Bioinformatics Director Lecture University of Michigan Medical School February 7, 2000 Building Analysis Environments Beyond the Genome and the Web Bruce R. Schatz CANIS Laboratory School of Library & Information Science School of Biomedical & Health Information Sciences University of Illinois at Urbana-Champaign

Technological Progress In the past decade, technology has created the Genome and the Web In 1990, these ideas were only plans In 2000, they have already progressed from research systems to commercial products In the next decade, the revolution will actually begin and the world will be completely different!

Paradigm Shift Towards Dry-Lab Biology, Walter Gilbert (Jan 1991) “The new paradigm, now emerging, is that all the 'genes' will be known (in the sense of being resident in databases available electronically), and that the starting point of a biological investigation will be theoretical. An individual scientist will begin with a theoretical conjecture, only then turning to experiment to follow or test that hypothesis.... To use this flood of knowledge [the total sequence of the human and model organisms], which will pour across the computer networks of the world, biologists not only must become computer-literate, but also change their approach to the problem of understanding life.... The Coming of Informational Science Correlation of Knowledge across Sources

Analysis Environments I The Present -- Year 2000 Search Central Archives Locating a Generic (average) solution mining sequences from the Genome diagnosing diseases from the Clinical Trial some Problems may have point Solutions find the cystic fibrosis gene find the diabetes treatment

Analysis Environments II The Future -- Year 2010 Navigate Distributed Repositories Locating a Specific (situational) solution correlating sequences, genes, expressions correlating diagnoses, treatments, lifestyles most Problems have cluster Solutions find genes for Heart Disease find treatments for Arthritis

WCS -- a testbed for the world of 2000 community repositories before the Web in 1991, a distributed analysis environment MIBI -- a testbed for the world of 2010 concept navigation before the Interspace in 2001, a biomedical analysis environment to enable Michigan faculty and students to live in the world of the future Testbeds of the Future

Bioinformatics[basic] Scientific. Biology: genetics, genomics. Medical Informatics[translational] Clinical. Medicine: literature, records. Healthcare Informatics[management] Practical. Outcomes: tracking, quality. The Kinds of Informatics

Community Systems browse and share all the knowledge of a community data results (database management)(electronic mail) literature news (information retrieval) (bulletin boards ) knowledge (hypertext annotations) Formal Informal

Worm Community System WCS Information: Literature BIOSIS, MEDLINE, newsletters, meetings Data Genes, Maps, Sequences, strains, cells WCS Functionality Browsingsearch, navigation Filteringselection, analysis Sharinglinking, publishing WCS: 250 users at 50 labs across Internet (1991)

WCS Molecular

WCS Cellular

WCS invokes gm

WCS vis-à-vis acedb

WCS PPCS demo

A Model Community Telesophy (Bellcore) prototype to federate objects WCS (Arizona) testbed in molecular biology National Model for Biomedical Informatics NAS National Collaboratories report NIH Human Brain project Translational Results NCSA Mosaic into Web browsers acedb (worm) into Genome databases Biology Workbench, 10K users across Web

THE THIRD WAVE OF NET EVOLUTION PACKETS OBJECTS CONCEPTS

from Objects to Concepts from Syntax to Semantics Infrastructure is Interaction with Abstraction Internet is packet transmission across computers Interspace is concept navigation across repositories Towards the Interspace

Scalable Semantics Automatic indexing Domain-Independent indexing Statistical clustering Compute Context of concepts within documents documents within repositories

CROSS-OVERS IN SEMANTIC INDEXING

COMPUTING CONCEPTS ‘92: 4,000 (molecular biology) ‘93: 40,000 (molecular biology) ‘95: 400,000 (electrical engineering) ‘96: 4,000,000 (engineering) ‘98: 40,000,000 (medicine)

