Biomedical Informatics Year in Review Daniel R. Masys, MD Professor and Chair Department of Biomedical Informatics Professor of Medicine Vanderbilt University School of Medicine
2007 Year in Review Content for this session is at: http: //dbmichair. mc. vanderbilt. edu/amia 2007/ including citation lists and links and this Power. Point
Design for this Session • Modeled on American College of Physician “Update” sessions • Emphasis on ‘what it is’ and ‘why it is important’ • 1 -2 examples of each in detail and others in synopsis • Audience interaction for each category of item discussed
Source of Content for Session • Literature review of RCTs indexed by Me. SH term “Medical Informatics”, “Telemedicine” & descendents or main Me. SH term “Bioinformatics”, and publication date between November 2006 and October 2007 (n=42), further qualified by involvement of >100 providers or patients • Poll of American College of Medical Informatics fellows list
It takes a village… Thanks to • • • Rebecca Jerome Andrew Balas Marion Ball Dominic Covvey Robert Dolin Sherrilynne Fuller Terri Hannan Brian Haynes Bill Hersh • • • Betsy Humphreys George Hripcsak Bonnie Kaplan Denis Protti Don Simborg David States Paul Tang Mark Tuttle William Yasnoff
Topics • Representative New Literature • Notable Events – the ‘Top Ten’ list
New Literature Highlights: Clinical Informatics • Unintended consequences of clinical information technology • Clinical Decision Support • Telemedicine • The practice of informatics
New Literature Highlights: Bioinformatics and Computational Biology • Human Health and Disease • The practice of bioinformatics
Unintended consequences of clinical information technology
Unintended Consequences of Information Technologies • Reference – Linder et al. , Arch Intern Med. 2007 Jul 9; 167(13): 1400 -5. [Brigham & Women’s Hospital] • Title – Electronic health record use and the quality of ambulatory care in the United States. • Aim – Assess effects of Electronic Health Records on quality of care delivered in ambulatory settings • Methods – Retrospective, cross-sectional analysis of 17 quality measures from 2003 -2004 National Ambulatory Medical Care Survey, correlated with use of EHRs.
Unintended Consequences of Information Technologies • Reference – Linder et al. , Arch Intern Med. 2007 Jul 9; 167(13): 1400 -5. • Results – EHRs used in 18% of 1. 8 billion visits – For 14 of 17 quality measures, fraction of visits where recommended best practice occurred was no different in EHR settings than manual records settings. – 2 better with EHR: avoiding benzodiazepines in depression, avoiding routine urinalysis – 1 worse with EHR: prescribing statins for hypercholesteremia (33% vs. 47%, p=0. 01) • Conclusion – As implemented, EHRs not associated with better quality ambulatory care
Unintended Consequences of Information Technologies • Reference – Linder et al. , Arch Intern Med. 2007 Jul 9; 167(13): 1400 -5. • Importance – Received disproportionate media attention due to reactionary message – Lost in the media hype: Less than 40% of EHR implementations have all elements important for effects on quality (e-prescribing, test ordering, results, clinical notes, decision support). – Best performance regardless of infrastructure was suboptimal (< 50% adherence to best practice).
Clinical Decision Support for Providers • Reference – Raebel MA et al. J Am Geriatr Soc. 2007 Jul; 55(7): 977 -85. [Kaiser Permanente, Denver, Colorado] • Title – Randomized trial to improve prescribing safety in ambulatory elderly patients. • Aim – To determine whether a computerized tool that alerted pharmacists when patients aged 65 and older were newly prescribed potentially inappropriate medications was effective in decreasing the proportion of patients dispensed these medications. • Methods – 60, 000 pts randomized evenly; in intervention group pharmacists got e-alerts for 11 types of medication
Clinical Decision Support for Providers • Reference – Raebel MA et al J Am Geriatr Soc. 2007 Jul; 55(7): 977 -85. • Results – Over 1 year, 543 (1. 8%) of intervention groups over age 65 were prescribed targeted meds, vs. 644 (2. 2%) of usual care group (P= 0. 002) – Statistically significant drop in use of amitryptiline and diazepam. • Importance – Adds to extensive literature on reducing Adverse Drug Effects via alerts and reminders – Targeting healthcare team members who can modify physician orders has beneficial effect – Note: Similar design study of meds during pregnancy reported in JAMIA July-Aug 2007
Clinical Decision Support for Providers • Reference – Bailey T et al. Arch Intern Med. 2007 Mar 26; 167(6): 586 -90. [Wash U. , St. Louis] • Title – An intervention to improve secondary prevention of coronary heart disease. • Aim – Determine whether alerts sent to pharmacists, combined with ‘academic detailing’ by pharamacists, change physician prescribing behavior. • Methods – RCT randomizing patients with acute MI in hospital setting to alerts sent to pharmacist based on elevated troponin I levels. Pharmacists receiving alerts reviewed inpt meds list and communicated with care providers.
