Difference between revisions of "Bioscape Scoring Techniques"

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{{:Bioscape Status}}
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This document provides examples of some of the adopted and proposed techniques for scoring source and result data in order to more accurately identify bioentities in the literature.
 
This document provides examples of some of the adopted and proposed techniques for scoring source and result data in order to more accurately identify bioentities in the literature.
  
Line 202: Line 204:
  
 
* suggestion not confirmed by explanation
 
* suggestion not confirmed by explanation
 
=== PubMed #7512734 ===
 
 
"Here another '''guanine nucleotide-releasing protein (GNRP)''', C3G, has been
 
identified as a CRK SH3-binding protein."
 
 
{| cellspacing="0" cellpadding="5" border="0" style="margin: 2em"
 
| Here another
 
| style="border: 1px solid #000000" | guanine nucleotide-releasing protein
 
| (
 
| style="border: 1px solid #000000" | GNRP
 
| )
 
|-
 
|
 
| suggestion/explanation
 
|
 
| suggestion
 
|
 
|-
 
|
 
| style="border: 1px solid #000000" | RCC1 (#1104)
 
|
 
| style="border: 1px solid #000000" | RASGRF1 (#5923)
 
|
 
|}
 
 
* suggestions contradict each other
 
* the suggestion for the acronym should be disregarded
 
  
 
=== PubMed #9569054 ===
 
=== PubMed #9569054 ===
Line 284: Line 258:
 
* inappropriate suggestion should have been redefined
 
* inappropriate suggestion should have been redefined
 
* later mentions of "Nmi" are thus also inappropriate
 
* later mentions of "Nmi" are thus also inappropriate
 +
 +
=== PubMed #9092545 ===
 +
 +
Sometimes, recognition of acronym explanations can be quite involved:
 +
 +
"The 130-kDa cytosolic enzyme was purified to homogeneity and shown by tryptic peptide and reverse transcriptase- polymerase chain reaction (RT-PCR)-amplified rat cDNA sequence analyses to be structurally related to the 116-kDa '''rat hepatic PAK-1/protein kinase N (PKN)''' and, even more closely (95% sequence identity) to the 130-kDa human PKC-related kinase, PRK2."
 +
 +
{| cellspacing="0" cellpadding="5" border="0" style="margin: 2em"
 +
| rat hepatic
 +
| style="border: 1px solid #000000" | PAK-1
 +
| /
 +
| style="border: 1px solid #000000" | protein kinase N
 +
| (
 +
| style="border: 1px solid #000000" | PKN
 +
| )
 +
|-
 +
|
 +
| suggestions
 +
|
 +
| acronym explanation
 +
|
 +
| acronym/suggestion
 +
|-
 +
|
 +
| style="border: 1px solid #000000" | PAK1 (#5058)<br>PKN1 (#5585)
 +
|
 +
|
 +
|
 +
| style="border: 1px solid #000000" | PKN1 (#5585)
 +
|}
 +
 +
* the detected acronym explanation does not support the acronym suggestion
 +
* the adjacent text "PAK-1" does support the acronym suggestion
  
 
=== PubMed #10878382 ===
 
=== PubMed #10878382 ===
Line 318: Line 325:
  
 
* PPBP (#5473) is chosen in preference to NAP1L4 (#4676) and NAPSB (#256236)
 
* PPBP (#5473) is chosen in preference to NAP1L4 (#4676) and NAPSB (#256236)
 +
 +
=== PubMed #7512734 ===
 +
 +
Method: <tt>disambiguated_by_acronym</tt>
 +
 +
"Here another '''guanine nucleotide-releasing protein (GNRP)''', C3G, has been
 +
identified as a CRK SH3-binding protein."
 +
 +
{| cellspacing="0" cellpadding="5" border="0" style="margin: 2em"
 +
| Here another
 +
| style="border: 1px solid #000000" | guanine nucleotide-releasing protein
 +
| (
 +
| style="border: 1px solid #000000" | GNRP
 +
| )
 +
|-
 +
|
 +
| suggestion/explanation
 +
|
 +
| suggestion
 +
|
 +
|-
 +
|
 +
| style="border: 1px solid #000000" | RCC1 (#1104)
 +
|
 +
| style="border: 1px solid #000000" | RASGRF1 (#5923)
 +
|
 +
|}
 +
 +
* suggestions contradict each other
 +
* the suggestion for the acronym should be disregarded
  
 
== Confirmation of Mention Suggestions ==
 
== Confirmation of Mention Suggestions ==
Line 539: Line 576:
  
 
== Chromosome Information Correspondence ==
 
== Chromosome Information Correspondence ==
 +
 +
Method: <tt>confirmed_by_chromosome_mention</tt>
  
 
=== PubMed #10072425 ===
 
=== PubMed #10072425 ===
Line 566: Line 605:
 
* Note that "X chromosome" is also mentioned in the sentence.
 
