Analysis of Relevance of Retrieved Documents for Select Queries of TREC Genomics Training Data

Sarah Corley, William Hersh
Oregon Health & Science University

This document presents a summary of the relevance of retrieved documents for 10 queries from the training data of the TREC Genomics Track.  For each topic, all GeneRIFs were analyzed for relevance.  Then the top 20 documents retrieved from the OHSU preliminary experiments were judged for relevance.  All of the relevance judgments were done by Sarah Corley, a physician completing the Information Retrieval course in the OHSU medical informatics program.

After a summary of the data, the topics are presented in order with the topic number, species, gene name, a brief description of gene function, GeneRIF PubMed numbers with relevance determinations, and the top twenty retrieved documents PubMed numbers with relevance determinations. If a document was deemed to be relevant, it is bolded. If it is relevant but refers to another species, it is in bold italics. In a few cases, it was not completely clear if a paper was relevant from the abstract and the full text document was not available. They were sorted into the relevant/non-relevant category depending upon which way Sarah felt they were leaning.

Summary

This table shows an overview of the data.  The first column contains the topic number.  The second and third columns count the number of GeneRIFs and the number deemed relevant for each topic.  As can be seen, 100% of the GeneRIFs were deemed relevant.  The fourth column lists the number of retrieved documents for each topic that were analyzed.  The fifth column contains the number deemed not relevant.  The next three columns list the number of relevant which are GeneRIFs, not GeneRIFs, and relevant but about another species.  The conclusions from this data are very obvious:  GeneRIFs are very accurate indicators of document relevance but significantly incomplete.  The number of incomplete GeneRIFs is highly variable across genes.  The problem of documents which are relevant about the gene but describe another species is also significant.

Topic Number
 GeneRIFs - Total GeneRIFs - Relevant Retrieved - Total Retrieved - Not Relevant Retrieved - Relevant and a GRIF Retrieved - Relevant and not a GRIF Retrieved - Relevant and another species
2 2 2 20 18 1 0 1
3 11 11 20 18 1 1 0
4 8 8 20 0 3 11 6
10 11 11 20 2 0 18 0
11 17 17 20 0 6 14 0
28 7 7 20 0 1 19 0
35 1 1 20 20 0 0 0
36 5 5 20 1 1 9 10
40 8 8 20 5 4 9 2
48 4 4 20 6 4 4 6
Total 74
 74
 200 70 (35%)
 21 (10.5%)
 85 (42.5%)
 25 (12.5%)

Topic 2

Species: Homo sapiens

Gene Name:
"DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 5 (RNA helicase, 68kDa)"

Gene Function:
The gene is located on chromosome 17 in the region of the BRCA1 gene at 17q21. The p68 protein functions in the regulation of cell growth and division. It is important for cell proliferation and organ maturation. This protein is an RNA-helicase with RNA dependent ATPase and RNA unwinding activity. It is highly conserved evolutionarily and exists in almost all types of organisms.

GeneRIFs:
1. 12527917: This is relevant. It discusses the function of the protein p68 expressed by the gene and its interactions with other proteins.
2. 12101238: This is also relevant, as it has to do with the effect of the product protein p68 on other cellular activities.

Relevance of retrieved documents:
1. 12198572 was not relevant. While it mentioned a protein in the same family, it was not the protein expressed by the gene in question (DDX36 instead of DDX5).
2. 11888286 is not relevant. It describes an Escherichia coli protein DbpA of the same family.
3. 12458796 is not relevant. Again it describes a RNA helicase protein but not the pertinent one.
4. 11923195 is not relevant. It is about another RNA helicase, this one in a plant.
5. 12595555 is relevant as long as the search was not to be limited to humans as this is about yeast. It shows the interaction of the p68 protein and p72 and how they function together to regulate mRNA processing. (Yeast)
6. 12527917 is a GeneRIF and is relevant as noted above.
7. 12119114 is not relevant, not even close, perhaps there may be some RNA family characteristics but this is not clear from the abstract.
8. 12110183 is not relevant. It relates to the protein product of a different gene.
9. 12161435 is not relevant. This is talking about a DNA helicase.
10. 12409454 is not relevant. It does not relate at all to the gene or the particular protein.
11. 12183465 is not relevant. It relates to DDX1 not DDX5.
12. 12467973 is not relevant. The focus of this paper is on SMYB1 protein.
13. 12215523 is not relevant. It refers to methylation activity of small nucleolar RNAs and not to any product or function of the relevant gene.
14. 12560482 is not relevant. It relates to different protein products.
15. 12068815 is not relevant. It deals with another gene, the DeaD/CsdA gene
16. 11891046  is not relevant. It deals with genes on chromosomes, 2, 3, 4, and 10
17. 12093383 is not relevant. It is an overview of the T box family and the relevant gene product is a member of the DEAD box protein family.
18. 11867545 is not relevant. It relates to a different protein product.
19. 12477861 is not relevant. It refers to RNA unwinding by a Hep C virus protein.
20. 12402239 is not relevant. It relates to the protein product of a different gene.