Clinical Decision Support for Providers • Reference – Bailey T et al. Arch Intern Med. 2007 Mar 26; 167(6): 586 -90. • Methods, cont’d – Outcome measures: proportion of Pts discharged on ASA, beta-blockers, ACE inhibitors, and statins. • Results – Improved compliance with ACE and statin guidelines, no impact on beta blockers or ASA. – When all 4 classes of drugs considered together, 84% (305 of 365 eligible) intervention vs. 70% (343 of 488) in control received recommended therapy (P<0. 001) • Importance – Routing messages to pharmacists, combined with academic detailing, provides useful model for systematic improvements in care
Clinical Decision Support • Reference – Chaudhry R et al. Arch Intern Med. 2007 Mar 26; 167(6): 606 -11. [Mayo Clinic] • Title – Web-based proactive system to improve breast cancer screening: a randomized controlled trial. • Aim – Improve mammography screening rates using alerts and reminders directed at appointment secretaries. • Methods – Web-based preventive care reminder system created to alert staff making appointments about screening mammography. – 6600 patients signed up for study, randomized to usual care or use of system that sent a letter or e-mail message in advance of screening data, and provided response status to appt. secretary.
Clinical Decision Support • Reference – Chaudhry R et al. Arch Intern Med. 2007 Mar 26; 167(6): 606 -11. • Results – Screening rate for annual mammography was 64% in intervention group vs. 55% in control group (P<. 001) – No difference in intervention vs. control on any other preventive service. • Conclusion – Practice re-design to send reminder messages to appointment secretary rather than to physician provider improved compliance with preventive care services guidelines. • Importance – More evidence that care team members other than physicians are better targets for information interventions designed to increase consistency of care.
Clinical Decision Support for Providers • 3 RCTs on Tobacco Cessation – Unrod et al. Randomized controlled trial of a computerbased, tailored intervention to increase smoking cessation counseling by primary care physicians. J Gen Intern Med. 2007 Apr; 22(4): 478 -84. [Mt. Sinai, NYC] – Wadland WC et al Practice-based referrals to a tobacco cessation quit line: assessing the impact of comparative feedback vs general reminders. Ann Fam Med. 2007 Mar -Apr; 5(2): 135 -42. [Michigan State] – Bentz CJ et al. Provider feedback to improve 5 A's tobacco cessation in primary care: a cluster randomized clinical trial. Nicotine Tob Res. 2007 Mar; 9(3): 341 -9. [Providence/St. Vincent, Portland, OR]
Clinical Decision Support for Providers • Methods – Mt. Sinai study: Computer tailored one page summary to physician and patient re: Smoking Cessation Guidelines (5 A’s: Assess, Advise, Assist-written, Assist-referral, Arrange). Measured adherence to 5 A’s guidelines, and smoking cessation success at 6 months – MSU study: Provider specific feedback on smoking cessation referrals vs. general reminders. Measured referral numbers and quit rate at 18 months. – Providence Portland study: Provider specific monthly feedback reports vs. no feedback from state tobacco quitline.