* Note that "X chromosome" is also mentioned in the sentence.
  
 +
== Using Parentheses as Result Regions ==
 +
 +
Text enclosed within brackets could be regarded as a region corresponding to a particular result, and existing techniques could then be applied to such broader regions.
 +
 +
=== PubMed #2365818 ===
 +
 +
"Nucleotide sequence analysis revealed that the isolated '''cDNA clone (lambda hBE1 beta-1)''' contained a 5'-untranslated sequence of four nucleotides, the translated sequence of 1,176 nucleotides and the 3'-untranslated sequence of 169 nucleotides."
 +
 +
{| cellspacing="0" cellpadding="5" border="0" style="margin: 2em"
 +
| style="border: 1px solid #000000" | cDNA clone
 +
| (
 +
| lambda
 +
| style="border: 1px solid #000000" | hBE1
 +
| beta-1)
 +
|-
 +
| type-specific term
 +
|
 +
|
 +
| suggestion
 +
|
 +
|-
 +
| style="border: 1px solid #000000" | reference to cDNA
 +
|
 +
|
 +
| style="border: 1px solid #000000" | HBE1 (#3046)
 +
|
 +
|}
 +
 +
* the type-specific term preceding the parentheses could force a specific interpretation of the contents of the parentheses
 +
* a simpler approach for gene identification could involve incorporating "lambda" and "beta" as keywords which disqualify a gene mention if they appear next to a mention
 +
 +
== Applying Disqualifying Keywords to Mentions ==
 +
 +
=== PubMed #1731328 ===
 +
 +
"We now present cloning of a cDNA coding for CHED (cholinesterase-related cell division controller), '''a human homolog of the Schizosaccharomyces pombe cell division cycle 2 (cdc2)-like kinases''', universal controllers of the mitotic cell cycle."
 +
 +
{| cellspacing="0" cellpadding="5" border="0" style="margin: 2em"
 +
| a human homolog of the Schizosaccharomyces pombe
 +
| style="border: 1px solid #000000" | cell division cycle 2
 +
| (
 +
| style="border: 1px solid #000000" | cdc2
 +
| )-
 +
| style="border: 1px solid #000000" | like
 +
|
 +
| style="border: 1px solid #000000" | kinases
 +
|-
 +
|
 +
| suggestion
 +
|
 +
| suggestion
 +
|
 +
| disqualifier keyword
 +
|
 +
| disqualifier keyword
 +
|-
 +
|
 +
| style="border: 1px solid #000000" | CDC2 (#983)
 +
|
 +
| style="border: 1px solid #000000" | CDC2 (#983)<br>POLD1 (#5424)
 +
|
 +
| style="border: 1px solid #000000" | indicates something other than the suggested bioentity
 +
|
 +
| style="border: 1px solid #000000" | reference to kinases
 +
|}
 +
 +
* the disqualification applying to the bracketed term should also apply to the equivalent preceding term
 +
* the reference to "the human homolog" could be used to disambiguate between species-specific bioentities
 +
 +
== Assuming the Presence of Gene Symbols ==
 +
 +
One technique amongst many that assert different claims about the kinds of names used for genes by authors is that which claims that where a gene symbol is used, it is more likely to refer to the actual gene being discussed than other names which are not symbolic. However, this is a highly speculative method, as can be seen in the following examples.
 +
 +
=== PubMed #8248256 ===
 +
 +
"Cloning of '''Nrf1, an NF-E2-related transcription factor''', by genetic selection in yeast."
 +
 +
{| cellspacing="0" cellpadding="5" border="0" style="margin: 2em"
 +
| style="border: 1px solid #000000" | Nrf1
 +
| , an NF-E2-related transcription factor
 +
|-
 +
| suggestions
 +
|
 +
|-
 +
| style="border: 1px solid #000000" | NRF1 (#4899) ''symbol''<br>NFE2L1 (#4779) ''not symbol''
 +
|
 +
|}
 +
 +
* although NRF1 is the symbol for gene #4899, this alone does not make it the correct suggestion
 +
* in fact, NFE2L1 is the correct suggestion
 +
 +
=== PubMed #9931490 ===
 +
 +
"'''XCE, a new member of the endothelin-converting enzyme and neutral endopeptidase family''', is preferentially expressed in the CNS."
 +
 +
{| cellspacing="0" cellpadding="5" border="0" style="margin: 2em"
 +
| style="border: 1px solid #000000" | XCE
 +
| , a new member of the
 +
| style="border: 1px solid #000000" | endothelin
 +
| -converting enzyme and neutral
 +
| style="border: 1px solid #000000" | endopeptidase
 +
| family
 +
|-
 +
| suggestions
 +
|
 +
| keyword
 +
|
 +
| keyword
 +
|
 +
|-
 +
| style="border: 1px solid #000000" | XCE (#7497) ''symbol''<br>XIC (#7502)<br>XIST (#7503)<br>ECEL1 (#9427)
 +
|
 +
|
 +
|
 +
| style="border: 1px solid #000000" | referenced in summary for ECEL1 (#9427)
 +
|
 +
|}
 +
 +
* although XCE is the symbol for gene #7497, it is not the correct suggestion
 +
* instead, ECEL (#9427) is the correct suggestion as confirmed by the presence of a gene summary keyword
  