Topic 3

Species: Homo sapiens

Gene Name:
ets variant gene 6 (TEL oncogene)
Gene Symbol: ETV6

Gene Function:
The TEL gene (translocation, ETS, leukemia) is located on 12p13. TEL acts as a tumor suppressor and is essential for establishing hematopoiesis in neonatal bone marrow. Rearrangements of this gene are strongly associated with hematopoetic malignancies.

GeneRIFs:
1. 11731410: This is a relevant document that described a malignancy associated with the fusion of ETV6 to the fibroblast growth factor receptor 3 gene.
2. 11861293: This is a relevant document that reports on the protein product of a translocation of the TEL gene.
3. 11861295: This is a relevant document that describes the association of the ETV6 gene with frequent translocations and malignancy.
4. 12080468: This is a relevant document studying whether the protein product of the fusion of ETV6 with another gene is oncogenic.
5. 12091359: This paper is relevant. It examines the presence of a ETV6/AML1 mutation in different cell fractions of patients with childhood ALL to determine the lymphoid progenitor.
6. 12127395: This paper is relevant. It examines two cell lines from a patient with the TEL/AML1 gene fusion at their first and second relapse. The study evaluated the effect of introducing TEL back into the cell line from the second relapse.
7. 12203785: This paper is relevant. It relates a novel gene MDS2 fused with ETV6 found in a patient with Myelodysplastic syndrome.
8. 12210491: This relevant paper examines whether mutational inactivation of ETV6 is associated with prostate cancer.
9. 12393285: This relevant case report documents 2 different mutations in the ETV6 gene in a patient with AML.
10. 12435397: This is a relevant document reporting on the functional regulation of TEL.
11. 12505259: This relevant case report examines the case of a patient with an unusual eosinophilic  CML that was Philadelphia Chromosome negative and had an ETV6-ABL gene fusion.

Relevance of retrieved documents:
1. 12270665: This is not relevant. It has to do with herpes virus 6.
2. 11761710: this is not relevant. It has to do with an ETS gene in a worm.
3. 12200232: This is not relevant, it has to do with ETS 1 not ETV 6
4. 12356738: This is not relevant as it has to do with the alphaIIb gene
5. 12447693: This is not relevant having to do with the Id2 gene
6. 12372283: This is not relevant having to do with the PEA3 gene
7. 11836164: This is not relevant having to do with the Philadelphia chromosome.
8. 11959811: This is not relevant having to do with a different gene and different proteins.
9. 12446726: This is not relevant having to do with another ETS gene product
10. 11991951: This is not relevant having to do with ETS 1
11. 12438253: This is not relevant having to do with a gene on the X chromosome
12. 12036890: This is relevant having to do with the EBV 6 fusion with ABL leading to CML
13. 11926913: This is not relevant having to do with CD44 variant exon 6
14. 12387738: This is not relevant having to do with a different gene and protein product.
15. 12049817: This is not relevant having to do with a different gene
16. 11884602: This is not relevant having to do with a different ETS gene
17. 11986330: This is not relevant having to do with another ETS protein
18. 11861295: Relevant GeneRIF as noted above
19. 12417054: This is not relevant, as it has to do with another gene.
20. 11997188: This is not relevant, having to do with a different gene.

Topic 4

Species: Homo sapiens

Gene Name:
Fibroblast growth factor 7 (keratinocyte growth factor) FGF7

Gene Function:
The KGF7 gene is located on 15q15-q21.1 and produces a growth factor specific for epithelial cells. It has been shown to stimulate the synthesis of surfactant components in the lungs

GeneRIFs:    
1. 11937263: This is a relevant document discussing the effects of KGF on proliferation of hematopoetic cells without differentiation
2. 11943656: This is relevant, it discusses the potential of KGF to repair lung injury.    
3. 11973338: This is relevant discussing the potential effects of KGF    
4. 12008951: This is a relevant document studying the effects of various FGFs on fibroblasts in normal and tumor breast tissue.
5. 12016100: This is a relevant study evaluating the levels of KGF in premature neonates and correlating it with BPD free survival.
6. 12215437: This is a relevant study evaluating substances as potential co-factors to FGF-7 in stimulating cell proliferation.
7. 12243757: This relevant document examines the expression of KGF in young and aging cells.
8. 12438323: This document is relevant mentioning the up regulation of expression of KGF in periodontal disease by a lipopolysaccharide.