Clinical Decision Support for Providers • Results – All three studies showed statistically improved compliance with 5 A’s guidelines by providers and increased in referrals for cessation help (Odds ratios 2. 7 – 5) – All showed increased numbers of patients quitting smoking at borderline statistical significance levels vs. control groups • Conclusion – Modest positive impacts of proactive (tailored information sheet) and retrospective (regular feedback reports on numbers of referrals) smoking cessation interventions – Interventions judged to be cost effective and are continuing • Importance – Approximately the same results in a CDSS area (smoking cessation) from three different sites with similar intervention and process/outcomes measures – Information intervention necessary but not sufficient to achieve optimal outcomes
Clinical Decision Support for Providers • Reference – Rothschild JM, et. al. Transfusion. 2007 Feb; 47(2): 228 -39. [Brigham and Women’s, Boston] • Title – Assessment of education and computerized decision support interventions for improving transfusion practice. • Aim – Reduce overuse of blood products via a CDSS intervention. • Methods – Random assignment of junior house officers to receiving education and CPOE-based decision support at time of ordering blood products. – Orders classified as DS-agree or DS-disagree – DS-disagree charts reviewed for appropriateness
Clinical Decision Support for Providers • Reference – Rothschild JM, et. al. Transfusion. 2007 Feb; 47(2): 228 -39. • Results – Inappropriate non-emergent transfusion at baseline was 72% in both interventional and control groups. – Improved to 63% with conventional education. – DS intervention group continued to improve to 59%. – Physicians accepted 14% of DS-recommended orders, especially recommendations to increase dose (73%). • Conclusion – Education and CDSS had statistically significant reduction of inappropriate transfusion orders, though residual amount remained high. • Impact – Don’t be sanguine about expecting CDSS to change prescribing
Clinical Decision Support for Providers • Reference – Kheterpal et al. Anesth Analg. 2007 Mar; 104(3): 592 -7. [Univ. Michigan] • Title – Electronic reminders improve procedure documentation compliance and professional fee reimbursement. • Aim – To evaluate alert system to improve documentation of care for increased reimbursement. • Methods – Automated system scanned EMR for surgical procedures using arterial catheters, sent e-mail and/or pager reminder to provider if no procedure note about catheter placement. – Residents and CRN anesthetists randomized to msg or no msg
Clinical Decision Support for Providers • Reference – Kheterpal et al. Anesth Analg. 2007 Mar; 104(3): 592 -7. • Results – Baseline compliance rate 80% – During 2 month study, 88% of intervention group completed documentation requirements vs. 75% of control. – After RCT ended, all staff got reminder and compliance rose to 98% – Professional fee reimbursement projected to increase $40, 500 over 12 months. • Conclusion – Documentation deficiencies amenable to alerts/reminders • Impact – ADSS works in a fashion similar to CDSS, perhaps better
Clinical Decision Support for Patients • Reference – Thompson RG et al. Qual Saf Health Care. 2007 Jun; 16(3): 216 -23. [Univ Newcastle, UK] • Title – A patient decision aid to support shared decision-making on anti-thrombotic treatment of patients with atrial fibrillation: randomised controlled trial. • Aim – To determine the efficacy of a computerised decision aid in patients with atrial fibrillation making decisions on whether to take warfarin or aspirin therapy. • Methods – 109 Pts with a. fib randomized to computerized DSS vs. pamphlet on ASA vs. warfarin – Outcomes: decision conflict scale, and therapy choice
Clinical Decision Support for Patients • Reference – Thompson RG et al. Qual Saf Health Care. 2007 Jun; 16(3): 216 -23. • Results – Decision conflict lower in CDSS group (ie. , happier with decision made) – CDSS Pts agreed to start coumadin only 25% of time when recommended by physician, vs. 94% of printed guidelines group • Conclusion – CDSS for patients can empower them to feel comfortable about decisions that are medically suboptimal • Impact – Increased understanding mediated by CDSS systems is a double edged sword
Clinical Decision Support for Patients • Reference – Saitz R et al. Alcohol. 2007 Jan-Feb; 42(1): 28 -36. [Boston Univ. ] • Title – Screening and brief intervention online for college students: the ihealth study. • Aim – To test the feasibility of online alcohol screening and brief intervention (BI) by comparing (i) two approaches to inviting all students to be screened, and (ii) a minimal versus a more extensive BI. • Methods – All freshman students(4008) sent one of two e-mail invitations to participate in alcohol counseling online application: either invitation for general health assessment, or invitation for alcohol assessment
Clinical Decision Support for Patients • Reference – Saitz R et al. Alcohol. 2007 Jan-Feb; 42(1): 28 -36 • Methods, cont’d – Participants with unhealthy alcohol use randomly assigned to minimal or more extensive information intervention – Follow-up after one month for those receiving interventions • Results – 55% of students completed online screening, no difference if invitation specifically mentioned alcohol vs. general health. – 37% of male students and 26% of female students had unhealthy alcohol use. – More extensive intervention caused more students to expression interest in changing behavior – 75% of intervention completed second assessment, and of these unhealthy behaviors reduced by 33% in women and 15% in men.