 
[[Category:Bioscape]]
 
[[Category:Bioscape]]

Latest revision as of 13:44, 14 July 2010

NoteNotePlease note that this documentation covers an unreleased product and is for internal use only.

This document provides examples of some of the adopted and proposed techniques for scoring source and result data in order to more accurately identify bioentities in the literature.

Acronym Mentions and Techniques

Once acronym mentions and accompanying definitions or explanations of those acronyms have been found (as described in the "Bioscape Searching Techniques" document), further analysis of such mentions and their application to gene or protein mentions can occur.

PubMed #18370233

"The role of inactivating and activating calcium-sensing receptor (CASR) mutations is discussed"

calcium-sensing receptor ( CASR )
explanation acronym
synonym for CASR (#846) match for CASR (#846)
  • agreement (acronym and explanation support each other)

"with respect to familial hypocalciuric hypercalemia (FHH) and autosomal dominant hypocalemia (ADH)."

familial hypocalciuric hypercalemia ( FHH )
explanation (not detected) acronym
match for CASR (#846)
  • no agreement (if explanation detected speculatively)
  • FHH would not represent CASR despite matching an established gene
  • See also PubMed #18393128: "papillary thyroid carcinomas (PTCs)"

PubMed #19364970

"PATIENTS AND METHODS: In addition to UGT1A1*28, UGT1A1*60, UGT1A1*93, UGT1A7*3, and UGT1A9*22 were genotyped in 250 metastatic colorectal cancer patients, and associations with severe hematologic and nonhematologic toxicity, objective response, time to progression (TTP), and overall survival were evaluated."

time to progression ( TTP )
explanation (not detected) acronym
ZFP36 (#7538)
ADAMTS13 (#11093)
SH3BP4 (#23677)
  • no agreement (if explanation detected speculatively)
  • TTP would not represent ZFP36, ADAMTS13 or SH3BP4

PubMed #18281285

"We have previously shown that ASK1-interacting protein 1 (AIP1) transduces tumor necrosis factor-induced ASK1-JNK signaling."

ASK1-interacting protein 1 ( AIP1 )
explanation acronym
synonym for DAB2IP (#153090) matches for numerous genes including DAB2IP (#153090)
  • agreement for DAB2IP
  • disagreement for other genes associated with AIP1

"Because endoplasmic reticulum (ER) stress activates ASK1-JNK signaling cascade, we investigated the role of AIP1 in ER stress-induced signaling."

endoplasmic reticulum ( ER )
explanation acronym (not detected)
Gene Ontology term
  • no agreement (but the acronym does not require definition)