Simulating a New World Obtain discipline-scale collection MEDLINE from NLM, 10M bibliographic abstracts human classification: Medical Subject Headings Partition discipline into Community Repositories 4 core terms per abstract for MeSH classification 32K nodes with core terms (classification tree) Community is all abstracts classified by core term 40M abstracts containing 280M concepts concept spaces took 2 days on NCSA Origin 2000 Simulating World of Medical Communities 10K repositories with > 1K abstracts (1K w/ > 10K)

Concept Navigation Semantic Indexes for Community Repositories Navigating Abstractions within Repository concept space category map Interactive browsing by Community experts

Interspace Remote Access Client

Navigation in MEDSPACE For a patient with Rheumatoid Arthritis Find a drug that reduces the pain (analgesic) but does not cause stomach (gastrointestinal) bleeding Choose Domain

Concept Search

Concept Navigation

Retrieve Document

Navigate Document

Retrieve Document

Concept Switching In the Interspace… each Community maintains its own repository Switching is navigating Across repositories use your specialty vocabulary to search another specialty

Biomedical Session

Categories and Concepts

Concept Switching

Document Retrieval

Towards A Model Discipline Interspace (Illinois, Urbana) prototype to federate concepts MEDSPACE (Illinois, Chicago) testbed in clinical medicine (plan, demo) National Model for Biomedical Informatics lead news in Science on MEDLINE dry-run Best Paper at AMIA (Medical Informatics) MIBI (Michigan) testbed in biomedical research

Michigan Interspace Gather the Information Sources Michigan Integrated Biomedical Interspace (MIBI) each (department, institute, lab) has repository Generate the Community Repositories text documents with articles and annotations specialty datatypes: databases and motifs Construct the Analysis Environment federated concept switching across sites type-dependent parsing for text/data interlinks

MIBI Sources Literature Journals: MEDLINE, BIOSIS, fulltext Specialty Conferences (e.g. Neuroscience) Community Newsletters, Lab Annotations Databases Sequences: GENBANK, Celera Genes and Maps from Model Organisms Expressions from Microarrays Gene Pathways, Cellular Anatomy

U-M Medical School Testbed Department by Department Propagation Similar to Illinois Digital Library Testbed for College of Engineering at UIUC NSF DLI, , then University Library Federated Search using Document Structure Full-text Journals used in classes and labs

U-M Health System Testbed Central Propagation to Hospital and Clinics Similar to UIC Medical Center Testbed pilot project for Surgery residents after seed, planned to all Medical Center Concept Spaces for Community Repositories All Medical Literature (MEDLINE, BIOSIS) All Medical Records (Cerner narratives)

Chronic Illness Aging Population is Economics of 21st century Interspace is worldwide infrastructure Baby Boomers start retirement age Process for Health Status Frequency twice a yearcommunity clinic twice a month alternative medicine twice a dayself-care home monitors Arthritis versus Modern Medicine 12% of population, 30 million people Tylenol versus NSAIDs chiropractors versus surgery

Healthcare Informatics Users are Amateurs rather than Professionals packaged Interspace with inferred navigation Internet Health Monitors for individuals Generate the Personal Repositories interact with health status questionnaires builds a customized dynamic database Construct the Analysis Environment similarity matching to locate similar patients Evolve Community Interspace statistical clustering for lifestyle coaching

Bioinformatics Center Institute for Biological Information Systems develop new information systems deploy to study biological systems integrated analysis for biological information analysis environment for community repositories Interspace technologies support Communities Basic Science: Individual Genomes Clinical Practice: Individual Patients

IBIS new glory Institute for Biological Information Systems unique facility for all Michigan laboratories interactive systems training for all levels IBIS reborne Thoth, sacred ibis who hatched the world inventor of writing, keeper of divine archives inventor of arts & sciences, medicine & surgery First of the magicians, he was called the Elder: His disciples claimed access to the crypt where he kept his books of magic, so they undertook to decipher and learn “these formulas which commanded all the forces of nature and subdued the very gods themselves”.