Relevance of retrieved documents:
1. 12140734: This is a relevant document detailing an experiment that showed that delivering KGF as a non-viral liposomal cDNA gene complex to rats with wounds improved wound healing. (Rat)
2. 12139706: This is a relevant study documenting the protective effect on mouse tongue epithelium pretreated with KGF prior to exposure to radiation. (Mouse)
3. 12036893: This is a relevant document showing that pretreatment of BMT recipients with keratinocyte growth factor protects mucosal, cutaneous, and pulmonary epithelial cells from cytotoxic therapy-induced damage in experimental murine models. (Mouse)
4. 12384427: This relevant document reports on KGF signaling and its effect on thymic epithelium.
5. 12569015: This relevant document reports that KGF does not stimulate tumor growth and may therefore be used to selectively prevent radiation damage in patients with head & neck cancers.
6. 12139710: This relevant document presents more evidence for the protective effect of KGF in preventing mucositis with either radiation or chemotherapy induced damage.
7. 12060573: This relevant study examined the protective effect of pretreatment with KGF prior to lung injury.
8. 12449173: This relevant document reports on the effects of KGF to preferentially stimulate Clara cells in the lung.
9. 12016100: Relevant GeneRIF as noted above
10. 12354720: This relevant document reports that KGF enhances compensatory lung growth after pneumonectomy in adult rats. (Rat)
11. 12139705: This relevant document reports on the effects of daily injections of KGF on the tongue epithelium of mice. (Mouse)
12. 11937263: Relevant GeneRIF as noted above
13. 11973338: Relevant GeneRIF as noted above
14. 12091365: This relevant document reports on the ability of KGF to avert damage and  maintain thymic function in GVHD
15. 12533693: This relevant document reports on a possible association between cholesteatomas and increased expression of KGF.
16. 12111112: This relevant document evaluated the effects of KGF on rats with breast cancer treated with Methotrexate. (Rat)
17. 12405644: This relevant document showed that KGF administration reversed many of the adverse epithelial changes associated with TPN administration.
18. 12574212: This relevant document reported that KGF stimulated the growth of endometrial carcinoma cells.
19. 12101242: This relevant document reports on the effects of KGF regulated transcription factors in wound healing.
20. 12458339: This relevant document evaluated the signaling pathways for KGF.    

Topic 10

Species: Homo sapiens

Gene Name:
Protein C (inactivator of coagulation factors Va and VIIIa) PROC

Gene Function:
Protein C gene is located on 2q13-q14. It's gene product, protein C is a vitamin K dependent protease which, when activated, selectively destroys coagulation factors V a and VIII a and serves as an anticoagulant. A deficiency of the activated protein leads to a thrombophilic state.

GeneRIFs:
1. 11686318: This relevant document reports on a G-->T transversion at position 1388 of the protein C (PC) gene that was identified in a thrombophilic patient.
2. 11994010: This relevant document studies the role of basic residues on activated protein C by examining normal protein C and that of mutants of the normal protein.
3. 12029084: This relevant document reports on a study the functional significance of two cation sites in the serine protease domain of activated protein C.
4. 12052963: This relevant document discussed the potential role of endothelial cell protease activated receptor 1 in the anticoagulation cascade through the protein C pathway.
5. 12063259: This relevant document discusses  the effects of mutations on the binding of activated protein C(APC) with factor Va.
6. 12067914: This relevant paper reports the association of low levels of Protein C with an increased incidence of venous thromboembolic events.
7. 12091344: This relevant document examines the effects of mutations in factor V in their relationship with activated protein C
8. 12091346: This relevant document reports that activated protein C does not serve as a primary regulator of platelet-dependent thrombin generation.
9. 12193972: This relevant document discusses the Molecular biological basis and diagnosis of hereditary defect of antithrombin III, protein c
10. 12200374: This relevant document presents findings that indicate that activation of protein C by thrombin and inactivation of plasma FVa by APC are not impaired during moderate hyperhomocysteinemia in vivo.
11. 12407115: This relevant document discussed the effects of Smad6s and Smad7 on modulation of protein C activation by endothelial cells.

Relevance of retrieved documents:
1. 11697723: This relevant document reports on a new screening assay to detect defects in the Protein C pathway.
2. 12193972: This relevant document reviews the molecular biological basis of Protein c mutations and resultant disorders.
3. 11897150: This relevant document reports on an additional effect of Activated Protein C on activating Protein C
4. 12139756: This document is relevant. The paper reports that protein C/S ratio seems to be more accurate than the measurement of protein C levels alone to identify carriers of a protein C gene mutation.
5. 11868688: This relevant document reports on the use of activated protein C in severe sepsis in a nursing journal.
6. 12421141: This relevant document reports a consensus guideline for diagnosing Protein C deficiency using lab tests.
7. 12004254: This relevant document reviews the literature about Protein C and sepsis.
8. 12174242: This relevant document is a case report about a patient with Protein C deficiency who had biatrial thrombi.
9. 12134467: This relevant document describes the testing strategies associated with the diagnosis of activated protein C resistance, protein C deficiency, and protein S deficiency.
10. 12204452: This document is not relevant. It is about bivariate linear mixed models using SAS proc MIXED.
11. 12296618: This relevant document reports on the use of activated Protein C in the treatment of sepsis.
12. 11886399: This relevant document reports on the use of plasma exchange as a means of providing Protein C to a patient with meningococcemia.
13. 12105756: This relevant document reports on decreased protein C pathway activation in the airways of patients with asthma possibly contributing to inflammation.
14. 12180620: This relevant document reports on resistance to activated Protein C in a patient with digital artery thrombosis.
15. 12393585: This relevant document reports that oral anticoagulation reduces activated Protein C less than it reduces pro-coagulant factors.
16. 12200374: This relevant document reports on the effect of hyperhomocysteinemia on protein C activation and activity.
17. 12034704: This relevant document describes the crystal structure of the endothelial protein C receptor and a bound phospholipid.
18. 11885409: This relevant document reports on another review article about recombinant human activated protein C in severe sepsis.
19. 12605111: This relevant document reports on a study of the kinetics and magnitude of protein C activation in clinical liver transplantation.
20. 12176392: This non-relevant document reports on a study of a lipopeptide surfactant protein C

Topic 11

Species: Homo sapiens

Gene Name:
Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1). Its alias symbol is TC-25.