PubMed #16566752

"In the present study, we subjected CD1 male mice to intraperitoneal injection with TNFalpha (10 ng/mouse) and then examined the expression and localization of DMT1 (divalent metal transporter 1), IREG1 (iron-regulated protein 1) and ferritin in duodenum."

localization of DMT1 ( divalent metal transporter 1 )
suggestion description (not detected)
DMRT1 (#1761)
SLC11A2 (#4891)
CHMP2B (#25978)
summary:
"The SLC11A2 gene encodes a divalent metal transporter (DMT1)"
  • agreement between summary of #4891 and description
  • see also this document in the disambiguation techniques documentation

PubMed #10036216

"Phenobarbital (PB) and many structurally unrelated chemicals induce the protein and mRNA of P450 cytochromes CYP2B1, CYP2B2, CYP3A1, and specific phase II enzymes to a greater extent in Fischer 344 (F344) than in Wistar Furth (WF) female rats."

Phenobarbital ( PB )
explanation suggestion
chemical name SMR3B (#10879)
  • disagreement between suggestion and chemical name

PubMed #2674130

"A new family of ras-related proteins, designated rac (ras-related C3 botulinum toxin substrate) has been identified. rac1 and rac2 cDNA clones were isolated from a differentiated HL-60 library and encode proteins that are 92% homologous and share 58% and 26-30% amino acid homology with human rhos and ras, respectively."

A new family of ras-related proteins, designated rac ( ras-related C3 botulinum toxin substrate )
suggestion explanation (not detected)
AKT1 (#207)
  • suggestion not confirmed by explanation

PubMed #9569054

"The primary end point of the present multicentre, randomized, parallel-group phase II study was to determine the activity of the simplified 2-day EAP schedule in patients with locally advanced or metastatic gastric cancer, and to verify whether the addition of low doses of granulocyte-macrophage colony-stimulating factor (GM-CSF) made it possible to increase dose intensity."

granulocyte-macrophage colony-stimulating factor (GM- CSF )
suggestion/explanation suggestion/acronym
CSF2 (#1437) LAMC2 (#3918)
  • incomplete match for the acronym causes an inappropriate suggestion

PubMed #11916966

"We observed a novel endogenous association of BRCA1 with Nmi (N-Myc-interacting protein) in breast cancer cells."

of BRCA1 with Nmi ( N-Myc-interacting protein )
suggestion suggestion/explanation (not detected)
NMI (#9111)
MYO1C (#4641)
  • inappropriate suggestion should have been redefined
  • later mentions of "Nmi" are thus also inappropriate

PubMed #9092545

Sometimes, recognition of acronym explanations can be quite involved:

"The 130-kDa cytosolic enzyme was purified to homogeneity and shown by tryptic peptide and reverse transcriptase- polymerase chain reaction (RT-PCR)-amplified rat cDNA sequence analyses to be structurally related to the 116-kDa rat hepatic PAK-1/protein kinase N (PKN) and, even more closely (95% sequence identity) to the 130-kDa human PKC-related kinase, PRK2."

rat hepatic PAK-1 / protein kinase N ( PKN )
suggestions acronym explanation acronym/suggestion
PAK1 (#5058)
PKN1 (#5585)
PKN1 (#5585)
  • the detected acronym explanation does not support the acronym suggestion
  • the adjacent text "PAK-1" does support the acronym suggestion

PubMed #10878382

Method: disambiguated_by_acronym

Principle: the transfer of acronym information to other mentions

"The G protein-coupled CXC-chemokine receptor CXCR-2 mediates activation of neutrophil effector functions in response to multiple ligands, including IL-8 and neutrophil-activating peptide 2 (NAP-2)."

neutrophil-activating peptide 2 ( NAP-2 )
explanation acronym
PPBP (#5473) PPBP (#5473)
NAP1L4 (#4676)
NAPSB (#256236)
  • only PPBP (#5473) appears in both lists, thus defining the acronym
  • in other situations where PPBP (#5473) competes with other genes, if such genes were rejected above, they could also be rejected in such cases, too
  • since mentions of "NAP-2" should lead to PPBP (#5473) and any competitors being suggested, PPBP (#5473) should be chosen in such cases

For example:

"Immunoprecipitation and Western blot analyses of surface-expressed receptors covalently linked to IL-8 or NAP-2 as well as in their unloaded state revealed the occurrence of a single CXCR-2 variant with an apparent size of 56 kDa."

