Chemical Informatics and Chemical Informatics and Bioinformatics Programs at Bioinformatics Programs at

Indiana UniversityIndiana UniversityGary WigginsGary Wiggins

School of InformaticsSchool of InformaticsIndiana UniversityIndiana University

ACS, Philadelphia, 23 August 2004ACS, Philadelphia, 23 August 2004

OverviewOverview

Comments on Chemical Informatics as a Comments on Chemical Informatics as a DisciplineDiscipline

Other Programs and CoursesOther Programs and Courses Indiana University ProgramsIndiana University ProgramsProblemsProblemsBioinformatics ProgramsBioinformatics ProgramsFutureFuture

Comments on Chemical Informatics Comments on Chemical Informatics as a Disciplineas a Discipline

JJüürgen Bajorath on rgen Bajorath on Chemoinformatics, etc.Chemoinformatics, etc.

Chem-, chemi-, or chemo-informaticsChem-, chemi-, or chemo-informaticsFocus on the information resources needed to Focus on the information resources needed to

optimize the properties of a ligand to become optimize the properties of a ligand to become a drug (Frank Brown, 1998)a drug (Frank Brown, 1998)Decision support by computational meansDecision support by computational meansDrug discoveryDrug discovery

Chemical Informatics: the application of Chemical Informatics: the application of information technology to chemistry (not information technology to chemistry (not with a specific focus on drug discovery)with a specific focus on drug discovery)

Related Terms per BajorathRelated Terms per Bajorath

ChemometricsChemometricsApplication of statistical methods to chemical Application of statistical methods to chemical

data and the derivation of relevant statistical data and the derivation of relevant statistical models and descriptorsmodels and descriptors

Increasingly difficult to distinguish between Increasingly difficult to distinguish between chemometrics and chemoinformaticschemometrics and chemoinformatics

Discovery informatics—acknowledges that Discovery informatics—acknowledges that gaining knowledge from chemical data gaining knowledge from chemical data alone is insufficient for success in drug alone is insufficient for success in drug discoverydiscovery

Bajorath’s ConclusionsBajorath’s Conclusions

Boundaries between bioinformatics and Boundaries between bioinformatics and chemoinformatics are fluidchemoinformatics are fluidBoth should be closely combined or merged Both should be closely combined or merged

to significantly impact biotechnology or to significantly impact biotechnology or pharmaceutical researchpharmaceutical research

Bajorath, JBajorath, Jüürgen, Ed. rgen, Ed. Chemoinformatics: Concepts, Methods, and Tools for Chemoinformatics: Concepts, Methods, and Tools for Drug Discovery.Drug Discovery. (Methods in Molecular Biology; 275) Humana Press: (Methods in Molecular Biology; 275) Humana Press: Totawa, NJ, 2004.Totawa, NJ, 2004.

Other Programs and CoursesOther Programs and Courses

Another Program in the USAnother Program in the US

University of Massachusetts, LowellUniversity of Massachusetts, LowellMS in Computer Science with an option in MS in Computer Science with an option in

Bio/CheminformaticsBio/CheminformaticsPrescribed courses for 30 hours (assuming all Prescribed courses for 30 hours (assuming all

prerequisites met)prerequisites met)Thesis may count for 6 of the hoursThesis may count for 6 of the hoursRepesentative course: Selected topics in Repesentative course: Selected topics in

Chemistry: Protein and Chemical InformaticsChemistry: Protein and Chemical InformaticsAlso offer a Doctor of Science degreeAlso offer a Doctor of Science degreehttp://http://genome.uml.edu/programs_grad.htmgenome.uml.edu/programs_grad.htm

Selected Courses in Selected Courses in CheminformaticsCheminformatics

Introduction to Chemoinformatics Course at the Introduction to Chemoinformatics Course at the University of MichiganUniversity of Michigan Offered through the interdisciplinary program in Pharmaceutical Offered through the interdisciplinary program in Pharmaceutical

EngineeringEngineering Taught by David WildTaught by David Wild http://www-personal.engin.umich.edu/~wildd/chemoinf/http://www-personal.engin.umich.edu/~wildd/chemoinf/

index.htmlindex.html Chemoinformatics Course at The Danish University of Chemoinformatics Course at The Danish University of

Pharmaceutical SciencesPharmaceutical Scienceshttp://www.dfh.dk/phd/courses/descriptions/courses20042005/http://www.dfh.dk/phd/courses/descriptions/courses20042005/

chemoinformatics.htmchemoinformatics.htm Analytical Informatics at Purdue (Randy Julian)Analytical Informatics at Purdue (Randy Julian)

http://http://miner.chem.purdue.eduminer.chem.purdue.edu//

Bogus Programs???Bogus Programs???

