-related pathologies and with disease progression in posttraumatic models of osteoarthritis (OA). Here, we established that NF-kappaB signaling in articular chondrocytes increased with age, concomitant with the onset of spontaneous OA in wild-type mice. Chondrocyte-specific expression of a constitutively active form of inhibitor of kappaB kinase beta (IKKbeta) in young adult mice accelerated the onset of the OA-like phenotype observed in aging wild-type mice, including degenerative changes in the articular cartilage, synovium, and menisci. Both in vitro and in vivo, chondrocytes expressing activated IKKbeta had a proinflammatory secretory phenotype characterized by markers typically associated with the senescence-associated secretory phenotype (SASP). Expression of these factors was differentially regulated by p65, which contains a transactivation domain, and p50, which does not. Whereas the loss of p65 blocked the induction of genes encoding SASP factors in chondrogenic cells treated with interleukin-1beta (IL-1beta) in vitro, the loss of p50 enhanced the IL-1beta-induced expression of some SASP factors. The loss of p50 further exacerbated cartilage degeneration in mice with chondrocyte-specific IKKbeta activation. Overall, our data reveal that IKKbeta-mediated activation of p65 can promote OA onset and that p50 may limit cartilage degeneration in settings of joint inflammation including advanced age.", - "sentences": [], - "annotations": [ - { - "id": "45", - "infons": { - "identifier": "18033", - "type": "Gene", - "ncbi_homologene": "2971", - "valid": true, - "normalized": [ - 18033 - ], - "database": "ncbi_gene", - "normalized_id": 18033, - "biotype": "gene", - "name": "Nfkb1", - "accession": "@GENE_NFKB1" - }, - "text": "NF-kappaB", - "locations": [ - { - "offset": 141, - "length": 9 - } - ] - }, - { - "id": "46", - "infons": { - "identifier": "18033", - "type": "Gene", - "ncbi_homologene": "2971", - "valid": true, - "normalized": [ - 18033 - ], - "database": "ncbi_gene", - "normalized_id": 18033, - "biotype": "gene", - "name": "Nfkb1", - "accession": "@GENE_NFKB1" - }, - "text": "NF-kappaB", - "locations": [ - { - "offset": 204, - "length": 9 - } - ] - }, - { - "id": "47", - "infons": { - "identifier": "19697", - 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"locations": [ - { - "offset": 1457, - "length": 4 - } - ] + "text": "mice", + "locations": [ + { + "offset": 102, + "length": 4 + } + ] + } + ], + "relations": [] + }, + { + "infons": { + "type": "abstract" + }, + "offset": 108, + "text": "Canonical nuclear factor kappaB (NF-kappaB) signaling mediated by homo- and heterodimers of the NF-kappaB subunits p65 (RELA) and p50 (NFKB1) is associated with age-related pathologies and with disease progression in posttraumatic models of osteoarthritis (OA). Here, we established that NF-kappaB signaling in articular chondrocytes increased with age, concomitant with the onset of spontaneous OA in wild-type mice. Chondrocyte-specific expression of a constitutively active form of inhibitor of kappaB kinase beta (IKKbeta) in young adult mice accelerated the onset of the OA-like phenotype observed in aging wild-type mice, including degenerative changes in the articular cartilage, synovium, and menisci. Both in vitro and in vivo, chondrocytes expressing activated IKKbeta had a proinflammatory secretory phenotype characterized by markers typically associated with the senescence-associated secretory phenotype (SASP). Expression of these factors was differentially regulated by p65, which contains a transactivation domain, and p50, which does not. Whereas the loss of p65 blocked the induction of genes encoding SASP factors in chondrogenic cells treated with interleukin-1beta (IL-1beta) in vitro, the loss of p50 enhanced the IL-1beta-induced expression