Clinical Decision Support for Patients • Reference – Saitz R et al. Alcohol. 2007 Jan. Feb; 42(1): 28 -36 • Conclusion – Over half of freshman class reached by e-mail and completed health risk assessment – Mention of alcohol not a deterrent to participation – Brief online intervention appeared to have favorable short term impact. • Impact – Contibutes to literature on self-reporting of health conditions traditionally considered ‘stigmatizing’
Clinical Decision Support for Patients • 2 RCTs on Smoking Cessation – Strecher VJ et al. Moderators and mediators of a web-based computer-tailored smoking cessation program among nicotine patch users. Nicotine Tob Res. 2006 Dec; 8 Suppl 1: S 95 -101. [Univ. Michigan] – Japuntich et al. Smoking cessation via the internet: a randomized clinical trial of an internet intervention as adjuvant treatment in a smoking cessation intervention. Nicotine Tob Res. 2006 Dec; 8 Suppl 1: S 59 -67. [Univ Wisconsin Madison]
Clinical Decision Support for Patients • Methods – Michigan study: 3971 smokers who purchased nicotine patches randomized to standard webbased materials vs. tailored web intervention. Measured abstinence at 12 weeks. – Wisconsin study: 284 smokers randomized to bupropion + counseling +/- access to an online support group and information site. Measured abstinence at 12 weeks and 24 weeks.
Clinical Decision Support for Patients • Results – Michigan study found tailored program more effective by number abstinent in certain subgroups (children at home, frequent alcohol use, tobacco-related illness present) but not significant for groups as whole – Wisconsin study found use of online resources correlated with smoking abstinence, but no overall difference in abstinence between groups. • Conclusion – Targeted information interventions help a subset of smokers to quit who would not otherwise • Importance – Addiction interventions are a difficult area of therapeutics, for which informatics has a modest role to play
New CDSS RCTs showing no difference for intervention vs. control 1. Curtis et al. Challenges in improving the quality of osteoporosis care for long-term glucocorticoid users: a prospective randomized trial. Arch Intern Med. 2007 Mar 26; 167(6): 591 -6. 2. Glassman et al. The utility of adding retrospective medication profiling to computerized provider order entry in an ambulatory care population. J Am Med Inform Assoc. 2007 Jul -Aug; 14(4): 424 -31. 3. Schapira et al. Decision-making at menopause: a randomized controlled trial of a computer-based hormone therapy decision -aid. Patient Educ Couns. 2007 Jul; 67(1 -2): 100 -7. 4. Tuil et al. Empowering patients undergoing in vitro fertilization by providing Internet access to medical data. Fertil Steril. 2007 Aug; 88(2): 361 -8.
Clinical Decision Support Questions and Comments
Telemedicine 12 new RCTs published November 2006 – October 2007 • 3 chronic airways disease • 2 psychiatric care • 2 diabetes care • 2 imaging: dermatology and ophthalmology • 1 each prostate cancer, cardiac rehab, hypertension
Telemedicine • 3 RCTs on airways disease – Chan DS et al. Internet-based home monitoring and education of children with asthma is comparable to ideal office-based care: results of a 1 -year asthma in-home monitoring trial. Pediatrics. 2007 Mar; 119(3): 569 -78. [Tripler Army Medical Center, Honolulu] – Jan RL et al. An internet-based interactive telemonitoring system for improving childhood asthma outcomes in Taiwan. Telemed J E Health. 2007 Jun; 13(3): 257 -68. [National Cheng Kung University, Taiwan] – Whitten P, Mickus M. Home telecare for COPD/CHF patients: outcomes and perceptions. J Telemed Telecare. 2007; 13(2): 69 -73. [Michigan State University]
• Methods Telemedicine – Tripler study: 120 asthma pts age 6 -17 randomized to same clinical pathway with follow-up either via office visit or website interaction. Measured medication adherence, PFTs – Taiwan study: 88 asthma pts randomized to either Internet care guidance and spirometry reporting, or printed materials and spirometry diary. Measured self-reported symptoms, spirometry results, quality of life, knowledge of disease – Michigan State study: 161 pts with COPD/CHF randomized to home care visits in person or via telemedicine unit. Measured SF-36, patient perceptions, physiologic status at beginning and end of study.
Telemedicine • Results – Taiwanese study found telemedicine group had better adherence to meds, better PFTs. – Other two studies found clinical equivalence of telemedicine and face-toface visits at home or office • Impact – Adds to substantial literature showing therapeutic equivalency of telemedicine vs. in person monitoring of chronic airways disease.