Gene Function:
The RAC1 gene has been mapped to 7p22 near PMS2. It is felt to function in the regulation of actin filaments at the plasma membrane, resulting in the production of lamellipodia and ruffles, the generation of reactive oxygen species in phagocytic and nonphagocytic cells, and activation of the family of stress-activated protein kinases.

GeneRIFs:
1. 11685227: This relevant document clarifies the structural elements of the RAC1 gene product that are necessary for it's interactions with the DH/PH domains of the Rac-specific GEF Tiam1    
2. 11822867: This relevant document reports on the effects of negative and active RAC1 mutants on the secretory process of PC12 cells    
3. 11884513: This relevant document shows the importance of Rac1 in the process of endothelial cell vacuole and lumen formation (required for capillary lumen formation) in three-dimensional extracellular matrices.    
4. 11973651: This relevant document reports the effect of activated RAC1 on cell contact inhibition and anchorage dependant growth suggesting a possible role in skeletal muscle tumors.    
5. 12027902: This relevant document reports on the interaction between p21-activated protein kinase and Rac during differentiation of HL-60 human promyelocytic leukemia cell induced by all-trans-retinoic acid.    
6. 12038964: This relevant document reports that Rac is an essential component of the beta-amyloid signaling cascade leading to generation of reactive oxygen species.    
7. 12115629: This is a relevant document showing that Rac1 is required for the migration step of process formation of dendritic cells promoting cell spreading and extension.    
8. 12117911: This relevant document indicates that Rac is degraded by a proteasome-dependent pathway in CNF1-treated cells.    
9. 12169092: This relevant document shows that Rac1 and Cdc42 are novel signal transducers for SP-stimulated IL-8 expression.    
10. 12181570: This relevant document reports a mechanism by which Rac and the adapter protein Nck activate actin nucleation.    
11. 12239215: This relevant document reports on the effect of arsenic trioxide in inducing Rac1 activation in certain leukemia cell lines.    
12. 12376551: This relevant document reports that RhoG function is not mediated by Rac1 activation as previously thought.    
13. 12377770: This relevant document reported on a study that found that alphav integrin ligation activated small GTPase Rac1 preferentially, and dominant negative Rac1 inhibited alphav integrin-mediated p38 MAPK activation.    
14. 12393431: This relevant document observed Rac1 activation by IL-2 and found that it mediated PI 3-kinase activation of Akt that mediates natural killer cell survival.    
15. 12393632: This relevant document presents data to suggest the presence of a novel protein complex of CrkL, DOCK2, and Vav to regulate Rac1 in leukemia cell lines.    
16. 12453877: This relevant document presents results that suggest that Cdc42/Rac1-dependent activation of PAK may trigger early platelet shape change.    
17. 12524240: This relevant document reports on effects of Rac1 activation on endothelial cell senescence.    

Relevance of retrieved documents:
1. 12376551: See relevant GeneRIF 12 above    
2. 12070151: This relevant document reports on a study that indicates that M(3) mAChR activation converts Rac1 to the GTP-bound form, alters interactions between Rac1,    
3. 11973651: See relevant GeneRIF 4 above    
4. 12039869: This relevant document demonstrates a novel function of ref-1 in inhibition of rac1 activity, and rac1-mediated oxidative stress and injury.
5. 11900529: This relevant document reported on a study that characterized the effect of the insert deletion on Rac1 structure, thermodynamic stability, and the kinetics of nucleotide association.
6. 12499359:This relevant document reports that low density lipoprotein receptor-related protein (LRP-1) regulates two signaling proteins in the same cell (Rac1 and ERK), both of which may impact on cell migration.
7. 12213441: This relevant document presents the results of a study that suggest that Pak1 regulates dendrite initiation as a downstream effector of Rac1.
8. 12485852: This relevant paper reports that the inhibition of Rac1 or Cdc42 signaling leads to MAPK ERK activation via a pathway involving PI(3)K, Akt, Raf, and MEK, but not Ras.
9. 12524240: See relevant GeneRIF 17 above
10. 12110184: This relevant document reports on results of a study that indicates that Rac1/Cdc42 marks special cortical spots where the IQGAP1 and CLIP-170 complex is targeted, leading to a polarized microtubule array and cell polarization.
11. 12181570: See relevant GeneRIF 10 above
12. 11884513: See relevant GeneRIF 3 above
13. 12482591: This relevant document reports results of a study that indicates that  Cdc42 and Rac1 are essential for ATX-induced tumor cell motility in A2058 melanoma cells, and that PAK and FAK might be also involved in the process.
14. 12055095: This relevant document reports that Rac1 signaling protects adherens junctions from damage during ATP depletion.
15. 12194856: This relevant document reports the results of a study defining a role for Rac1 in regulating the rates of initiation and strengthening of cell-cell adhesion.
16. 12393632: See relevant GeneRIF 15 above
17. 11950936: This relevant document reports on Antigen-stimulated activation of phospholipase D1b by Rac1, ARF6, and PKCalpha in RBL-2H3 cells
18. 12049773: This relevant study describes the temporal and spatial patterns of expression of the Rho family member, rac, during the development of the amphibian, Xenopus laevis
19. 12381718: This relevant study showed that Cdc42 and Rac1 regulate late events in Salmonella typhimurium-induced interleukin-8 secretion from polarized epithelial cells.
20. 12370828: This relevant study reports that LC3 interacts with Sos1 and thereby negatively regulates the Sos1-dependent Rac1 activation leading to membrane ruffling

