lactoferrin

diseaseor

functions

genes

(Dry eye)

Sjogren’s syndrome

(Dry mouth)

Chronic hepatitis C (HCV)

Colon polyp

Tinea pedis

Periodontal disease

Stomatitis

H. Pylori

Intestinal bacteria flora

Iron absorption

Apply of Textmining Method to Study the Roles in Improving the Healthby Lactoferrin, a Multi-Functional Milk Protein

Kei-ichi SHIMAZAKI1, Tatsuya KUSHIDA2, Koji YAMAUCHI3 and Toshihisa TAKAGI4

1Hokkaido University, Sapporo, 2NalaPro Technologies, Inc., Tokyo3Food Science & Technology Institute, Morinage Milk Co., Ltd., Zama

4Database Center for Life Science, ROIS, Tokyo

vascular endothelial growth factor (VEGF)

vascular endothelial growth factor receptor

(VEGFR1/2/3)

transcriptional factorproteolytic enzymesmetabolic enzymes

growthdifferentiationcell survivemigration

neovascularization(angiogenesis)

vascular endothelial cell

P

KDR

Nrp1/2

GRB2

Ras

And other pathwaysMAPK

PI3K

Akt

cancer

cell

SOS

ESR1

inhibit

control

interact

Lactoferrin

inhibit1)

activate2)

control3)

interact4)

bind5)

activate2)

bind6)

bind7)

bind9)

bind7,8)

1) Norrby,K., J Vas Res 41(4) 293 (2004)2) Kim et al., FEBS Lett 580(18) 4332 (2006)3) Stokes et al., J Mol Endocrinol 33(2) 315 (2004)4) Zaiteva et al., J Soc Gynecol Inv 11(8) 529 (2004)

Angiogenesis related substancesSubstances related withLactoferrin and angiogenesis

SummarySummary What isWhat isLactoferrinLactoferrin??

CollectionArticles byPubMed

ExtractionInteractionsby GENPAC

ManuallyCuration

by Experts

Visualizationof Networks

by Cytoscape*

Collection article sets arranged by disease (function) by PubMed usingMeSH Major Topic

Extraction interaction data arranged by disease (function) from the article set by GENPAC

Check and correction the data to reduce false positive data

Visualizing disease networks to assist understanding of the mechanism of diseases (function)

angiogenesis&

lactoferrin

angiogenesis&

lactoferrin

angiogenesis&

lactoferrin

angiogenesis&

lactoferrin

Information extraction byGENPAC

Four Step Process ofextracting lactoferrin network

Lactoferrin is a metal-binding glycoprotein found in milk, blood andother exocrine secretions. Lactoferrin is a multi-functional proteinthat exhibits many activities such as: anti-microbial, anti-viral,immunomodulatory, anti-inflammatory, anti-tumor, anti-metastatic,cell growth-promoting, and anti-oxidant activities, as well asregulation of granulopoiesis and iron absorption, etc.

Our purposeOur purpose

vascular endothelial growth factor (VEGF)

vascular endothelial growth factor receptor

(VEGFR1/2/3)

transcriptional factorproteolytic enzymesmetabolic enzymes

vascular endothelial cell

P

KDR

Nrp1/2

GRB2

Ras

And other pathwaysMAPK

PI3K

Akt

cancer

cell

SOS

ESR1

inhibit

control

interact

LactoferrinLactoferrin and andangiogenesisangiogenesis network network

AngiogenesisAngiogenesis pathway pathway

genesgene familiesstimulate/activatesuppress/inhibitcontrolInteraction/bind

interaction3)

ATP to cAMPinteraction2)

inhibit1)

1) Br J Nutr 91(4) 533 (2004)2) Biochim Biophys Acta 898(2) 137 (1987)3) J Invest Dermatol 117(6) 1635 (2001)

AtopicAtopic dermatitis map dermatitis map

inhibit1)

LTF

activate2)

activate3)

activate6)

activate5)

activate4)

activate7)

5) Mol Immunol 44(7) 1498 (2007)6) Inf Immun 70(4) 1860 (2002)7) Oral Microbiol Immunol 14(5) 1275 (1999)8) Br J Dermatol 138(2) 1277 (1998)

1) Blood 80(1)235 (1992)2) JBC 273(49) 32670 (1998)3) BBRC 290(1) 236 (2002)4) Infl Res 52(3) 111 (2003)

H. pyloriH. pylori’’ss attack attack

Network of Network of atopic atopic dermatitisdermatitis& related substances& related substances

Map of Map of Lactoferrin Lactoferrin &&H. pylori networksH. pylori networks

Possible participation maps of Possible participation maps of lactoferrin lactoferrin against against angiogenesisangiogenesis, , atopic atopic dermatitis & dermatitis & H. pyloriH. pylori

Akt, Ser/Thr kinase; GRB2, growth factor receptor-bound protein2; KDR, kinase insert domain-containing receptor; MAPK, mitogen-activatedprotein kinase; Nrp, neuropilin receptor; PI3K,phosphatidylinositol-3-kinase; Ras, rat sercoma viraloncogene (small GTPase); SOS, guaninenucleotide-exchange factor (GEF)

Effecttiveness oflactoferrin

orally adninisteredTo date, a number of academic reports concerning the biologicalactivities of lactoferrin have been published and are easilyaccessible through public databases. In order to overcome theinformation overload associated with lactoferrin information, wehave applied the text mining method to the accumulated lactoferrinliterature. To this end, we used the information extraction systemGENPAC (provided by Nalapro Technologies Inc., Tokyo), whichuses natural language processing and text mining technology.Using GENPAC, text extraction was carried out on literaturecontaining the term "lactoferrin" and any of keywords concerninghealth conditions or diseases from PubMed. Subsequently,network mappings of the information obtained were produced usingCytoscape.In this poster, we show three examples of lactoferrin’s functionalpathways estimated by the textmining method. They are“lactoferrin and angiogenesis pathways”, “possible participation oflactoferrin against H. pylori’s attack” and “possible participations oflactoferrin and flavonoid against atopic dermatitis”.