Telepsychiatry • 2 RCTs – Fortney JC et al. A randomized trial of telemedicinebased collaborative care for depression. J Gen Intern Med. 2007 Aug; 22(8): 1086 -93. Epub 2007 May 10. [VA Health Svcs Research, Little Rock AR] – O'Reilly R. Is telepsychiatry equivalent to face-toface psychiatry? Results from a randomized controlled equivalence trial. Psychiatr Serv. 2007 Jun; 58(6): 836 -43. [Regional Mental Healthcare, London, Ontario, Canada]
Telepsychiatry • Methods – VA study: 395 pts with moderately severe depression followed at small VA community clinics without psychiatrists. Measured med adherence, treatment response, quality of life, pt satisfaction with treatment. – Canadian study: 495 pts referred for initial psych consultation randomized to telepsych interview or face-to-face consult. Measured health status, patient satisfaction, costs
Telepsychiatry • Results – VA study: supplementing usual care with telemedicine psych consultation improved medication adherence and therapeutic response. Also found higher patient satisfaction, and better quality of life measures in intervention group. – Canadian study found equivalence for telepsychiatry outcomes and face to face outcomes, with 10% decrease in overall costs for telemedicine based care. • Impact – Telemedicine technologies can extend subspecialty support to primary care settings – Telepsychiatry equivalent to F 2 F as perceived by Pts
Tele-imaging • 2 RCTs – Conlin PR et al. Nonmydriatic teleretinal imaging improves adherence to annual eye examinations in patients with diabetes. J Rehabil Res Dev. 2006 Sep -Oct; 43(6): 733 -40. [Boston VA] – Pak H, et al. Store-and-forward teledermatology results in similar clinical outcomes to conventional clinic-based care. J Telemed Telecare. 2007; 13(1): 26 -30. [Army TATRC, Fort Dietrick MD]
Tele-imaging • Methods – VA study: 448 pts randomized to annual dilated eye exam vs. non-dilated screening image with remote interpretation, followed by in person consult if indicated. Measured correspondence of remote and in person findings, and adherence to annual exam schedule – Army study: 776 pts randomized to face-toface dermatology consult vs. telemedicine via store and forward imaging + text description
Tele-imaging • Results – VA study: Strong but not perfect correlation of tele-imaging with dilated in person exam. Improvement in compliance with annual screening. Patient acceptance high. – Army study found equivalence of diagnosis and ongoing monitoring of response to therapy for teledermatology and in person care. • Impact – Store and forward telemedicine lends itself well to specialties where static images are keys to diagnosis and follow-up
2006 -7 Telemedicine RCTs • Continue 30+ year history of showing equivalence of telemedicine for selected types of home monitoring, chronic disease follow-up, and visual diagnosis • Only 1 of 12 addressed cost vs. benefit • Leave unaddressed principal historical impediments to telemedicine acceptance: reimbursement, licensure, liability
Telemedicine Questions and Comments
Practice of Informatics • Reference – Beebe TJ et al. Health Serv Res. 2007 Jun; 42(3 Pt 1): 1219 -34. [Mayo Clinic] • Title – Mixing web and mail methods in a survey of physicians. • Aim – To assess the effects of two different mixed-mode (mail and web survey) combinations on response rates, response times, and nonresponse bias in a sample of primary care and specialty internal medicine physicians. • Methods – Randomized 500 physicians at Mayo clinic to receiving either a mailed paper survey on EMR, or web link for online survey, with cross over.
Practice of Informatics • Reference – Beebe TJ et al. Health Serv Res. 2007 Jun; 42(3 Pt 1): 1219 -34. • Results – Overall response rate higher with mailed survey sent first than web link sent first (70% vs. 63%). – Results obtained 2 days faster with web survey – Key outcome variables no different in paper vs. web survey methods • Impact – Some insight on approaches to surveying physicians in large institutional setting
Practice of Informatics • Reference – Tideman R et al. Sex Transm Infect. 2007 Feb; 83(1): 526. [Univ. of Melbourne, Australia] • Title – A randomised controlled trial comparing computerassisted with face-to-face sexual history taking in a clinical setting. • Aim – To compare computer-assisted self-interview (CASI) with routine face-to-face interview (FTFI) for sexual history taking from patients in a clinical setting. • Methods – Randomized 713 new walk-in patients at STD clinic to CASI or FTFI initial assessment. CASI subsequently had FTFI.
