Title

以網路服務為基礎的新生兒代謝疾病篩檢系統

Translated Titles

A Web-Service-Based Newborn Screening System for Metabolic Diseases

DOI

10.6342/NTU.2013.00468

Authors

陳偉昕

Key Words

網路服務 ; 新生兒篩檢 ; 串聯質譜儀 ; 醫療資訊系統 ; 新生兒代謝疾病 ; 資料探勘 ; Web-Based Services ; Newborn Screening ; Tandem Mass Spectrometry ; Hospital Information Systems ; Inborn Errors of Metabolism ; Data Mining

PublicationName

臺灣大學生醫電子與資訊學研究所學位論文

Volume or Term/Year and Month of Publication

2013年

Academic Degree Category

博士

Advisor

賴飛羆

Content Language

英文

Chinese Abstract

新生兒篩檢是在早期判斷出新生兒代謝疾病的方法,透過新生兒的採血,由血液樣本進行串聯質譜儀的分析,可以及早防治與給予治療。為此我們在台大醫院開發了一套新生兒篩檢資料處理系統,這個系統包含了樣本收集、檢驗資料上傳分析、給予治療與追蹤病人的功能。在本研究中,我們使用了資料探勘的方法來提高新生兒代謝疾病的辨識率,首先,我們將2002年到2007年七月的紙本新生兒篩檢室的資料數位化,並且把所有新生兒的篩檢資料彙集成資料庫。在本研究中,我們的機器學習方法將應用於苯酮尿症、高甲硫胺酸血症與3-甲基巴豆醯輔酵素羧化酵素缺乏症,藉由嘗試新的特徵組合配合最佳特徵抽取的方法,我們得到了對不同的疾病的最佳模型,可以大幅的下降偽陽性的個案,並且可以正確的判斷出所有陽性的病人。由此可知,此系統可以準確的判斷新生兒篩檢相關疾病,並且可以更有效的利用醫療資源。

English Abstract

A Hospital Information System that integrates screening data and interpretation of the data is routinely requested. However, the accuracy of disease classification may be low because of the disease characteristics and analytes used for classification. The objective of this study is to describe a system that enhanced the neonatal screening system of the Newborn Screening Center at the National Taiwan University Hospital. The system has been designed and deployed based on a Service-Oriented Architecture framework under the Web Services .NET environment. The system consists of sample collection, testing, diagnosis, evaluation, treatment and follow-up services among collaborating hospitals. To improve the accuracy of newborn screening, machine learning and optimal feature selection mechanisms were investigated for screening newborns for inborn errors of metabolism. In this study, machine learning classification was used to predict the following: phenylketonuria, hypermethioninemia, and 3-methylcrotonyl-CoA-carboxylase deficiency. The classification methods used 435,682 newborn samples collected at the Center between 2006 and 2012. These samples include 229 newborns with values over the diagnostic cutoffs and 1822 over the screening cutoffs but that do not meet the diagnostic cutoffs. The feature selection strategies were defined as follows. The original 35 analytes and the manifested features are ranked based on the F-score. Next, the combinations of the top 20 ranked features were selected as input features to Support Vector Machines classifiers to obtain optimal feature sets. Finally, the feature sets were tested using 5-fold cross validation and the optimal models were generated. The datasets collected in year 2011 and 2012 were utilized as the predicting cases. By adopting the results of this study, the number of suspected cases could be reduced dramatically. Furthermore, the results of the research have been compared with those of other methodologies.