Institute of Cheminformatics StudiesInstitute of Cheminformatics Studies

http://www.cheminformaticscentre.org/chem/http://www.cheminformaticscentre.org/chem/ NC State University Certified Bioinformatics NC State University Certified Bioinformatics

Specialist: CheminformaticsSpecialist: Cheminformatics

http://www.ncsu.edu/ctu/documents/pdfdocs/markhttp://www.ncsu.edu/ctu/documents/pdfdocs/marketingpackets/biochembrochure.pdfetingpackets/biochembrochure.pdf Chemoinformatics National BioInformatics Chemoinformatics National BioInformatics

InstituteInstitute

http://www.bioinfoinstitute.com/chemoinfo.htmhttp://www.bioinfoinstitute.com/chemoinfo.htm

Indiana University Programs in Indiana University Programs in Chemical InformaticsChemical Informatics

Specialized Chemistry Degree Options Specialized Chemistry Degree Options at Indiana Universityat Indiana University

BS in Informatics with a chemistry or biology BS in Informatics with a chemistry or biology cognate (essentially a minor)cognate (essentially a minor)

MS in Chemical InformaticsMS in Chemical Informatics MS in BioinformaticsMS in Bioinformatics PhD in Science Informatics (expected Fall 2005)PhD in Science Informatics (expected Fall 2005)http://http://www.informatics.indiana.eduwww.informatics.indiana.edu

MLS or MIS with a specialization in chemical MLS or MIS with a specialization in chemical informationinformation

http://www.slis.indiana.eduhttp://www.slis.indiana.edu

IU’s MS in Chemical InformaticsIU’s MS in Chemical Informatics

Developed jointly by the School of Developed jointly by the School of Informatics and chemistry departments at Informatics and chemistry departments at IUB and IUPUIIUB and IUPUI

First students admitted at IUPUI in fall First students admitted at IUPUI in fall 2001 and at IUB in fall 20022001 and at IUB in fall 2002

Graduates: 4Graduates: 4Currently enrolled: 11Currently enrolled: 11

Unique Program at IUPUIUnique Program at IUPUI

Laboratory Informatics track at IUPUILaboratory Informatics track at IUPUI Instrumentation and data interfacingInstrumentation and data interfacingLaboratory notebooksLaboratory notebooksLaboratory Information Management Systems Laboratory Information Management Systems

(LIMS)(LIMS)

Why IU for Chemical Informatics?Why IU for Chemical Informatics?

Outstanding FacultyOutstanding Faculty Excellent computer facilities and infrastructureExcellent computer facilities and infrastructure Close proximity to major pharmaceutical Close proximity to major pharmaceutical

companies (Lilly, Abbott, Pfizer) and to chemical companies (Lilly, Abbott, Pfizer) and to chemical informatics companies (Tripos, LeadScope, informatics companies (Tripos, LeadScope, Chemical Abstracts Service)Chemical Abstracts Service)

History of innovative, IT-based chemical History of innovative, IT-based chemical information services (QCPE, MSC)information services (QCPE, MSC)

Well-established programs in IU’s SLISWell-established programs in IU’s SLIS

Core and Affilated Faculty at IUBCore and Affilated Faculty at IUB

MU-HYUN (MOOKIE) BAIKMU-HYUN (MOOKIE) BAIK SANTIAGO SCHNELLSANTIAGO SCHNELL DAVID WILDDAVID WILD (visiting) (visiting) DIMITRIS AGRAFIOTIS DIMITRIS AGRAFIOTIS (adjunct)(adjunct) JOHN BARNARD JOHN BARNARD (adjunct)(adjunct) JOHN C. HUFFMANJOHN C. HUFFMAN (adjunct) (adjunct) GEORGE W. A. MILNE GEORGE W. A. MILNE (adjunct)(adjunct) PETER ORTOLEVA PETER ORTOLEVA (adjunct)(adjunct) GARY WIGGINSGARY WIGGINS (adjunct) (adjunct) KEVIN GILBERTKEVIN GILBERT (affiliated) (affiliated) CHARLES H. DAVISCHARLES H. DAVIS (affiliated) (affiliated)