Practice of Informatics • Reference – Tideman R et al. Sex Transm Infect. 2007 Feb; 83(1): 52 -6. • Methods, cont’d – Comparison of self-reported risk behaviors, concordance of CASI and FTFI assessments. • Results – 85% of CASI pts comfortable with method – Results equivalent except that women using CASI reported more male partners than in FTFI setting, and CASI users reported Hep B vaccination more often. • Conclusion – CASI efficient and acceptable method for gathering sexual risk data in STD clinic setting
Practice of Informatics • Reference – Bates B, et al. J Cancer Educ. 2007 Spring; 22(1): 15 -20. [Ohio Univ. ] • Title – The effect of improved readability scores on consumers' perceptions of the quality of health information on the internet. • Methods – 519 community participants randomized to receive lung cancer prevention level at 8 th grade reading level, 9 th grade, or first year college reading level. – Measured perceived trustworthiness, readability, completeness.
Practice of Informatics • Reference – Bates B, et al. J Cancer Educ. 2007 Spring; 22(1): 15 -20. • Results – Reducing reading level had no significant effect on perceived readability, trustworthiness, or completeness. • Conclusion – Conventional wisdom about relationship of readability and effectiveness not supported in this study • Importance – Of potential relevance to IRBs and guidelines for informed consent documentation
Practice of Informatics • Reference – Schneider S. et al. Oncol Nurs Forum. 2007 Jan; 34(1): 39 -46. [Duke Univ. ] • Title – Virtual reality: a distraction intervention for chemotherapy. • Aim – To explore virtual reality (VR) as a distraction intervention to relieve symptom distress in adults receiving chemotherapy treatments for breast, colon, and lung cancer. • Methods – 123 patients in cross-over design, serving as own control. Received Virtual Reality headset as distraction during chemotherapy at one visit, and not the next.
Practice of Informatics • Reference – Schneider S. et al. Oncol Nurs Forum. 2007 Jan; 34(1): 39 -46. . • Methods, cont’d – Measured symptom distress, fatigue, anxiety, open ended questionnaire regarding experience. • Results – Using VR made chemotherapy treatment seem shorter and pts liked VR treatment sessions better than std. – However, no difference in symptom distress immediately or at 2 days post treatment
Practice of Informatics • Reference – Schneider S. et al. Oncol Nurs Forum. 2007 Jan; 34(1): 39 -46. . • Conclusions – VR distraction can make chemotherapy treatments more palatable but do not decrease therapyassociated symptoms • Impact – Pharmacology trumps perceptual psychology in chemotherapy settings
Practice of Informatics Questions and Comments
New Literature Highlights: Bioinformatics and Computational Biology • Human Health and Disease • The practice of bioinformatics
Bioinformatics: Human Health & Disease • Reference – The Wellcome Trust Case Control Consortium. Nature 447, 661678 (7 June 2007) • Title – Genome-wide association study of 14, 000 cases of seven common diseases and 3, 000 shared controls. • Aim – To find genetic determinants of 7 major diseases usingle nucleotide polymorphism (SNP) assessments at 500, 000 loci, in 14, 000 patients • Methods – 54 centers in UK enrolled 14, 000 volunteers, whose DNA was genotyped with Affymetrix 500 K SNP chip. – Case control study design
Bioinformatics: Human Health & Disease • Reference – The Wellcome Trust Case Control Consortium. Nature 447, 661 -678 (7 June 2007) • Results – 24 association signals significant at P < 10 e-7 – 1 in bipolar disorder, 1 in coronary disease, 9 in Crohn’s disease, 3 in Rheumatoid arthritis, 7 in type I diabetes, 3 in type 2 diabetes – 58 other SNP polymorphisms with differences at 10 e-5 to 10 e-7 • Importance – The era of genome-wide scans has arrived. – Personalized medicine based on individual SNPs and linked SNP patterns (ie. , haplotypes) will significantly inform personalized disease prevention, diagnosis and treatment – Level of complexity will make decision support rules and CDSS essential
Bioinformatics: Human Health & Disease • Reference – Estivill et al. PLo. S Genet. 2007 Oct 19; 3(10): 1787 -99. • Title – Copy number variants and common disorders: filling the gaps and exploring complexity in genome-wide association studies. • Aim – Discussion of contribution of gene Copy Number Variation (CNV) to human disorders. • Methods – Literature review of GWAS studies and contribution of CNV to explaining genetic diversity