Topic Category 基礎與應用科學 > 資訊科學
醫藥衛生 > 醫藥總論
電機資訊學院 > 生醫電子與資訊學研究所
Reference
  1. 3. Bodamer OA, Hoffmann GF, Lindner M. Expanded newborn screening in Europe 2007. Journal of inherited metabolic disease. 2007 Aug;30(4):439-44. PMID:17643197.
    連結:
  2. 6. Therrell Jr BL. U.S. Newborn Screening Policy Dilemmas for the Twenty-First Century. Molecular genetics and metabolism. 2001;74(1–2):64-74.
    連結:
  3. 7. Huang H-P, Chu K-L, Chien Y-H, Wei M-L, Wu S-T, Wang S-F, Hwu W-L. Tandem Mass Neonatal Screening in Taiwan—Report from One Center. Journal of the Formosan Medical Association. 2006;105(11):882-6.
    連結:
  4. 8. CSHN Department of Health. Expanded Newborn Screening using Tandem Mass Spectrometry Financial, Ethical, Legal and Social Issues (FELSI). 2012; Archived at: http://www.newbornscreening.info/, http://www.webcitation.org/6CSLRrSY5.
    連結:
  5. 9. Millington DS, Stevens RD. Acylcarnitines: analysis in plasma and whole blood using tandem mass spectrometry. Methods in molecular biology. 2011;708:55-72. PMID:21207283.
    連結:
  6. 10. Millington DS. Rapid and effective screening for lysosomal storage disease: how close are we? Clinical chemistry. 2008 Oct;54(10):1592-4. PMID:18824571.
    連結:
  7. 11. Vilarinho L, Rocha H, Sousa C, Marcao A, Fonseca H, Bogas M, Osorio RV. Four years of expanded newborn screening in Portugal with tandem mass spectrometry. Journal of inherited metabolic disease. 2010 Feb 23. PMID:20177789.
    連結:
  8. 12. Department of Health Victoria Australia. Genetic Services in Victoria. 2012; Archived at: http://www.health.vic.gov.au/genetics/strategy.htm, http://www.webcitation.org/6CUe929WH.
    連結:
  9. 13. Loukas YL, Soumelas GS, Dotsikas Y, Georgiou V, Molou E, Thodi G, Boutsini M, Biti S, Papadopoulos K. Expanded newborn screening in Greece: 30 months of experience. Journal of inherited metabolic disease. 2010 Aug 19. PMID:20721692.
    連結:
  10. 15. Watson MS, Mann MY, Lloyd-Puryear MA, Rinaldo P, Howell RR, American College of Medical Genetics Newborn Screening Expert G. Newborn Screening: Toward a Uniform Screening Panel and System—Executive Summary. Pediatrics. 2006;117(Supplement 3):S296-S307.
    連結:
  11. 16. Lindner M, Gramer G, Haege G, Fang-Hoffmann J, Schwab K, Tacke U, Trefz F, Mengel E, Wendel U, Leichsenring M, Burgard P, Hoffmann G. Efficacy and outcome of expanded newborn screening for metabolic diseases - Report of 10 years from South-West Germany *. Orphanet J Rare Dis. 2011 2011/06/20;6(1):1-10.
    連結:
  12. 17. Niu D-M, Chien Y-H, Chiang C-C, Ho H-C, Hwu W-L, Kao S-M, Chiang S-H, Kao C-H, Liu T-T, Chiang H, Hsiao K-J. Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan. Journal of inherited metabolic disease. 2010 2010/10/01;33(2):295-305.
    連結:
  13. 20. Rocha JC, Martins MJ. Oxidative stress in phenylketonuria: future directions. Journal of inherited metabolic disease. 2012 May;35(3):381-98. PMID:22116469.
    連結:
  14. 21. Bjursell MK, Blom HJ, Cayuela JA, Engvall ML, Lesko N, Balasubramaniam S, Brandberg G, Halldin M, Falkenberg M, Jakobs C, Smith D, Struys E, von Dobeln U, Gustafsson CM, Lundeberg J, Wedell A. Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function. American journal of human genetics. 2011 Oct 7;89(4):507-15. PMID:21963049.
    連結:
  15. 22. Naughten ER, Yap S, Mayne PD. Newborn screening for homocystinuria: Irish and world experience. European journal of pediatrics. 1998 Apr;157 Suppl 2:S84-7. PMID:9587032.