Core and Affilated Faculty at IUPUICore and Affilated Faculty at IUPUI

SAM A.F. MILOSEVICHSAM A.F. MILOSEVICHMAHESH MERCHANTMAHESH MERCHANTJOHN MCKELVEYJOHN MCKELVEY (adjunct) (adjunct)DON BOYDDON BOYD (affiliated) (affiliated)KELSEY FORSYTHEKELSEY FORSYTHE (affiliated) (affiliated)

Outreach ActivitiesOutreach Activities

Research relationships withResearch relationships with IU School of MedicineIU School of Medicine IUB/IUPUI bioinformatics and proteomics IUB/IUPUI bioinformatics and proteomics

research programsresearch programsCommercial firms through internships Commercial firms through internships

(LeadScope, Rosetta Inpharmatics, Lilly)(LeadScope, Rosetta Inpharmatics, Lilly)

IU Undergraduate CoursesIU Undergraduate Courses

Four one-credit undergrad coursesFour one-credit undergrad coursesC371 Chemical Informatics IC371 Chemical Informatics IC372 Chemical Informatics II: Molecular C372 Chemical Informatics II: Molecular

ModelingModelingC471 Chemical Information Sources and C471 Chemical Information Sources and

ServicesServicesC472 Computer Sources for Chemical C472 Computer Sources for Chemical

InformationInformation

IU Graduate CoursesIU Graduate Courses

Two three-credit graduate coursesTwo three-credit graduate coursesC571 Chemical Information TechnologyC571 Chemical Information TechnologyC572 Molecular Modeling & Computational C572 Molecular Modeling & Computational

ChemistryChemistryNew courses under developmentNew courses under development

Programming for Chemical InformaticsProgramming for Chemical Informatics Information Retrieval from Chemistry and Life Information Retrieval from Chemistry and Life

Sciences DatabasesSciences Databases

Tools Used or Planned for UseTools Used or Planned for Use SpotfireSpotfire ChemTK LiteChemTK Lite Chemaxon’s MarvinChemaxon’s Marvin Chemical Computing Group’s MOEChemical Computing Group’s MOE Daylight ToolkitDaylight Toolkit OpenEye (all modules)OpenEye (all modules) BCI softwareBCI software WaveFunction’s SpartanWaveFunction’s Spartan Serena Software’s PCModelSerena Software’s PCModel [MDL DiscoveryGate for Academics][MDL DiscoveryGate for Academics]

Sharing InstructionSharing Instruction

ProblemsProblems

ProblemsProblems

Competition for students from established Competition for students from established chemistry graduate programschemistry graduate programs

Lack of financial support for the studentsLack of financial support for the studentsLack of a PhD programLack of a PhD programWhat to teach in this huge fieldWhat to teach in this huge fieldLack of background in the discipline on the Lack of background in the discipline on the

part of the studentspart of the students

Problem: Students with Little or No Problem: Students with Little or No Background in Science or CSBackground in Science or CS

Often MS students have good computer science Often MS students have good computer science background, but little or no science training or vice versabackground, but little or no science training or vice versa

Solution: Remedial coursesSolution: Remedial courses Chemical Foundation for BioinformaticsChemical Foundation for Bioinformatics

http://www.poly.edu/catalog03-05/catalog03-05-21-bioinformatics.pdfhttp://www.poly.edu/catalog03-05/catalog03-05-21-bioinformatics.pdf Polytechnic University (Brooklyn)Polytechnic University (Brooklyn)

Introduction to GenomicsIntroduction to Genomics Indiana UniversityIndiana University

A-level graduate courses in Computer ScienceA-level graduate courses in Computer Science Indiana UniversityIndiana University

Dilemma: Should remedial courses count toward the MS Dilemma: Should remedial courses count toward the MS degree?degree?

Problem: Little exposure to Problem: Little exposure to chemical informatics as undergradschemical informatics as undergradsCan a student really master chemical Can a student really master chemical

informatics in a 1- or 2-year MS program?informatics in a 1- or 2-year MS program?