Bioinformatics: Human Health & Disease • Reference – Estivill et al. PLo. S Genet. 2007 Oct 19; 3(10): 1787 -99. • Results – Reduplicated genes account for some of the unexplained variation seen in genome-association studies. – CNV’s not detected by standard SNP technologies, but have been shown to contribute to genetic variance in Parkinson’s disease, Alzheimer, Autism, retardation, and chronic pancreatitis • Importance – Copy Number Variation is an important new genetic concept that will have relevance in explaining complex traits and some diseases
Bioinformatics: Human Health & Disease • Reference – Levy et al. PLo. S Biol 5(10): e 254 • Title – The Diploid Genome Sequence of an Individual Human. • Aim – Full genome sequence of J. Craig Venter, compared to consensus published human genome sequence • Methods – Standard DNA sequencing technologies applied to single individual rather than small group of reference samples
Bioinformatics: Human Health & Disease • Reference – Levy et al. PLo. S Biol 5(10): e 254 • Results – Comparing Venter’s DNA to NCBI reference human sequence shows 4. 1 million variants: 3. 2 M SNPs, 53 K block substitutions, 292 K heterozygous insert/delete events (indels), 559 K homozygous indels – Non-SNP variability accounts for 74% of variant bases. – 44% of all genes heterozygous for 1 or more variants • Importance – Inter-individual variations may be 3 -4 fold higher than previously estimated (99. 5% vs. 99. 9%)
The Practice of Bioinformatics • Reference – Duarte N et al. Proc Natl Acad Sci U S A. 2007 Feb 6; 104(6): 1777 -82. [UC San Diego] • Title – Global reconstruction of the human metabolic network based on genomic and bibliomic data. • Aim – Develop a computationally tractable, complete map of human metabolism • Methods – Combine genome annotations of complete human genome with 50 years of published literature (bibliome) on human metabolic pathways.
Bioinformatics: Practice of Bioinformatics • Reference – Duarte N et al. Proc Natl Acad Sci U S A. 2007 Feb 6; 104(6): 177782. • Results – Systems biology project to create in silico model of all metabolic pathways in humans, and their genetic determinants – Mathematical network analysis of resulting relationships show biological insights about intracellular compartmentalization (e. g. , drug accessibility) and many gaps in understanding of relationships among metabolic pathways • Importance – An example of new systems biology tools that combine mathematical analysis techniques with knowledge derived from the published literature – Traditional intermediary metabolism pathways (e. g. , Sigma chart of cell) have many unexplained gaps
The Practice of Bioinformatics • Reference – Lim WK et al. Bioinformatics. 2007 Jul 1; 23(13): i 282 -8. [Columbia Univ. ] • Title – Comparative analysis of microarray normalization procedures: effects on reverse engineering gene networks. • Aim – Develop a more appropriate method for normalizing gene expression data for reconstructing gene networks • Methods – Comparison of commonly used algorithms for rendering data from different Affymetrix genechip experiments comparable
Bioinformatics: Practice of Bioinformatics • Reference – Lim WK et al. Bioinformatics. 2007 Jul 1; 23(13): i 282 -8. • Results – Genechips designed for pairwise comparison of gene expression values. Inferring complex network relationships is an ‘off-label use’ that can be affected by methodologic errors of normalization – A better normalization algorithm developed at Columbia’s DBMI is presented • Importance – Mathematics of high dimensionality data from genechips is complex – Systems biology requires careful attention to making data from multiple experiments comparable
The Practice of Bioinformatics • Reference – Bandeira et al. Proc Natl Acad Sci U S A. 2007 Apr 10; 104(15): 6140 -5. [UC San Diego] • Title – Protein identification by spectral networks analysis. • Aim – Develop a better method for interpretation of mass spectroscopy signals for proteomics • Methods – Use modified & unmodified versions of the same peptide to improve speed and efficiency of protein identification
Bioinformatics: Practice of Bioinformatics • Reference – Bandeira et al. Proc Natl Acad Sci U S A. 2007 Apr 10; 104(15): 6140 -5. • Results – Converts protein identification from exhaustive database searching problem to fast pattern matching problem • Importance – Proteomics is more complex than genomics (25 K genes generate 400 K proteins) and computationally challenging – Representative of novel algorithms to rapidly identify proteins affected by post-translational modification