of some SASP factors. The loss of p50 further exacerbated cartilage degeneration in mice with chondrocyte-specific IKKbeta activation. Overall, our data reveal that IKKbeta-mediated activation of p65 can promote OA onset and that p50 may limit cartilage degeneration in settings of joint inflammation including advanced age.", + "sentences": [], + "annotations": [ + { + "id": "45", + "infons": { + "identifier": "18033", + "type": "Gene", + "ncbi_homologene": "2971", + "valid": true, + "normalized": [18033], + "database": "ncbi_gene", + "normalized_id": 18033, + "biotype": "gene", + "name": "Nfkb1", + "accession": "@GENE_NFKB1" }, - { - "id": "75", - "infons": { - "identifier": "16150", - "type": "Gene", - "ncbi_homologene": "7782", - "valid": true, - "normalized": [ - 16150 - ], - "database": "ncbi_gene", - "normalized_id": 16150, - "biotype": "gene", - "name": "Ikbkb", - "accession": "@GENE_IKBKB" - }, - "text": "IKKbeta", - "locations": [ - { - "offset": 1488, - "length": 7 - } - ] + "text": "NF-kappaB", + "locations": [ + { + "offset": 141, + "length": 9 + } + ] + }, + { + "id": "46", + "infons": { + "identifier": "18033", + "type": "Gene", + "ncbi_homologene": "2971", + "valid": true, + "normalized": [18033], + "database": "ncbi_gene", + "normalized_id": 18033, + "biotype": "gene", + "name": "Nfkb1", + "accession": "@GENE_NFKB1" }, - 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"_id": "37317646|None", - "id": "10.15252/embj.2023113616", - "infons": { + "_id": "37317646|None", + "id": "10.15252/embj.2023113616", + "infons": { "doi": "10.15252/embj.2023113616", "comment": "Human, fly and worm (multiple, erroneous IDs) where human is not priority and others are equal" }, - "passages": [ - { - "infons": { - "journal": "EMBO J;2023Jun15 113616. doi:10.15252/embj.2023113616", - "year": "2023", - "article-id_pmc": "PMC10425847", - "type": "title", - "authors": "Dobbelaere J, Su TY, Erdi B, Schleiffer A, Dammermann A, " - }, - "offset": 0, - "text": "A phylogenetic profiling approach identifies novel ciliogenesis genes in Drosophila and C. elegans.", - "sentences": [], - "annotations": [ - { - "id": "2", - "infons": { - "identifier": "7227", - "type": "Species", - "valid": true, - "normalized": [ - 7227 - ], - "database": "ncbi_taxonomy", - "normalized_id": 7227, - "biotype": "species", - "name": "7227", - "accession": null - }, - "text": "Drosophila", - "locations": [ - { - "offset": 73, - "length": 10 - } - ] - }, - { - "id": "3", - "infons": { - "identifier": "6239;252961;314391;316080", - "type": "Species", - "valid": true, - "normalized": [ - 6239 - ], - "database": "ncbi_taxonomy", - "normalized_id": 6239, - "biotype": "species", - "name": "6239", - "accession": null - }, - "text": "C. elegans", - "locations": [ - { - "offset": 88, - "length": 10 - } - ] - } - ], - "relations": [] - }, - { - "infons": { - "type": "abstract" - }, - "offset": 100, - "text": "Cilia are cellular projections that perform sensory and motile functions in eukaryotic cells. A defining feature of cilia is that they are evolutionarily ancient, yet not universally conserved. In this study, we have used the resulting presence and absence pattern in the genomes of diverse eukaryotes to identify a set of 386 human genes associated with cilium assembly or motility. Comprehensive tissue-specific RNAi in Drosophila and mutant analysis in C. elegans revealed signature ciliary defects for 70-80% of novel genes, a percentage similar to that for known genes within the cluster. Further characterization identified different phenotypic classes, including a set of genes related to the cartwheel component Bld10/CEP135 and two highly conserved regulators of cilium biogenesis. We propose this dataset defines the core set of genes required for cilium assembly and motility across eukaryotes