    連結:
  16. 23. Baumgartner M. 3-Methylcrotonyl-CoA carboxylase deficiency. 2003; Archived at: https://www.orpha.net/data/patho/GB/uk-MCC.html, http://www.webcitation.org/6CbdJ2ClE.
    連結:
  17. 26. Rosen P, Spalding SJ, Hannon MJ, Boudreau RM, Kwoh CK. Parent satisfaction with the electronic medical record in an academic pediatric rheumatology practice. Journal of medical Internet research. 2011;13(2):e40. PMID:21622292.
    連結:
  18. 30. Yoon D, Chang BC, Kang SW, Bae H, Park RW. Adoption of electronic health records in Korean tertiary teaching and general hospitals. International journal of medical informatics. 2012 Mar;81(3):196-203. PMID:22206619.
    連結:
  19. 31. Avidan A, Weissman C. Record completeness and data concordance in an anesthesia information management system using context-sensitive mandatory data-entry fields. International journal of medical informatics. 2012 Mar;81(3):173-81. PMID:22244818.
    連結:
  20. 32. Ohkubo S, Shimozawa K, Matsumoto M, Kitagawa T. Analysis of blood spot 17 alpha-hydroxyprogesterone concentration in premature infants--proposal for cut-off limits in screening for congenital adrenal hyperplasia. Acta paediatrica Japonica; Overseas edition. 1992 Apr;34(2):126-33. PMID:1621517.
    連結:
  21. 33. Lott JA, Sardovia-Iyer M, Speakman KS, Lee KK. Age-dependent cutoff values in screening newborns for hypothyroidism. Clinical biochemistry. 2004 Sep;37(9):791-7. PMID:15329318.
    連結:
  22. 34. Lindner M, Ho S, Fang-Hoffmann J, Hoffmann GF, Kolker S. Neonatal screening for glutaric aciduria type I: Strategies to proceed. Journal of inherited metabolic disease. 2006 2006/04/01;29(2-3):378-82.
    連結:
  23. 35. Matern D, Tortorelli S, Oglesbee D, Gavrilov D, Rinaldo P. Reduction of the false-positive rate in newborn screening by implementation of MS/MS-based second-tier tests: the Mayo Clinic experience (2004-2007). Journal of inherited metabolic disease. 2007 Aug;30(4):585-92. PMID:17643193.
    連結:
  24. 36. Turgeon CT, Magera MJ, Cuthbert CD, Loken PR, Gavrilov DK, Tortorelli S, Raymond KM, Oglesbee D, Rinaldo P, Matern D. Determination of total homocysteine, methylmalonic acid, and 2-methylcitric acid in dried blood spots by tandem mass spectrometry. Clinical chemistry. 2010 Nov;56(11):1686-95. PMID:20807894.
    連結:
  25. 37. Shigematsu Y, Hata I, Tajima G. Useful second-tier tests in expanded newborn screening of isovaleric acidemia and methylmalonic aciduria. Journal of inherited metabolic disease. 2010 Oct;33(Suppl 2):S283-8. PMID:20440648.
    連結:
  26. 38. Wang LY, Chen NI, Chen PW, Chiang SC, Hwu WL, Lee NC, Chien YH. Newborn screening for citrin deficiency and carnitine uptake defect using second-tier molecular tests. BMC medical genetics. 2013;14:24. PMID:23394329.
    連結:
  27. 41. Teodoro D, Pasche E, Gobeill J, Emonet S, Ruch P, Lovis C. Building a Transnational Biosurveillance Network Using Semantic Web Technologies: Requirements, Design, and Preliminary Evaluation. Journal of medical Internet research. 2012;14(3):e73. PMID:22642960.
    連結:
  28. 43. Yang TH, Cheng PH, Yang CH, Lai F, Chen CL, Lee HH, Hsu KP, Chen CH, Tan CT, Sun YS, editors. A Scalable Multi-tier Architecture for the National Taiwan University Hospital Information System based on HL7 Standard. Computer-Based Medical Systems, 2006 CBMS 2006 19th IEEE International Symposium on; 2006 0-0 0.10.1109/cbms.2006.27.