Topic 28

Species: Rattus norvegicus

Gene Name:
Early growth response 1 (egr 1)

Gene Function:
Rat nerve growth factor induced gene located on 18q has transcription factor activity and plays an important part in neuronal plasticity.

GeneRIFs:
     
1. 11870074: This relevant document reports that arterial intimal thickening following artery ligation is critically-dependent on the activation of Egr-1.    
2. 11973468: This relevant document reports on a study that gave insights into the differential regulation of egr-1, and facilitated approaches to the genetic manipulation of Egr-1-regulated neuronal systems.    
3. 12021067: This relevant study provides further support to the hypothesis that Egr-1 plays important roles in the pituitary-gonadal axis.    
4. 12025859: This relevant document reports on regulation of Egr transcription factors during cocaine treatment.    
5. 12111808: This relevant abstract reports that exposure to lead elevates induction of zif268 and Arc mRNA in rats after electroconvulsive shock: the involvement of protein kinase C.    
6. 12145054: This relevant document reported that Midazolam induces expression of c-Fos and EGR-1 by a non-GABAergic mechanism.    
7. 12486186: This relevant document refers to induction of hippocampal long-term potentiation during waking leads to increased extrahippocampal zif-268 expression during ensuing rapid-eye-movement sleep.    

Relevance of retrieved documents:
1. 12374773: This relevant document reports on the negative regulatory role of over expression of PLC gamma 1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts.
2. 12571843: This relevant study reports results that show that the enhanced expression of Egr-1 may regulate the activity of matrix metalloproteinases in synovial fibroblasts by enhancing the expression of the TIMP-1, -2, and -3 genes.
3. 12161260: This relevant study suggests a role of brain NGFI-A in the protective effect of hypoxic/ischemic preconditioning.
4. 12065847: This relevant review article reports on Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival.    
5. 12039067: This relevant document hypothesizes that Sp1 competes for Egr1 binding to the Egr elements on the LHbeta promoter and thus inhibits the ability of GnRH and Egr1 to activate the LHbeta promoter.    
6. 11870074: Relevant GeneRIF see 1 above    
7. 11773597: This relevant report showed that in contrast to their repression by AKT, c-myc, THBS1, and EGR1 were induced by PDGFbeta, indicating negative interference between elements upstream and downstream of AKT1 in the PDGFbeta signal transduction pathway
8. 12414521: This relevant document studied the over expression of genes due to ischemia after prostate gland biopsy. There were 41 statistically significant named over expressed genes at the 1-hour time point including early growth response 1 (EGR1).
9. 11803140: This relevant study used synthetic promoters based on radiation responsive CArG elements derived from the Early Growth Response 1 (Egr1) gene to promote activation after irradiation.
10. 11954047: This relevant document report study results giving a detailed description of the differential spatial and temporal modulation of NGFI-B and c-Fos expression in the striatum by acute methamphetamine treatment over time.
11. 12529383: This is a relevant document about dimer-specific potentiation of NGFI-B (Nur77) transcriptional activity by the protein kinase A pathway and AF-1-dependent coactivator recruitment.
12. 11830332: This relevant document reported on the early induction of the NGFI-B family genes after ischemia-reperfusion injury in rat and human livers.
13. 12031344: This relevant document compared spontaneous and light-evoked levels of the immediate-early gene protein ZIF268 (NGFI-A) in the Syrian hamster and C57BL/6J mouse suprachiasmatic nucleus
14. 12470865: This relevant document reports on Basal EGR-1 (zif268, NGFI-A, Krox-24) expression in developing striatal patches: role of dopamine and glutamate.
15. 12124440: This relevant document reports on results that may implicate CREB and EGR1 in independent or partially independent cholinergic signaling pathways involved in memory processes.
16. 12165491: This relevant document reports on thymocyte development in early growth response gene 1-deficient mice.
17. 12197474: This relevant study reports that EGF1 among others including ninety-nine previously known and forty poorly characterized or novel sequences, were increased more than two-fold by VEGF within twenty-four hours of stimulation.
18. 11973359: This relevant study noted that cDNA array identified the transcription factor early growth response factor 1 (Egr1) as a target gene for TGFbeta in late phases of the wound healing process.
19. 12496415: This is a relevant document that discusses induction of the early growth response gene 1 promoter by TCR agonists and partial agonists
20. 11909979: This relevant document showed that the transcription of egr1 in response to both mitogenic and stress stimuli, as well as stress-induced apoptosis, was unaffected in the MSK1/MSK2 double knockout.