and presents a valuable resource for future studies of cilium biology and associated disorders.", - "sentences": [], - "annotations": [ - { - "id": "10", - "infons": { - "identifier": "9606", - "type": "Species", - "valid": true, - "normalized": [ - 9606 - ], - "database": "ncbi_taxonomy", - "normalized_id": 9606, - "biotype": "species", - "name": "9606", - "accession": null - }, - "text": "human", - "locations": [ - { - "offset": 427, - "length": 5 - } - ] - }, - { - "id": "11", - "infons": { - "identifier": "7227", - "type": "Species", - "valid": true, - "normalized": [ - 7227 - ], - "database": "ncbi_taxonomy", - "normalized_id": 7227, - "biotype": "species", - "name": "7227", - "accession": null - }, - "text": "Drosophila", - "locations": [ - { - "offset": 522, - "length": 10 - } - ] - }, - { - "id": "12", - "infons": { - "identifier": "6239;252961;314391;316080", - "type": "Species", - "valid": true, - "normalized": [ - 6239 - ], - "database": "ncbi_taxonomy", - "normalized_id": 6239, - "biotype": "species", - "name": "6239", - "accession": null - }, - "text": "C. elegans", - "locations": [ - { - "offset": 556, - "length": 10 - } - ] - }, - { - "id": "13", - "infons": { - "identifier": "MESH:D002925", - "type": "Disease", - "valid": true, - "normalized": [ - "D002925" - ], - "database": "ncbi_mesh", - "normalized_id": "D002925", - "biotype": "disease", - "name": "Ciliary Motility Disorders", - "accession": "@DISEASE_Ciliary_Motility_Disorders" - }, - "text": "ciliary defects", - "locations": [ - { - "offset": 586, - "length": 15 - } - ] - }, - { - "id": "14", - "infons": { - "identifier": "39647", - "type": "Gene", - "ncbi_homologene": "45709", - "valid": true, - "normalized": [ - 39647 - ], - "database": "ncbi_gene", - "normalized_id": 39647, - "biotype": "gene", - "name": "Cep135", - "accession": "@GENE_CEP135" - }, - "text": "Bld10", - "locations": [ - { - "offset": 820, - "length": 5 - } - ] - }, - { - "id": "15", - "infons": { - "identifier": "9662", - "type": "Gene", - "ncbi_homologene": "45709", - "valid": true, - "normalized": [ - 9662 - ], - "database": "ncbi_gene", - "normalized_id": 9662, - "biotype": "gene", - "name": "CEP135", - "accession": "@GENE_CEP135" - }, - "text": "CEP135", - "locations": [ - { - "offset": 826, - "length": 6 - } - ] - } - ], - "relations": [] - } - ], - "relations": [], - "pmid": 37317646, - "pmcid": null, - "meta": {}, - "date": "2023-06-15T00:00:00Z", - "journal": "EMBO J", - "authors": [ - "Dobbelaere J", - "Su TY", - "Erdi B", - "Schleiffer A", - "Dammermann A" - ], - "relations_display": [] -} \ No newline at end of file + "passages": [ + { + "infons": { + "journal": "EMBO J;2023Jun15 113616. doi:10.15252/embj.2023113616", + "year": "2023", + "article-id_pmc": "PMC10425847", + "type": "title", + "authors": "Dobbelaere J, Su TY, Erdi B, Schleiffer A, Dammermann A, " + }, + "offset": 0, + "text": "A phylogenetic profiling approach identifies novel ciliogenesis genes in Drosophila and C. elegans.", + "sentences": [], + "annotations": [ + { + "id": "2", + "infons": { + "identifier": "7227", + "type": "Species", + "valid": true, + "normalized": [7227], + "database": "ncbi_taxonomy", + "normalized_id": 7227, + "biotype": "species", + "name": "7227", + "accession": null + }, + "text": "Drosophila", + "locations": [ + { + "offset": 73, + "length": 10 + } + ] + }, + { + "id": "3", + "infons": { + "identifier": "6239;252961;314391;316080", + "type": "Species", + "valid": true, + "normalized": [6239], + "database": "ncbi_taxonomy", + "normalized_id": 6239, + "biotype": "species", + "name": "6239", + "accession": null + }, + "text": "C. elegans", + "locations": [ + { + "offset": 88, + "length": 10 + } + ] + } + ], + "relations": [] + }, + { + "infons": { + "type": "abstract" + }, + "offset": 100, + "text": "Cilia