    連結:
  29. 44. Phan C, editor Service Oriented Architecture (SOA) - Security Challenges and Mitigation Strategies. Military Communications Conference, 2007 MILCOM 2007 IEEE; 2007 29-31 Oct. 2007.10.1109/milcom.2007.4455012.
    連結:
  30. 45. Cheng PH, Yang TH, Chen HS, Hsu KP, Chen SJ, Lai JS, editors. Codesign of a healthcare enterprise information portal and hospital information systems. Enterprise networking and Computing in Healthcare Industry, 2005 HEALTHCOM 2005 Proceedings of 7th International Workshop on; 2005 23-25 June 2005.10.1109/health.2005.1500501.
    連結:
  31. 50. Akay MF. Support vector machines combined with feature selection for breast cancer diagnosis. Expert Systems with Applications. 2009;36(2, Part 2):3240-7.
    連結:
  32. 51. Chen W-H, Chen H-P, Tseng Y-J, Hsu K-P, Hsieh S-L, Chien Y-H, Hwu W-L, Lai F, editors. Newborn Screening for Phenylketonuria: Machine Learning vs Clinicians. The 2012 IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining; 2012 Aug 2012; Istanbul, Turkey.
    連結:
  33. 1. Bartoshesky LE. Newborn Screening Tests. 2009; Archived at: http://kidshealth.org/parent/system/medical/newborn_screening_tests.html, http://www.webcitation.org/6CSJYu9CY.
  34. 2. The Children's Hospital at Westmead. The NSW Newborn Screening Programme. 2012; Archived at: http://www.chw.edu.au/prof/services/newborn/, http://www.webcitation.org/6CSKC26Tn.
  35. 4. Greene A. Newborn Screening Tests. 1996; Archived at: http://www.drgreene.com/qa/newborn-screening-tests, http://www.webcitation.org/6CUdYdzg4.
  36. 5. Lee KG. Newborn screening tests. 2011; Archived at: http://www.nlm.nih.gov/medlineplus/ency/article/007257.htm, http://www.webcitation.org/6CUdMnnsX.
  37. 14. Padilla CD, Therrell BL, Jr., Working Group of the Asia Pacific Society for Human Genetics on Consolidating Newborn Screening Efforts in the Asia Pacific R. Consolidating newborn screening efforts in the Asia Pacific region : Networking and shared education. Journal of community genetics. 2012 Jan;3(1):35-45. PMID:22271560.
  38. 19. Blau N, van Spronsen FJ, Levy HL. Phenylketonuria. Lancet. 2010 Oct 23;376(9750):1417-27. PMID:20971365.
  39. 24. Reference GH. 3-methylcrotonyl-CoA carboxylase deficiency. 2008.
  40. 25. Erhard R, Hong Hai D. Data Cleaning: Problems and Current Approaches. 2000.
  41. 27. Jiang T, Xiao Y, Wang X, Li Y. Leveraging communication information among readers for RFID data cleaning. Proceedings of the 12th international conference on Web-age information management; Wuhan, China. 2035588: Springer-Verlag; 2011. p. 201-13.
  42. 28. Roman-Gonzalez A, Datcu M. Data cleaning: Approaches for earth observation image information mining. ESA-EUSC-JRC 2011 Conference Proceedings; 30 March 2011; Ispra, Italien: JRC; 2011. p. 117-20.
  43. 29. Eredics P, Dobrowiecki TP, editors. Data cleaning for an intelligent greenhouse. Applied Computational Intelligence and Informatics (SACI), 2011 6th IEEE International Symposium on; 2011 19-21 May 2011.10.1109/saci.2011.5873017.