Huge Size of the Chemical Huge Size of the Chemical LiteratureLiterature

~ 50 million chemical substances~ 50 million chemical substances~ 6 million reagents~ 6 million reagents~ 7 million published reactions~ 7 million published reactions~16,000 protein crystal structures~16,000 protein crystal structures~250,000 small molecule x-ray structures~250,000 small molecule x-ray structures

Glen, Robert; Aldridge, Susan. “Developing tools and standards in molecular Glen, Robert; Aldridge, Susan. “Developing tools and standards in molecular informatics.” informatics.” Chemical CommunicationsChemical Communications 20022002, , (23),(23), 2745-2747. DOI: 2745-2747. DOI: 10.1039/b207793k10.1039/b207793khttp://http://xlink.rsc.orgxlink.rsc.org/?DOI=b207793k/?DOI=b207793k

BioinformaticsBioinformatics

IU Bioinformatics ProgramsIU Bioinformatics Programs

Also started in 2001Also started in 2001Approximately 50 students in the program Approximately 50 students in the program

between the two campusesbetween the two campusesNine degrees awarded to dateNine degrees awarded to dateEmphasis on the computer science side of Emphasis on the computer science side of

the fieldthe fieldRecently recruited seven new faculty with Recently recruited seven new faculty with

research interests in bioinformaticsresearch interests in bioinformatics

Bioinformatics Faculty at IUBBioinformatics Faculty at IUB SUN KIMSUN KIM MEHMET (MEMO) DALKILICMEHMET (MEMO) DALKILIC HAIXU TANGHAIXU TANG ALESSANDRO FLAMMINIALESSANDRO FLAMMINI ALESSANDRO VESPIGNANIALESSANDRO VESPIGNANI LUIS MATEUS ROCHALUIS MATEUS ROCHA SANTIAGO SCHNELLSANTIAGO SCHNELL LARRY YAEGERLARRY YAEGER PETER CHERBASPETER CHERBAS (adjunct) (adjunct) JAMES GLAZIERJAMES GLAZIER (adjunct) (adjunct) ALEXANDER BOLSHOYALEXANDER BOLSHOY (visiting) (visiting) PREDRAG RADIVOJACPREDRAG RADIVOJAC (visiting) (visiting)

Bioinformatics Faculty at IUPUIBioinformatics Faculty at IUPUI

A. KEITH DUNKERA. KEITH DUNKERARIEL FERNANDEZARIEL FERNANDEZJEFFREY HUANGJEFFREY HUANGSNEHASIS MUKHOPADHYAYSNEHASIS MUKHOPADHYAYNARAYAN PERUMALNARAYAN PERUMAL (visiting) (visiting)MALIKA MAHOUIMALIKA MAHOUI (visiting) (visiting)ZINA BEN-MILEDZINA BEN-MILED (adjunct) (adjunct)

Directories: bio1nf0rm Directories: bio1nf0rm (US only)(US only)

64 programs listed64 programs listed Degrees range from dedicated programs to Degrees range from dedicated programs to

specialized tracks within computer science or specialized tracks within computer science or biology departments biology departments

3 of the 64 began accepting students in 2003, 3 of the 64 began accepting students in 2003, compared to 14 in 2002 and 17 in 2001compared to 14 in 2002 and 17 in 2001 Over half of the programs began in the last three Over half of the programs began in the last three

years!years!

Survey: Bio1nf0rm 2003Survey: Bio1nf0rm 2003

44 MS programs awarded 117 degrees44 MS programs awarded 117 degrees46 PhD programs awarded 35 degrees46 PhD programs awarded 35 degreesSeven schools have all three levels of Seven schools have all three levels of

programsprogramsGraduates: 201 in 2003, 181 in 2002, 53 in Graduates: 201 in 2003, 181 in 2002, 53 in

2001 (BS, MS, or PhD)2001 (BS, MS, or PhD)60% are male; 40% are female60% are male; 40% are female

UKeU: UK eUniversities WorldwideUKeU: UK eUniversities Worldwide

Established in 2001Established in 2001For students anywhere in the worldFor students anywhere in the worldHas a global service support Has a global service support

infrastructure - available 24x7 infrastructure - available 24x7 http://www.ukeu.com/index.php?site=http://www.ukeu.com/index.php?site=

UKeU MSc in BioinformaticsUKeU MSc in Bioinformatics

University of Leeds and University of University of Leeds and University of ManchesterManchester