are cellular projections that perform sensory and motile functions in eukaryotic cells. A defining feature of cilia is that they are evolutionarily ancient, yet not universally conserved. In this study, we have used the resulting presence and absence pattern in the genomes of diverse eukaryotes to identify a set of 386 human genes associated with cilium assembly or motility. Comprehensive tissue-specific RNAi in Drosophila and mutant analysis in C. elegans revealed signature ciliary defects for 70-80% of novel genes, a percentage similar to that for known genes within the cluster. Further characterization identified different phenotypic classes, including a set of genes related to the cartwheel component Bld10/CEP135 and two highly conserved regulators of cilium biogenesis. We propose this dataset defines the core set of genes required for cilium assembly and motility across eukaryotes and presents a valuable resource for future studies of cilium biology and associated disorders.", + "sentences": [], + "annotations": [ + { + "id": "10", + "infons": { + "identifier": "9606", + "type": "Species", + "valid": true, + "normalized": [9606], + "database": "ncbi_taxonomy", + "normalized_id": 9606, + "biotype": "species", + "name": "9606", + "accession": null + }, + "text": "human", + "locations": [ + { + "offset": 427, + "length": 5 + } + ] + }, + { + "id": "11", + "infons": { + "identifier": "7227", + "type": "Species", + "valid": true, + "normalized": [7227], + "database": "ncbi_taxonomy", + "normalized_id": 7227, + "biotype": "species", + "name": "7227", + "accession": null + }, + "text": "Drosophila", + "locations": [ + { + "offset": 522, + "length": 10 + } + ] + }, + { + "id": "12", + "infons": { + "identifier": "6239;252961;314391;316080", + "type": "Species", + "valid": true, + "normalized": [6239], + "database": "ncbi_taxonomy", + "normalized_id": 6239, + "biotype": "species", + "name": "6239", + "accession": null + }, + "text": "C. elegans", + "locations": [ + { + "offset": 556, + "length": 10 + } + ] + }, + { + "id": "13", + "infons": { + "identifier": "MESH:D002925", + "type": "Disease", + "valid": true, + "normalized": ["D002925"], + "database": "ncbi_mesh", + "normalized_id": "D002925", + "biotype": "disease", + "name": "Ciliary Motility Disorders", + "accession": "@DISEASE_Ciliary_Motility_Disorders" + }, + "text": "ciliary defects", + "locations": [ + { + "offset": 586, + "length": 15 + } + ] + }, + { + "id": "14", + "infons": { + "identifier": "39647", + "type": "Gene", + "ncbi_homologene": "45709", + "valid": true, + "normalized": [39647], + "database": "ncbi_gene", + "normalized_id": 39647, + "biotype": "gene", + "name": "Cep135", + "accession": "@GENE_CEP135" + }, + "text": "Bld10", + "locations": [ + { + "offset": 820, + "length": 5 + } + ] + }, + { + "id": "15", + "infons": { + "identifier": "9662", + "type": "Gene", + "ncbi_homologene": "45709", + "valid": true, + "normalized": [9662], + "database": "ncbi_gene", + "normalized_id": 9662, + "biotype": "gene", + "name": "CEP135", + "accession": "@GENE_CEP135" + }, + "text": "CEP135", + "locations": [ + { + "offset": 826, + "length": 6 + } + ] + } + ], + "relations": [] + } + ], + "relations": [], + "pmid": 37317646, + "pmcid": null, + "meta": {}, + "date": "2023-06-15T00:00:00Z", + "journal": "EMBO J", + "authors": [ + "Dobbelaere J", + "Su TY", + "Erdi B", + "Schleiffer A", + "Dammermann A" + ], + "relations_display": [] +} diff --git a/test/pubtator/pubtator.js b/test/pubtator/pubtator.js index f5114efe..3206f8d1 100644 --- a/test/pubtator/pubtator.js +++ b/test/pubtator/pubtator.js @@ -1,25 +1,128 @@ -import { pubtator_2 } from './10.1016_j.molcel.2019.03.023.json'; -import { pubtator_4 } from './10.1016_j.molcel.2024.01.007.json'; -import { pubtator_5 } from './10.1038_s41556-021-00642-9.json'; -import { pubtator_6 } from './10.1126_scisignal.abf3535.json'; -import { pubtator_7 } from './10.15252_embj.2023113616.json'; +import { expect } from 'chai'; +import _ from 'lodash'; -/** +import { Hint, HINT_TYPE, SECTION } from '../../src/model/hint.js'; +import map from '../../src/server/routes/api/document/hint/pubtator.js'; + +import pubtator_2 from './10.1016_j.molcel.2019.03.023.json'; +import pubtator_5 from './10.1038_s41556-021-00642-9.json'; +import pubtator_6 from './10.1126_scisignal.abf3535.json'; +import pubtator_7 from './10.15252_embj.2023113616.json'; +import pubtator_8 from './pubtator_8.json'; + +/** * bioCDocuments - * + * * This is an array of object documents that have set of fields { _id, infons, passages, relations, pmid, etc. } - * A passage is and array of 2 objects, each object is either of type: { title or abstract }, and has an + * A passage is and array of 2 objects, each object is either of type: { title or abstract }, and has an * annotations array of objects where each object indicates the id and the type of the bioentity (i.e gene, species, etc). -*/ + * + * In the comments below, There is a field at the end of each bioCDocument object called "text" , which is an array devided into 2 arrays, the first array is hints from title, and the second array is hints from abstract. + */ const bioCDocuments = [ - //0..1 - pubtator_2, // pmid: 31003867 | 0 organism hints in title { } | 1 organism hints in abstract: { 10090 aka (Mus musculus): 1 } | text: [ [] , ["mouse"] ] - //0..0 - pubtator_4, // pmid: 38309274 | 0 organism hints in title { } | 0 organism hints in abstract: { } | text: [ [] , [] ] - //0..1 - pubtator_5, // pmid: 33664495 | 0 organism hints in title { } | 1 organism hints in abstract: { 10090 aka (Mus musculus): 1 } | text: [ [] , ["mice"] ] - //1..* - pubtator_6, // pmid: 34546791 | 1 organism hints in title { 10090 aka (Mus musculus): 1 } | 4 organism hints in abstract: { 10090 aka (Mus musculus): 1 } | text: [ ["mice"] , ["mice" , "mice" , "mice" , "mice"] ] - //*..* - pubtator_7 // pmid: 37317646 | 2 organism hints in title { 7227 aka (Drosophila melanogaster): 1 , 6239 aka (Caeonorhabditis elegans): 1 } | 3 organism hints in abstract: { 9606 aka (Homo sapiens): 1 , 7227 aka (Drosophila melanogaster): 1 , 6239 aka (Caeonorhabditis elegans): 1 } | text: [ [ "Drosophila" , "C. elegans"] , [ "human" , "Drosophila" , "C. elegans" ] ] - ]; \ No newline at end of file + // 0..1 (one organism hint in abstract) + pubtator_2, // pmid: 31003867 | 0 organism hints in title { } | 1 organism hints in abstract: { 10090 aka (Mus musculus): 1 } | text: [ [] , ["mouse"] ] + //0..1 (one organism hint in abstract) + pubtator_5, // pmid: 33664495 | 0 organism hints in title { } | 1 organism hints in abstract: { 10090 aka (Mus musculus): 1 } | text: [ [] , ["mice"] ] + //1..* (one organism hint in title and multiple organism hints in abstract) + pubtator_6, // pmid: 34546791 | 1 organism hints in title { 10090 aka (Mus musculus): 1 } | 4 organism hints in abstract: { 10090 aka (Mus musculus): 4 } | text: [ ["mice"] , ["mice" , "mice" , "mice" , "mice"] ] + //1..* (one organism hint in title and multiple organism hints in abstract) + pubtator_7, // pmid: 37317646 | 1 organism hints in title { 7227 aka (Drosophila melanogaster): 1 } | 2 organism hints in abstract: { 9606 aka (Homo sapiens): 1 , 7227 aka (Drosophila melanogaster): 1 } | text: [ [ "Drosophila" ] , [ "human" , "Drosophila" ] ] + //*..