  • PPBP (#5473) is chosen in preference to NAP1L4 (#4676) and NAPSB (#256236)

PubMed #7512734

Method: disambiguated_by_acronym

"Here another guanine nucleotide-releasing protein (GNRP), C3G, has been identified as a CRK SH3-binding protein."

Here another guanine nucleotide-releasing protein ( GNRP )
suggestion/explanation suggestion
RCC1 (#1104) RASGRF1 (#5923)
  • suggestions contradict each other
  • the suggestion for the acronym should be disregarded

Confirmation of Mention Suggestions

PubMed #11137999

Method: to be implemented

"Here we report the identification of a new transmembrane serine protease (TMPRSS3; also known as ECHOS1) expressed in many tissues, including fetal cochlea, which is mutated in the families used to describe both the DFNB10 and DFNB8 loci."

( TMPRSS3 ; also known as ECHOS1 )
suggestions suggestion
TMPRSS3 (#64699)
TMPRSS4 (#56649)
TMPRSS3 (#64699)
  • TMPRSS3 (#64699) occurs for both mentions
  • "also known as" could be used as a key to such situations
  • close proximity of mentions (as seen with acronyms) could be sufficient

Note that the above also involves an acronym.

PubMed #7479798

Method: confirmed_by_competing_names

"Cloning and analysis of the full-length cDNA of the human CSE1 homologue, which we name CAS for cellular apoptosis susceptibility gene, reveals a protein coding region with similar length (971 amino acids for CAS, 960 amino acids for CSE1) and 59% overall protein homology to the yeast CSE1 protein."

human CSE1 homologue, which we name CAS
suggestion suggestions
CSE1L (#1434) CSE1L (#1434)
CTNND1 (#1500)
BCAR1 (#9564)
  • CSE1L (#1434) is supported by two different names
  • CTNND1 (#1500) and BCAR1 (#9564) are not supported by any other names
  • the "which we name" text also confirms the equivalence of the two entities

Finding Unambiguous Gene Mentions

In various disambiguation techniques, an unambiguous gene mention may be needed in order to disambiguate between competing gene suggestions. Consequently, a reliable method is needed to find "high quality" suggestions which can be considered as unambiguous gene mentions. Consider the following document excerpt:

PubMed #9788873

"In mouse embryo fibroblasts, TCDD activates expression of multiple genes, including CYP1B1, the predominant cytochrome P450 expressed in these cells."

Mentions Suggestions Methods
unambiguous_at_exact_location not_part_of_other_mentions
CYP1B1 CYP1B1 (#1545) X X
CYP1 CYP1A1 (#1543)
CYP2A (#1546)
CYP27B1 (#1594)
CYP PPIG (#9360) X
  • Here, CYP1B1 (#1545) can be considered at this location as an unambiguous gene mention.

If the above methods taken together are known as an "unambiguous gene mention" method, the fundamental technique can be defined in terms of this method. However, in order to eliminate obvious bad suggestions for genes, it is also necessary to apply other methods in order to identify good suggestions more reliably.

Disambiguating using Unambiguous Mentions

Within the same document, the presence of unambiguous gene mentions can be used to help disambiguate at other mention locations where an unambiguously identified gene may be "competing" with other genes, typically using a name which is ambiguous. For example:

PubMed #10484773

Method: disambiguated_by_unambiguous_gene_mention

"A common genetic variant (V) of the human luteinizing hormone (LH) beta-subunit gene was recently discovered."

of the human luteinizing hormone (LH) beta -subunit gene
suggestion
LHB (#3972)

With this unambiguous mention identified and the presence of the suggested gene confirmed, this knowledge can be applied to other mention locations. For example:

"We have now studied whether additional mutations in the V-LHbeta promoter sequence could contribute to the altered physiology of the LH variant molecules."

in the V-LHbeta promoter sequence
suggestions
LHB (#3972)
PLOD2 (#5352)
LHX2 (#9355)

Since the latter two genes are not unambiguously identified in the document, yet the first gene has been identified (see above), the latter two genes are scored negatively and are regarded as not being referenced.

Note that the confirmed_by_competing_names method also resolves these mentions.