Topic 35

Species: Drosophila melanogaster

Gene Name:
CG3599

Gene Function:
Fruit fly gene located on chromosome arm X, cytogenetic map 5E1, the protein in the domain Nitrilase/N-carbamyl-D-aminoacid amidohydrolase, has hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds. Two reported mutations here are lethal.

GeneRIF:
1.  11749055: This paper reports on the identification of the putative biotinidase gene in the insect and its corresponding amino acid sequence. The same 62-amino-acid region, which includes a cysteine and is an essential part of the active site of bacterial amidases and nitrilases, is highly conserved in all the mammalian and putative Drosophila biotinidases.

Relevance of retrieved documents:
1. 11931232: This does not appear to be relevant, discussing transvection genes in drosophilia.    
2. 12081288: This document is not relevant and discusses the effect of increased mass on human ability to hop on one foot.    
3. 12365305: This document is not relevant and reports on patient Internet services.    
4. 11970311: This non-relevant document discusses polymers and copolymers.    
5. 12099542: This document is not relevant. It discusses the efficacy and tolerability of various medicated ophthalmic gels containing medications used to treat glaucoma.    
6. 12381010: This non-relevant document reports on wastewater treatment and uses of toilets that do not mix urine with other substances flushed so that ammonia can be created.    
7. 12137026: This document is not relevant and again reports on polymers, this time on synthesis.        
8. 12111720: This not clearly relevant document reports on myoblast fusion in drosophilia    
9. 11839276: This non-relevant document provides a representative standard for the brain of D. melanogaster wild-type with means and variances for several aspects of its shape.    
10. 11721854: This non-relevant document reports on a fluorescent tracer developed that enabled sensitive detection of liquid enzyme additions to feeds.    
11. 12324479: This document is not relevant. It reports on the stability of RNA in blood specimens.    
12. 12162370: This document is not relevant and reports on a various rewarding strategies in a differential detection test.    
13. 12221246: This non-relevant document examines the effects of fortification and added sugars in the diets of young children.    
14. 12084415: This non-relevant document reports on a study of the treatment of Schizophrenia.    
15. 12386928: This not clearly relevant paper discusses the mechanism by which trans-splicing between two RNA molecules containing different coding regions is the normal mode in a Drosophila gene and results in many protein isoforms. The differences lie in alternative 3' exons encoded by different transcriptional units and spliced to the 5' common region by a surprising trans-splicing mechanism.    
16. 12373696: This non-relevant document discusses anesthesia effects of atracurium on retrobulbar blocks.    
17. 11841500: This non-relevant document reports on the Drosophila ATBP gene, a homologue for Sarcophaga (A+T)-stretch binding protein, located in the 20E region of chromosome X.    
18. 12072868 This non-relevant document reported on the Sociodemographic determinants of added sugar intake in preschoolers 2 to 5 years old.    
19. 12154100: This document is not relevant. It reports on the efficacy and tolerability of eplerenone, a selective aldosterone blocker, when added to existing antihypertensive therapy with an ACE inhibitor or an angiotensin II receptor blocker (ARB).    
20. 12111533: This not clearly relevant document discusses genetic and molecular mechanisms underlying circadian clock function in Drosophila melanogaster.

Topic 36

Species: Drosophila melanogaster

Gene Name:
Hopscotch

Gene Function:
Hop encodes a product with protein tyrosine kinase activity involved in cytokinesis.  It is inferred to be involved in many processes, most involved with the brain & sensory organs and embryo. These include the JAK-STAT cascade, cell proliferation, equater specification, establishment of ommatidial polarity and rotation, primary sex determination, eye morphogenesis, periodic partitioning, stem cell maintenance, and photoreceptor differentiation.

GeneRIFs:
1. 11752574: This relevant document demonstrates that hub cells express the ligand Unpaired (Upd), which activates the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway in adjacent germ cells to specify self-renewal and continual maintenance of the germ line stem cell population.    
2. 11752575: This relevant document is nearly identical to the above document.    
3. 11804783: This relevant document reports that the JAK/STAT pathway is required for border cell migration during Drosophila oogenesis.    
4. 11919715: This relevant document reports that the Hopscotch Jak kinase requires the Raf pathway to promote blood cell activation and differentiation in Drosophila    
5. 12441298: This relevant document reports results that provide the first example in which JAK/STAT signaling plays a required role in orienting cell rearrangement that elongates an epithelium    

