Transcript Principles and Practice of Information Security and Confidentiality in

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/amia2007/
including citation lists and links
and this PowerPoint
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 MeSH
term “Medical Informatics”, “Telemedicine” &
descendents or main MeSH 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
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Rebecca Jerome
Andrew Balas
Marion Ball
Dominic Covvey
Robert Dolin
Sherrilynne Fuller
Terri Hannan
Brian Haynes
Bill Hersh
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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 5A'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
(5A’s: Assess, Advise, Assist-written, Assist-referral,
Arrange). Measured adherence to 5A’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 5A’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 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 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 Alcohol. 2007 JanFeb;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:S95-101. [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:S59-67. [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 F2F 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 8th grade reading level, 9th
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, 661-678
(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 using single
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 500K 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 < 10e-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 10e-5 to 10e-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. PLoS 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. PLoS 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. PLoS Biol 5(10): e254
• 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. PLoS Biol 5(10): e254
• Results
– Comparing Venter’s DNA to NCBI reference human
sequence shows 4.1 million variants: 3.2M SNPs, 53K block
substitutions, 292K heterozygous insert/delete events
(indels), 559K 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):i282-8.
[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):i282-8.
• 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 (25K genes
generate 400K 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 dbGAP 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 dbGAP 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 dbGAP 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 (>$50K)
3000000
2500000
2000000
1500000
1000000
500000
0
2002
2003
2004
2005
2006
2007 (YTD)
AMIA Visibility
Media Citations
1000
900
800
700
600
500
400
300
200
100
0
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
(YTD)
“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 dbGAP 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 dbGAP 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 dbGAP 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 dbGAP 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 dbGAP 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/amia2007/
including citation lists and links
and this PowerPoint