Gene Ontology Correspondence

PubMed #16566752

"In the present study, we subjected CD1 male mice to intraperitoneal injection with TNFalpha (10 ng/mouse) and then examined the expression and localization of DMT1 (divalent metal transporter 1), IREG1 (iron-regulated protein 1) and ferritin in duodenum."

of DMT1 (divalent metal transporter 1), IREG1 (iron-regulated protein 1)
suggestions suggestion
DMRT1 (#1761)
SLC11A2 (#4891)
CHMP2B (#25978)
SLC40A1 (#30061)

Gene Ontology (Function) correspondence could be used:

DMRT1 SLC11A2 CHMP2B IREG1
(#1761) (#4891) (#25978) (#30061)
ferrous iron transmembrane transporter activity X
iron ion binding >2 X X
iron ion transmembrane transporter activity <1 X
metal ion binding X
zinc ion binding X X
  • X: exact match
  • <1: more specific match: ferrous iron transmembrane transporter activity => iron ion transmembrane transporter activity
  • >2: more general match: metal ion binding <= transition metal ion binding <= iron ion binding

Chromosome Information Correspondence

Method: confirmed_by_chromosome_mention

PubMed #10072425

"The t(X;18)(p11.2;q11.2) chromosomal translocation commonly found in synovial sarcomas fuses the SYT gene on chromosome 18 to either of two similar genes, SSX1 or SSX2, on the X chromosome."

the SYT gene on chromosome 18
suggestion information
SS18 (#6760) (chromosome 18)
SYT1 (#6857) (chromosome 12)
chromosome 18
  • SS18 chromosome matches the accompanying information.
  • Note that "X chromosome" is also mentioned in the sentence.

Using Parentheses as Result Regions

Text enclosed within brackets could be regarded as a region corresponding to a particular result, and existing techniques could then be applied to such broader regions.

PubMed #2365818

"Nucleotide sequence analysis revealed that the isolated cDNA clone (lambda hBE1 beta-1) contained a 5'-untranslated sequence of four nucleotides, the translated sequence of 1,176 nucleotides and the 3'-untranslated sequence of 169 nucleotides."

cDNA clone ( lambda hBE1 beta-1)
type-specific term suggestion
reference to cDNA HBE1 (#3046)
  • the type-specific term preceding the parentheses could force a specific interpretation of the contents of the parentheses
  • a simpler approach for gene identification could involve incorporating "lambda" and "beta" as keywords which disqualify a gene mention if they appear next to a mention

Applying Disqualifying Keywords to Mentions

PubMed #1731328

"We now present cloning of a cDNA coding for CHED (cholinesterase-related cell division controller), a human homolog of the Schizosaccharomyces pombe cell division cycle 2 (cdc2)-like kinases, universal controllers of the mitotic cell cycle."

a human homolog of the Schizosaccharomyces pombe cell division cycle 2 ( cdc2 )- like kinases
suggestion suggestion disqualifier keyword disqualifier keyword
CDC2 (#983) CDC2 (#983)
POLD1 (#5424)
indicates something other than the suggested bioentity reference to kinases
  • the disqualification applying to the bracketed term should also apply to the equivalent preceding term
  • the reference to "the human homolog" could be used to disambiguate between species-specific bioentities

Assuming the Presence of Gene Symbols

One technique amongst many that assert different claims about the kinds of names used for genes by authors is that which claims that where a gene symbol is used, it is more likely to refer to the actual gene being discussed than other names which are not symbolic. However, this is a highly speculative method, as can be seen in the following examples.

PubMed #8248256

"Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast."

Nrf1 , an NF-E2-related transcription factor
suggestions
NRF1 (#4899) symbol
NFE2L1 (#4779) not symbol
  • although NRF1 is the symbol for gene #4899, this alone does not make it the correct suggestion
  • in fact, NFE2L1 is the correct suggestion

PubMed #9931490

"XCE, a new member of the endothelin-converting enzyme and neutral endopeptidase family, is preferentially expressed in the CNS."

XCE , a new member of the endothelin -converting enzyme and neutral endopeptidase family
suggestions keyword keyword
XCE (#7497) symbol
XIC (#7502)
XIST (#7503)
ECEL1 (#9427)
referenced in summary for ECEL1 (#9427)
  • although XCE is the symbol for gene #7497, it is not the correct suggestion
  • instead, ECEL (#9427) is the correct suggestion as confirmed by the presence of a gene summary keyword