Computational Biology and Bioinformatics Questions and Comments
Top Ten List of Notable Events in the Past 12 months
“Top Ten” Events #10 – Legislation mandates reporting of results in Clinicaltrials. gov 12/2006
“Top Ten” Events #10 – Legislation mandates reporting of results in Clinicaltrials. gov 12/2006 #9 – Public access to genome-phenome correlation data begins 10/1/2007 – NCBI db. GAP database online
“Top Ten” Events #10 – Legislation mandates reporting of results in Clinicaltrials. gov 12/2006 #9 – Public access to genome-phenome correlation data begins 10/1/2007 – NCBI db. GAP database online #8 – Patient Safety Institute founded in 2001 in response to IOM “To Error is Human” report fails
#7 – International Terminology Standards Development Organization Formed April 26, 2007
“Top Ten” Events #10 – Legislation mandates reporting of results in Clinicaltrials. gov 12/2006 #9 – Public access to genome-phenome correlation data begins 10/1/2007 – NCBI db. GAP database online #8 – Patient Safety Institute founded in 2001 in response to IOM “To Error is Human” report fails #7 – International Terminology Standards Development Organization Formed #6 – AMIA clout and visibility increases
AMIA R&D funding growth Grants and Contracts (>$50 K)
AMIA Visibility Media Citations
“Top Ten” Events #10 – Legislation mandates reporting of results in Clinicaltrials. gov 12/2006 #9 – Public access to genome-phenome correlation data begins 10/1/2007 – NCBI db. GAP database online #8 – Patient Safety Institute founded in 2001 in response to IOM “To Error is Human” report fails #7 – International Terminology Standards Development Organization Formed #6 – AMIA clout and visibility increases #5 – NIH redefines scope of CTSA program
“Top Ten” Events #10 – Legislation mandates reporting of results in Clinicaltrials. gov 12/2006 #9 – Public access to genome-phenome correlation data begins 10/1/2007 – NCBI db. GAP database online #8 – Patient Safety Institute founded in 2001 in response to IOM “To Error is Human” report fails #7 – International Terminology Standards Development Organization Formed #6 – AMIA clout and visibility increases #5 – NIH redefines scope of CTSA program #4 – Publication of J. Craig Venter’s DNA sequence
“Top Ten” Events #10 – Legislation mandates reporting of results in Clinicaltrials. gov 12/2006 #9 – Public access to genome-phenome correlation data begins 10/1/2007 – NCBI db. GAP database online #8 – Patient Safety Institute founded in 2001 in response to IOM “To Error is Human” report fails #7 – International Terminology Standards Development Organization Formed #6 – AMIA clout and visibility increases #5 – NIH redefines scope of CTSA program #4 – Publication of J. Craig Venter’s DNA sequence #3 – ONC begins plan to transition AHIC to private sector
“Top Ten” Events #10 – Legislation mandates reporting of results in Clinicaltrials. gov 12/2006 #9 – Public access to genome-phenome correlation data begins 10/1/2007 – NCBI db. GAP database online #8 – Patient Safety Institute founded in 2001 in response to IOM “To Error is Human” report fails #7 – International Terminology Standards Development Organization Formed #6 – AMIA clout and visibility increases #5 – NIH redefines scope of CTSA program #4 – Publication of J. Craig Venter’s DNA sequence #3 – ONC begins plan to transition AHIC to private sector #2 – Microsoft and Google announce plans for Personal Health Records
And the #1 top event of 2007 is…
“Top Ten” Events #10 – Legislation mandates reporting of results in Clinicaltrials. gov 12/2006 #9 – Public access to genome-phenome correlation data begins 10/1/2007 – NCBI db. GAP database online #8 – Patient Safety Institute founded in 2001 in response to IOM “To Error is Human” report fails #7 – International Terminology Standards Development Organization Formed #6 – AMIA clout and visibility increases #5 – NIH redefines scope of CTSA program #4 – Publication of J. Craig Venter’s DNA sequence #3 – ONC begins plan to transition AHIC to private sector #2 – Microsoft and Google announce plans for Personal Health Records #1 – CMS begins program to reward small practices for using EHRs
The Year in Review Summary… We is confronted by an insurmountable tidal wave of opportunity Pogo
Content for this session is at: http: //dbmichair. mc. vanderbilt. edu/amia 2007/ including citation lists and links and this Power. Point
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