* (multiple organisms in title, and multiple organism hints in abstract) + pubtator_8, // pmid: 24633240 | 2 organism hints in title { 9606 aka (Homo sapiens): 1 , 10090 aka (Mus musculus): 1} | 2 organism hints in title { 9606 aka (Homo sapiens): 12 , 10090 aka (Mus musculus): 7} | text [ [ "human" , "mouse"] , [ "Mice", "human" , "human" , "mouse" , "human" , "mouse" , "human" , "mouse" , "human" , "human" , "mice" , "Human" , "human" , "mice" , "human" , "patients" , "mouse" , "human" , "human" ] ] +]; + +describe('pubtator', function () { + describe('map', function () { + bioCDocuments.forEach((bioCDocument) => { + const { + infons: { doi }, + } = bioCDocument; + + describe(`BioC Document ${doi}`, function () { + let hints; + + before(() => { + hints = map(bioCDocument); + }); + + it('Should map to a non-zero list', function () { + expect(hints).to.have.length.above(0); + }); + + it('Should map to a list of Hints', function () { + hints.forEach((h) => { + expect(h).to.be.an.instanceof(Hint); + }); + }); + + it('Should have valid section', function () { + const isValidSection = (h) => _.includes(SECTION, h.section); + expect(hints.every(isValidSection)).to.be.true; + }); + + it('Should have valid texts field', function () { + const hasTexts = (h) => h.texts instanceof Array; + expect(hints.every(hasTexts)).to.be.true; + }); + + it('Should have unique xref in a given section', function () { + const bySectionXref = ({ xref, section }) => + `${xref.dbPrefix}_${xref.id}_${section}`; + const inTitle = _.filter(hints, ['section', 'title']); + const uniqInTitle = _.uniqBy(inTitle, bySectionXref); + const inAbstract = _.filter(hints, ['section', 'abstract']); + const uniqInAbstract = _.uniqBy(inAbstract, bySectionXref); + expect(inTitle.length).to.equal(uniqInTitle.length); + expect(inAbstract.length).to.equal(uniqInAbstract.length); + }); + + it(`Should be all an ORGANISM hint`, function () { + const isOrganism = (h) => h.type === HINT_TYPE.ORGANISM; + expect(hints.every(isOrganism)).to.be.true; + }); + + it('Should aggregate organism hints correctly', function () { + const aggregateCounts = hints.reduce((acc, hint) => { + const key = `${hint._xref.id}_${hint.section}`; + acc[key] = (acc[key] || 0) + hint._texts.length; + return acc; + }, {}); + + if (pubtator_2 === bioCDocument) { + const expectedCounts = { + '10090_abstract': 1, + }; + expect(aggregateCounts).to.deep.equal(expectedCounts); + } else if (pubtator_5 === bioCDocument) { + const expectedCounts = { + '10090_abstract': 1, + }; + expect(aggregateCounts).to.deep.equal(expectedCounts); + } else if (pubtator_6 === bioCDocument) { + const expectedCounts = { + '10090_title': 1, + '10090_abstract': 4, + }; + expect(aggregateCounts).to.deep.equal(expectedCounts); + } else if (pubtator_7 === bioCDocument) { + const expectedCounts = { + '7227_title': 1, + '9606_abstract': 1, + '7227_abstract': 1, + }; + expect(aggregateCounts).to.deep.equal(expectedCounts); + } else if (pubtator_8 === bioCDocument) { + const expectedCounts = { + '9606_title': 1, + '10090_title': 1, + '9606_abstract': 12, + '10090_abstract': 7, + }; + expect(aggregateCounts).to.deep.equal(expectedCounts); + } + }); + }); // BioC Document + }); // forEach + }); // map +}); // pubtator diff --git a/test/pubtator/pubtator_8.json b/test/pubtator/pubtator_8.json new file mode 100644 index 00000000..3499bb2f --- /dev/null +++ b/test/pubtator/pubtator_8.json @@ -0,0 +1,578 @@ +{ + "_id": "24633240|None", + "id": "24633240", + "infons": { + "doi": "24633240 (needs finishing)...", + "comment": "Human, mouse (needs finishing)..." + }, + "passages": [ + { + "infons": { + "journal": "Nat Biotechnol. 