  44. 39. Marquardt G, Currier R, McHugh DM, Gavrilov D, Magera MJ, Matern D, Oglesbee D, Raymond K, Rinaldo P, Smith EH, Tortorelli S, Turgeon CT, Lorey F, Wilcken B, Wiley V, Greed LC, Lewis B, Boemer F, Schoos R, Marie S, Vincent MF, Sica YC, Domingos MT, Al-Thihli K, Sinclair G, Al-Dirbashi OY, Chakraborty P, Dymerski M, Porter C, Manning A, Seashore MR, Quesada J, Reuben A, Chrastina P, Hornik P, Atef Mandour I, Atty Sharaf SA, Bodamer O, Dy B, Torres J, Zori R, Cheillan D, Vianey-Saban C, Ludvigson D, Stembridge A, Bonham J, Downing M, Dotsikas Y, Loukas YL, Papakonstantinou V, Zacharioudakis GS, Barath A, Karg E, Franzson L, Jonsson JJ, Breen NN, Lesko BG, Berberich SL, Turner K, Ruoppolo M, Scolamiero E, Antonozzi I, Carducci C, Caruso U, Cassanello M, la Marca G, Pasquini E, Di Gangi IM, Giordano G, Camilot M, Teofoli F, Manos SM, Peterson CK, Mayfield Gibson SK, Sevier DW, Lee SY, Park HD, Khneisser I, Browning P, Gulamali-Majid F, Watson MS, Eaton RB, Sahai I, Ruiz C, Torres R, Seeterlin MA, Stanley EL, Hietala A, McCann M, Campbell C, Hopkins PV, de Sain-Van der Velden MG, Elvers B, Morrissey MA, Sunny S, Knoll D, Webster D, Frazier DM, McClure JD, Sesser DE, Willis SA, Rocha H, Vilarinho L, John C, Lim J, Caldwell SG, Tomashitis K, Castineiras Ramos DE, Cocho de Juan JA, Rueda Fernandez I, Yahyaoui Macias R, Egea-Mellado JM, Gonzalez-Gallego I, Delgado Pecellin C, Garcia-Valdecasas Bermejo MS, Chien YH, Hwu WL, Childs T, McKeever CD, Tanyalcin T, Abdulrahman M, Queijo C, Lemes A, Davis T, Hoffman W, Baker M, Hoffman GL. Enhanced interpretation of newborn screening results without analyte cutoff values. Genetics in medicine : official journal of the American College of Medical Genetics. 2012 Jul;14(7):648-55. PMID:22766634.
  45. 40. NTUH Newborn Screening Center. Newborn Screening Items. 2012; Archived at: http://www.ntuh.gov.tw/gene/nbsc/screen/item.html, http://www.webcitation.org/6Cbb70VUe.
  46. 42. Ko L-F, Lin J-C, Chen C-H, Chang J-S, Lai F, Hsu K-P, Yang T-H, Cheng P-H, Wen C-C, Chen J-L, Hsieh S-L, editors. HL7 middleware framework for healthcare information system. e-Health Networking, Applications and Services, 2006 HEALTHCOM 2006 8th International Conference on; 2006 17-19 Aug. 2006.10.1109/health.2006.246437.
  47. 46. Hsieh SL, Feipei L, Cheng PH, Chen JL, Lee HH, Tsai WN, Weng YC, Hsieh SH, Hsu KP, Ko LF, Yang TH, Chen CH, editors. An Integrated Healthcare Enterprise Information Portal and Healthcare Information System Framework. Engineering in Medicine and Biology Society, 2006 EMBS '06 28th Annual International Conference of the IEEE; 2006 Aug. 30 2006-Sept. 3 2006.10.1109/iembs.2006.260715.
  48. 47. Hsieh SH, Hsieh SL, Weng YC, Yang TH, Feipei L, Cheng PH, Ping XO, Jan MY, Lin JC, Peng CH, Huang KH, Ko LF, Chen CH, Hsu KP, editors. Middleware based Inpatient Healthcare Information System. Bioinformatics and Bioengineering, 2007 BIBE 2007 Proceedings of the 7th IEEE International Conference on; 2007 14-17 Oct. 2007.10.1109/bibe.2007.4375721.
  49. 48. Weng Y-C, Hsieh S-L, Hsieh S-H, Lai F, editors. Design and Enhance a Dynamic Healthcare Portal Site. Web Intelligence and Intelligent Agent Technology Workshops, 2007 IEEE/WIC/ACM International Conferences on; 2007 5-12 Nov. 2007.10.1109/wi-iatw.2007.66.
  50. 49. Chen Y-W, Lin C-J. Combining SVMs with Various Feature Selection Strategies. In: Guyon I, Nikravesh M, Gunn S, Zadeh L, editors. Feature Extraction: Springer Berlin Heidelberg; 2006. p. 315-24.
  51. 52. American Academy of Pediatrics. Newborn Screening Overview. 2010; Archived at: http://www.medicalhomeinfo.org/how/clinical_care/newborn_screening.aspx, http://www.webcitation.org/6Cj1n80vl.