Relevance of retrieved documents:
1. 12586062: This relevant documents reports that cyclin D-Cdk4 and cyclin E-Cdk2 regulate the Jak/STAT signal transduction pathway in Drosophila    
2. 11804783: See relevant GeneRIF above
3. 12194841: This relevant article documents a review  of Drosophila Jak/STAT signalling
4. 11983158: This is another relevant review of recent advances in the field and highlights some of the most active areas of Jak-Stat pathway research.
5. 12040185: Yet another relevant review article about JAK-STAT signaling pathways
6. 12423195: This non-relevant document reports on a study to determine the test-retest reliability of 4 single-leg horizontal hop tests    
7. 12479803: Once again a relevant review article of the JAK/STAT pathway,   this time emphasizing recent insights into the role that this pathway plays in the control of cell movement.    
8. 11837794: This is a relevant review article on Suppressors of cytokine signaling (SOCS): inhibitors of the JAK/STAT pathway
9. 12039028: Another relevant review article on exciting developments in JAK/STAT signaling. (Not DM)
10. 12204892: This relevant document shows that neuregulin-1 activates the JAK-STAT pathway and regulates lung epithelial cell proliferation. (human)
11. 12600939: This relevant document presents findings that identify UBP43 as a novel negative regulator of IFN signaling and suggest the involvement of protein ISGylation in the regulation of the JAK-STAT pathway. (mice)
12. 12095053: This relevant paper reports on a study that reported the effect of anti-IL-2Ralpha antibody on IL-2-induced Jak/STAT signaling. (human)    
13. 11919715: This relevant document showed that the Hopscotch Jak kinase requires the Raf pathway to promote blood cell activation and differentiation in Drosophila.
14. 12441298: This is relevant, see GeneRIF above
15. 12601549: This relevant document reports that hypermethylation is associated with inactivation of the SOCS-1 gene, a JAK/STAT inhibitor, in human hepatoblastomas. (human)
16. 12191995: This relevant document reports on a study that indicates that JAK-STAT signaling is an early event in gangliosides-induced brain inflammatory responses. (rat)
17. 12111345: This relevant document reports that the activation of APC in the early sensitization phase of contact hypersensitivity by haptens does not involve signals normally delivered by JAK-associated cytokine receptors. (human)
18. 12584581: This relevant document provides an overview of the current knowledge about JAK/STAT/SOCS intracellular signaling cascades with special emphasis on their abnormalities in cancer. (human)
19. 12003786: This relevant document discusses the role of the JAK-STAT pathway in PDGF-stimulated proliferation of human airway smooth muscle cells.
20. 11967010: This relevant document provides evidence that activation of the JAK/STAT pathway by HG or/and Ang II may be of importance in the increased GMC cell growth and collagen IV synthesis that is seen in diabetic nephropathy. (Human)

Topic 40

Species: Drosophila melanogaster

Gene Name:
Stat92E: Signal-transducer and activator of transcription protein at 92E

Gene Function:
DNA Binding, Transcription factor activity, primary sex determination, oogenesis, defense response, signal transduction, blastoderm segmentation, JAK-STAT cascade, eye morphogenesis, border cell migration, wing morphogenesis, stem cell renewal and maintenance, and hematopoiesis. It codes for the only STAT protein found in drosophilia.

GeneRIFs:
1. 11752574: This document is relevant. STAT is required in germ cells for germ line stem cell self-renewal.     
2. 11752575: This relevant document reports that the support cells of the hub signal to adjacent stem cells by activation of the JAK-STAT pathway, thereby defining a niche for stem cell self-renewal.    
3. 11779460: This relevant document reports that paracrine signaling through the JAK/STAT pathway activates invasive behavior of ovarian epithelial cells in Drosophila.
4. 11804783: This relevant document reports that the JAK/STAT pathway is required for border cell migration during Drosophila oogenesis.
5. 11846485: This document is relevant. The paper reports that Drosophila STAT protein, stat92E, regulates follicle cell differentiation during oogenesis.
6. 12183376: This document is relevant. The paper states that STAT, encoded by marelle (mrl; DStat92E), is essential for the gain-of-function mutant Tor (Tor(GOF)) to activate ectopic gene expression.
7. 12231627: This document is most likely relevant but it does not clearly state that it is referring to Drosophilia. It reports that negative regulation of STAT92E by an N-terminally truncated STAT protein derived from an alternative promoter site.
8. 12441298: These relevant results provide the first example in which JAK/STAT signaling plays a required role in orienting cell rearrangement that elongates an epithelium.