2014 Apr;32(4):364-72. doi: 10.1038/nbt.2858. Epub 2014 Mar 16.", + "year": "2014", + "article-id_pmc": "PMC4017589", + "type": "title", + "authors": "Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV, Teichmann LL, Saito Y, Marches F, Halene S, Palucka AK, Manz MG, Flavell RA" + }, + "offset": 0, + "text": "Development and function of human innate immune cells in a humanized mouse model.", + "sentences": [], + "annotations": [ + { + "id": "2", + "infons": { + "identifier": "9606", + "type": "Species", + "valid": true, + "normalized": [9606], + "database": "ncbi_taxonomy", + "normalized_id": 9606, + "biotype": "species", + "name": "9606", + "accession": null + }, + "text": "human", + "locations": [ + { + "offset": 28, + "length": 5 + } + ] + }, + { + "id": "3", + "infons": { + "identifier": "10090", + "type": "Species", + "valid": true, + "normalized": [10090], + "database": "ncbi_taxonomy", + "normalized_id": 10090, + "biotype": "species", + "name": "10090", + "accession": null + }, + "text": "mouse", + "locations": [ + { + "offset": 69, + "length": 5 + } + ] + } + ], + "relations": [] + }, + { + "infons": { + "type": "abstract" + }, + "offset": 82, + "text": "Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology. ", + "sentences": [], + "annotations": [ + { + "id": "27", + "infons": { + "identifier": "10090", + "type": "Species", + "valid": true, + "normalized": [10090], + "database": "ncbi_taxonomy", + "normalized_id": 10090, + "biotype": "species", + "name": "10090", + "accession": null + }, + "text": "Mice", + "locations": [ + { + "offset": 82, + "length": 4 + } + ] + }, + { + "id": "28", + "infons": { + "identifier": "9606", + "type": "Species", + "valid": true, + "normalized": [9606], + "database": "ncbi_taxonomy", + "normalized_id": 9606, + "biotype": "species", + "name": "9606", + "accession": null + }, + "text": "human", + "locations": [ + { + "offset": 104, + "length": 5 + } + ] + }, + { + "id": "29", + "infons": { + "identifier": "9606", + "type": "Species", + "valid": true, + "normalized": [9606], + "database": "ncbi_taxonomy", + "normalized_id": 9606, + "biotype": "species", + "name": "9606", + "accession": null + }, + "text": "human", + "locations": [ + { + "offset": 167, + "length": 5 + } + ] + }, + { + "id": "30", + "infons": { + "identifier": "10090", + "type": "Species", + "valid": true, + "normalized": [10090], + "database": "ncbi_taxonomy", + "normalized_id": 10090, + "biotype": "species", + "name": "10090", + "accession": null + }, + "text": "mouse", + "locations": [ + { + "offset": 244, + "length": 5 + } + ] + }, + { + "id": "31", + "infons": { + "identifier": "9606", + "type": "Species", + "valid": true, + "normalized": [9606], + "database": "ncbi_taxonomy", + "normalized_id": 9606, + "biotype": "species", + "name": "9606", + "accession": null + }, + "text": "human", + "locations": [ + { + "offset": 287, + "length": 5 + } + ] + }, + { + "id": "32", + "infons": { + "identifier": "10090", + "type": "Species", + "valid": true, + "normalized": [10090], + "database": "ncbi_taxonomy", + "normalized_id": 10090, + "biotype": "species", + "name": "10090", + "accession": null + }, + "text": "mouse", + "locations": [ + { + "offset": 390, + "length": 5 + } + ] + }, + { + "id": "33", + "infons": { + "identifier": "9606", + "type": "Species", + "valid": true, + "normalized": [9606], + "database": "ncbi_taxonomy", + "normalized_id": 9606, + "biotype": "species", + "name": "9606", + "accession": null + }, + "text": "human", + "locations": [ + { + "offset": 438, + "length": 5 + } + ] + }, + { + "id": "34", + "infons": { + "identifier": "10090", + "type": "Species", + "valid": true, + "normalized": [10090], + "database": "ncbi_taxonomy", + "normalized_id": 10090, + "biotype": "species", + "name": "10090", + "accession": null + }, + "text": "mouse", + "locations": [ + { + "offset": 565, + "length": 5 + } + ] + }, + { + "id": "35", + "infons": { + "identifier": "9606", + "type": "Species", + "valid": true, + "normalized": [9606], + "database": "ncbi_taxonomy", + "normalized_id": 9606, + "biotype": "species", + "name": "9606", + "accession": null + }, + "text": "human", + "locations": [ + { + "offset": 581, + "length": 5 + } + ] + }, + { + "id": 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