Next start date: 4 October 2004Next start date: 4 October 2004Duration: 1 ½ years at part-timeDuration: 1 ½ years at part-timeRequirements: Undergraduate degree in Requirements: Undergraduate degree in

any discipline and proficiency in Englishany discipline and proficiency in EnglishFee: GBP 9,000Fee: GBP 9,000 http://www.ukeu.com/courses/bioinformatics/courses_bioinformatics.php?site=studentshttp://www.ukeu.com/courses/bioinformatics/courses_bioinformatics.php?site=students

Indiana InitiativesIndiana Initiatives

Indiana Genomics InitiativeIndiana Genomics Initiativehttp://www.ingen.iu.edu/http://www.ingen.iu.edu/

Inproteo (Indiana Proteomics Consortium)Inproteo (Indiana Proteomics Consortium)http://www.inproteomics.com/index.htmlhttp://www.inproteomics.com/index.html

Bio Crossroads (Central Indiana Life Bio Crossroads (Central Indiana Life Science Network)Science Network)http://www.biocrossroads.com/default.htmhttp://www.biocrossroads.com/default.htm

Indiana University’s Indiana University’s Bioinformatics Initiatives: IndyBioinformatics Initiatives: Indy

Center for Computational Biology and Center for Computational Biology and Bioinformatics at IndianapolisBioinformatics at Indianapolis

http://www.compbio.iupui.edu/http://www.compbio.iupui.edu/

Indiana University’s Indiana University’s Bioinformatics Initiatives: IUBBioinformatics Initiatives: IUB

Center for Genomics and BioinformaticsCenter for Genomics and Bioinformatics http://cgb.indiana.edu/http://cgb.indiana.edu/

Biocomplexity InstituteBiocomplexity Institute http://biocomplexity.indiana.edu/http://biocomplexity.indiana.edu/

Proteomics Research and Development FacilityProteomics Research and Development Facility http://www.chem.indiana.edu/facilities/proteomics/http://www.chem.indiana.edu/facilities/proteomics/

PRDFhomepage.htmPRDFhomepage.htm Flybase Drosophila Genome DatabaseFlybase Drosophila Genome Database

http://flybase.bio.indiana.edu/http://flybase.bio.indiana.edu/

FutureFuture

FutureFuture Implement the PhD program in science informaticsImplement the PhD program in science informatics Aggressively recruit students to both the MS and PhD Aggressively recruit students to both the MS and PhD

programsprograms Recruit additional facultyRecruit additional faculty Seek additional financial support for studentsSeek additional financial support for students Move into distance educationMove into distance education Forge additional partnerships with the chemical, Forge additional partnerships with the chemical,

bioscience, and pharmaceutical industries, with chemical bioscience, and pharmaceutical industries, with chemical and bioiscience informatics and other relevant software and bioiscience informatics and other relevant software and database companiesand database companies

Work closely with the newly formed Science Informatics Work closely with the newly formed Science Informatics Advisory BoardAdvisory Board

School of InformaticsSchool of InformaticsScience Informatics Advisory BoardScience Informatics Advisory Board

(as of 8/19/2004)(as of 8/19/2004)

Esther Allen (Consultant; formerly, MDL)Esther Allen (Consultant; formerly, MDL) Malorye Branco (Bio-IT WorldMalorye Branco (Bio-IT World Caroline Kovac (IBM Healthcare and Life Sciences)Caroline Kovac (IBM Healthcare and Life Sciences) Rudy Potenzone, Sr. (Ingenuity Systems)Rudy Potenzone, Sr. (Ingenuity Systems) Lura Powell (AIT, Advanced Imaging TechnologiesLura Powell (AIT, Advanced Imaging Technologies John Reynders (Eli Lilly & Co.)John Reynders (Eli Lilly & Co.) Richard A. Roberts (Pfizer)Richard A. Roberts (Pfizer) Ray Salemme (Linguagen; formerly, 3DP)Ray Salemme (Linguagen; formerly, 3DP) Mick Savage (Consultant; formerly MSI, now Accelrys)Mick Savage (Consultant; formerly MSI, now Accelrys)

Thanks to Graduate Fellowship Thanks to Graduate Fellowship Sponsors:Sponsors:

Daylight Chemical Information SystemsDaylight Chemical Information Systems

MDL Information SystemsMDL Information Systems

BibliographyBibliography Calandra, Bob. “Bioinformatics knowledge vital to Calandra, Bob. “Bioinformatics knowledge vital to

careers.” careers.” The ScientistThe Scientist September 2, 2002September 2, 2002, 16(17). , 16(17). http://www.thescientist.com/yr2002/sep/prof1_020902.hthttp://www.thescientist.com/yr2002/sep/prof1_020902.htmlml

Ham, Becky. “Bioinformatics.” Ham, Becky. “Bioinformatics.” ChemistryChemistry Winter 2004Winter 2004, , 9-10.9-10. http://www.chemistry.org/portal/a/c/s/1/acsdisplay.html?http://www.chemistry.org/portal/a/c/s/1/acsdisplay.html?DOC=Chemistry%5Cindex.htmlDOC=Chemistry%5Cindex.html

Harmon, G.; Garfield, E.; Paris, G. et al.Harmon, G.; Garfield, E.; Paris, G. et al. “ “Bioinformatics Bioinformatics in information science education.” Proceedings of the in information science education.” Proceedings of the ASIST Annual Meeting ASIST Annual Meeting 20022002, , 3939, 490-491., 490-491.

Henry, Celia M. “Careers in bioinformatics.” Henry, Celia M. “Careers in bioinformatics.” Chemical & Chemical & Engineering NewsEngineering News April 8, 2002April 8, 2002, , 80(14),80(14), 83-84, 86. 83-84, 86.

Bibliography (cont’d)Bibliography (cont’d) Russo, Eugene. “Chemistry plans a structural overhaul.” Russo, Eugene. “Chemistry plans a structural overhaul.”

NatureNature September 12, 2002September 12, 2002, , 419(6903), 419(6903), J4-J7. DOI: J4-J7. DOI: http://dx.doi.org/10.1038/nj6903-04ahttp://dx.doi.org/10.1038/nj6903-04a

Schofield, Helen; Wiggins, Gary; Willett, Peter. "Recent Schofield, Helen; Wiggins, Gary; Willett, Peter. "Recent developments in chemoinformatics education." developments in chemoinformatics education." Drug Drug Discovery TodayDiscovery Today September 2001September 2001, , 6(18),6(18), 931-934. 931-934.

Toner, Bernadette. “Number of bioinformatics grads Toner, Bernadette. “Number of bioinformatics grads grows, but rise in degree programs slows in 2003.” grows, but rise in degree programs slows in 2003.” bio1nf0rmbio1nf0rm August 11, 2003August 11, 2003, , 7(32),7(32), 1, 6-10. 1, 6-10.

Wiggins, Gary. “Teaching chemical literature, databases, Wiggins, Gary. “Teaching chemical literature, databases, and chemical informatics.” CPT; Committee on and chemical informatics.” CPT; Committee on Professional Training [newsletter] Professional Training [newsletter] Spring 2004Spring 2004, , 4(1),4(1), 1-2. 1-2.http://www.chemistry.org/portal/resources/ACS/http://www.chemistry.org/portal/resources/ACS/

ACSContent/education/cpt/nl_cpt_spring2004.pdfACSContent/education/cpt/nl_cpt_spring2004.pdf

Chemical Informatics TextbooksChemical Informatics Textbooks

Leach, Andrew R.; Gillet, Valerie J. An Leach, Andrew R.; Gillet, Valerie J. An Introduction to Chemoinformatics. Kluwer, 2003. Introduction to Chemoinformatics. Kluwer, 2003. ISBN 1-4020-1347-7 ISBN 1-4020-1347-7

Gasteiger,Johann;Engel, Thomas. Gasteiger,Johann;Engel, Thomas. Chemoinformatics: A Textbook. Wiley-VCH, Chemoinformatics: A Textbook. Wiley-VCH, 2003. ISBN 3-527-30681-12003. ISBN 3-527-30681-1

Bajorath, JBajorath, Jürgen, Ed. ürgen, Ed. Chemoinformatics: Chemoinformatics: Concepts, Methods, and Tools for Drug Concepts, Methods, and Tools for Drug Discovery.Discovery. (Methods in Molecular Biology; 275) (Methods in Molecular Biology; 275) Humana, 2004. ISBN 1-58829-261-4Humana, 2004. ISBN 1-58829-261-4