Relevance of retrieved documents:
1. 12231627: See relevant GeneRIF 7 above
2. 12101419: This relevant document reports genetic interactions that imply that SOCS36E can suppress activities of the JAK/STAT and EGF-R signalling pathways in the wing disc    
3. 11804783: See relevant GeneRIF 4 above    
4. 12586062: this relevant document shows that Cyclin D-Cdk4 (as well as Cyclin E-Cdk2) binds and regulates STAT92E protein stability suggesting that Cyclin D-Cdk4 and Cyclin E-Cdk2 play more versatile roles in Drosophila development.    
5. 12183376: See relevant GeneRIF 6 above.    
6. 12441298: See relevant GeneRIF 8 above    
7. 12586057: this relevant document reports that Cdk4 overexpression can bypass requirements for JAK but not STAT    
8. 11957560: This is not relevant. BTA stat is a rapid, urine-based test for bladder cancer.    
9. 12194841: This relevant article documents a review  of Drosophila Jak/STAT signalling
10. 11983158: This is another relevant review of recent advances in the field and highlights some of the most active areas of Jak-Stat pathway research.
11. 12354717: This non-relevant document studies the effects of pH in pediatric anesthesia    
12. 12040185: Yet another relevant review article about JAK-STAT signaling pathways.    
13. 12598237: This is another non-relevant study about anesthesia    using the pH stat method
14. 11908255: This is another non-relevant study of the BTA stat bladder cancer test    
15. 11798881: This non-relevant document reports on signal transducers and activators of transcription (STAT) pathway in thrombin induction of TIMP1 in human mesangial cells.    
16. 11837794: This relevant review article reviews cytokine/GF signaling by the JAK/STAT pathway among other topics.    
17. 12479803: Once again a relevant review article of the JAK/STAT pathway,   this time emphasizing recent insights into the role that this pathway plays in the control of cell movement.    
18. 11928762: This non-relevant document discusses optimizes the use of stat lab tests.
19. 12204892 This relevant document shows that neuregulin-1 activates the JAK-STAT pathway and regulates lung epithelial cell proliferation. (human)
20. 12600939: This relevant document presents findings that identify UBP43 as a novel negative regulator of IFN signaling and suggest the involvement of protein ISGylation in the regulation of the JAK-STAT pathway. (mice)

Topic 48

Species: Homo sapiens

Gene Name:
DNA cross-link repair 1C (PSO2 homolog, S. cerevisiae) Artemis

Gene Function:
This gene located on 10p produces a protein that when complexed with or phsophorylated by PRKDC starts enzymatic activities that are critical for the hairpin-opening step of V(D)J recombination and for the 5-prime and 3-prime overhang processing in nonhomologous DNA end joining.  . Mutations of this gene are associated with severe combined immunodeficiency with sensitivity to ionizing radiation.

GeneRIFs:
1. 11955432: This relevant report demonstrated that DNA-PKcs regulates Artemis by both phosphorylation and complex formation to permit enzymatic activities that are critical for the hairpin-opening step of V(D)J recombination and for the 5' and 3' overhang processing in nonhomologous DNA end joining.    
2. 12055248: This relevant document reports that A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking Native Americans.    
3. 12406895: This relevant document studies Radiosensitive SCID patients with Artemis gene mutations that shows a complete B-cell differentiation arrest at the pre-B-cell receptor checkpoint in bone marrow.    
4. 12569164: This relevant study shows Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis.
    
Relevance of retrieved documents:
1. 12406895: See relevant GeneRIF 3 above
2. 11955432: See relevant GeneRIF 1 above
3. 12055248: See relevant GeneRIF 2 above
4. 12569164: See relevant GeneRIF 4 above
5. 12504013: This relevant document reports that the Leaky Scid phenotype is associated with defective V(D)J coding end processing in Artemis-deficient mice.
6. 12169665: This relevant document states that ARTEMIS represents a so-far-unrecognized link between prokaryotic cell fission and chloroplast division.
7. 11955439: This relevant document reports that when complexed with the catalytic subunit of DNA-dependent protein kinase (DNA-PK(cs)), the recently discovered dsDNA break repair protein named Artemis acquires the ability to open hairpin DNA molecules in vitro.
8. 12224067: This relevant document demonstrates the feasibility of prenatal diagnosis and carrier detection for SCIDA in the families at risk as well as the availability of a rapid screening test for the SCIDA founder mutation that can be used in all Navajo and Apache newborns and at-risk fetuses.
9. 12007504: This non-relevant document reports on a study of HTLV-1 transformed cell lines in NOD/SCID mice that suggests that this is an effective animal model to investigate molecular determinants of HTLV-1 lymphomagenesis.
10. 12393672: This possibly relevant document suggests that thalidomide metabolism is required for its antimyeloma efficacy using a study with the scid-hu model.
11. 12194272: This relevant document discusses induction of DNA double strand breaks in scid cells by carbon ions.
12. 12384806: This non-relevant document examines rapid blood clearance of injected mouse IgG2a in SCID mice.
13. 12052502: This relevant document presents a study in mice with results that suggest that DNA protein kinase catalytic subunit (DNA-PKcs), deficiency of which causes SCID mutation, plays an important role in the stable transmission of a genome containing hypervariable tandem repeats to progeny in male germ cells.
14. 11980979: This non-relevant document reports that scid mice only contract murine variant pneumocystosis and postulate therefore that humans do not contract pneumocystosis from animals.
15. 12041610: This non-relevant document studies non-obese scid mice for this study of cysticercosis.
16. 12197892: This document is not relevant as it reports on an X linked variant scid.
17. 12597150: This possibly relevant document reports on inhibition of growth of human nasopharyngeal cancer xenografts in SCID mice by arsenic trioxide.
18. 12218126: This relevant document suggests that SCID DNA-dependent protein kinase deficiency not only reduces the efficiency of hairpin opening, but also may affect the specificity of hairpin nicking, as well as the efficiency of joining open coding ends. (mice)
19. 12383203: This possibly relevant document reports on the effects of human interleukin-18 and interleukin-12 treatment on human lymphocyte engraftment in NOD-scid mouse.
20. 12172649: This non-relevant document reports on an experimental model for human tooth growth that happened to use NOD/scid mice.