• 제목/요약/키워드: Precision medicine

검색결과 531건 처리시간 0.033초

Exome and genome sequencing for diagnosing patients with suspected rare genetic disease

  • Go Hun Seo;Hane Lee
    • Journal of Genetic Medicine
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    • 제20권2호
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    • pp.31-38
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    • 2023
  • Rare diseases, even though defined as fewer than 20,000 in South Korea, with over 8,000 rare Mendelian disorders having been identified, they collectively impact 6-8% of the global population. Many of the rare diseases pose significant challenges to patients, patients' families, and the healthcare system. The diagnostic journey for rare disease patients is often lengthy and arduous, hampered by the genetic diversity and phenotypic complexity of these conditions. With the advent of next-generation sequencing technology and clinical implementation of exome sequencing (ES) and genome sequencing (GS), the diagnostic rate for rare diseases is 25-50% depending on the disease category. It is also allowing more rapid new gene-disease association discovery and equipping us to practice precision medicine by offering tailored medical management plans, early intervention, family planning options. However, a substantial number of patients remain undiagnosed, and it could be due to several factors. Some may not have genetic disorders. Some may have disease-causing variants that are not detectable or interpretable by ES and GS. It's also possible that some patient might have a disease-causing variant in a gene that hasn't yet been linked to a disease. For patients who remain undiagnosed, reanalysis of existing data has shown promises in providing new molecular diagnoses achieved by new gene-disease associations, new variant discovery, and variant reclassification, leading to a 5-10% increase in the diagnostic rate. More advanced approach such as long-read sequencing, transcriptome sequencing and integration of multi-omics data may provide potential values in uncovering elusive genetic causes.

예측모형의 머신러닝 방법론과 통계학적 방법론의 비교: 영상의학 연구에서의 적용 (Machine Learning vs. Statistical Model for Prediction Modelling: Application in Medical Imaging Research)

  • 유리하;한경화
    • 대한영상의학회지
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    • 제83권6호
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    • pp.1219-1228
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    • 2022
  • 최근 영상의학 연구 분야에서 영상 인자를 포함한 임상 예측 모형의 수요가 증가하고 있고, 특히 라디오믹스 연구가 활발하게 이루어지면서 기존의 전통적인 회귀 모형뿐만 아니라 머신러닝을 사용하는 연구들이 많아지고 있다. 본 종설에서는 영상의학 분야에서 예측 모형 연구에 사용된 통계학적 방법과 머신 러닝 방법들을 조사하여 정리하고, 각 방법론에 대한 설명과 장단점을 살펴보고자 한다. 마지막으로 예측 모형 연구에서 분석 방법 선택에서의 고려사항을 정리해 보고자 한다.

Coated tube를 사용한 CA19-9 측정용 IRMA 시약의 평가 (Evaluation of Coated Tube CA19-9 IRMA kit)

  • 이현주;장현영;신선영;김희선;김태훈;이호영
    • 핵의학기술
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    • 제14권2호
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    • pp.208-211
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    • 2010
  • 현재 본원은 TFB사의 CA19-9 항체가 bead에 코팅되어있는 CA19-9 IRMA 시약을 사용하고있다. 이번에 TFB사에서 새로 개발된 CA19-9 항체가 polystyrene test tube에 코팅된 CA 19-9 IRMA 시약이 기존 TFB사의 bead를 사용하는 시약을 대체하여 사용할 수 있는지 시약의 성능을 평가하였다. 본원과 서울대학교병원 환자 56명의 검체를 대상으로 하여 TFB사의 기존 bead 방법을 사용한 시약과 새로 개발된 coated tube를 사용한 시약을 비교하여 상관계수와 회귀식을 구하고 coated tube를 사용한 시약의 정밀도, 회수율, 직선성, 민감도, Hook effect 를 확인하였다. 저, 중, 고역가 검체의 검사내 정밀도는 4.1%, 4.0%, 4.2%이고 검사간 정밀도는 7.6%, 4.3%, 7.8%이며 회수율은 모두 $100{\pm}10%$이다. 직선성은 우수하였고 분석적민감도는 0.3U/mL이었으며 9,020,000 U/mL 농도에서는 Hook effect가 나타나지 않았다. 또한 TFB사의 기존 bead를 사용한 방법과 비교하여 상관관계를 분석한 결과, y=0.9185x-0.953, 상관계수 $R^2$=0.9779이었다. 이번 연구를 통해 본원은 TFB사에서 새로 개발된 coated tube CA19-9 IRMA 시약이 검사 시간과 검사 과정에서 간편화되고 검사시 자동화기기를 사용할 수 있으며 기존 bead를 사용한 시약에 대체하여 사용할 수 있다고 판단하였다.

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Qualitative and Quantitative Magnetic Resonance Imaging Phenotypes May Predict CDKN2A/B Homozygous Deletion Status in Isocitrate Dehydrogenase-Mutant Astrocytomas: A Multicenter Study

  • Yae Won Park;Ki Sung Park;Ji Eun Park;Sung Soo Ahn;Inho Park;Ho Sung Kim;Jong Hee Chang;Seung-Koo Lee;Se Hoon Kim
    • Korean Journal of Radiology
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    • 제24권2호
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    • pp.133-144
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    • 2023
  • Objective: Cyclin-dependent kinase inhibitor (CDKN)2A/B homozygous deletion is a key molecular marker of isocitrate dehydrogenase (IDH)-mutant astrocytomas in the 2021 World Health Organization. We aimed to investigate whether qualitative and quantitative MRI parameters can predict CDKN2A/B homozygous deletion status in IDH-mutant astrocytomas. Materials and Methods: Preoperative MRI data of 88 patients (mean age ± standard deviation, 42.0 ± 11.9 years; 40 females and 48 males) with IDH-mutant astrocytomas (76 without and 12 with CDKN2A/B homozygous deletion) from two institutions were included. A qualitative imaging assessment was performed. Mean apparent diffusion coefficient (ADC), 5th percentile of ADC, mean normalized cerebral blood volume (nCBV), and 95th percentile of nCBV were assessed via automatic tumor segmentation. Logistic regression was performed to determine the factors associated with CDKN2A/B homozygous deletion in all 88 patients and a subgroup of 47 patients with histological grades 3 and 4. The discrimination performance of the logistic regression models was evaluated using the area under the receiver operating characteristic curve (AUC). Results: In multivariable analysis of all patients, infiltrative pattern (odds ratio [OR] = 4.25, p = 0.034), maximal diameter (OR = 1.07, p = 0.013), and 95th percentile of nCBV (OR = 1.34, p = 0.049) were independent predictors of CDKN2A/B homozygous deletion. The AUC, accuracy, sensitivity, and specificity of the corresponding model were 0.83 (95% confidence interval [CI], 0.72-0.91), 90.4%, 83.3%, and 75.0%, respectively. On multivariable analysis of the subgroup with histological grades 3 and 4, infiltrative pattern (OR = 10.39, p = 0.012) and 95th percentile of nCBV (OR = 1.24, p = 0.047) were independent predictors of CDKN2A/B homozygous deletion, with an AUC accuracy, sensitivity, and specificity of the corresponding model of 0.76 (95% CI, 0.60-0.88), 87.8%, 80.0%, and 58.1%, respectively. Conclusion: The presence of an infiltrative pattern, larger maximal diameter, and higher 95th percentile of the nCBV may be useful MRI biomarkers for CDKN2A/B homozygous deletion in IDH-mutant astrocytomas.

Development and Validation of MRI-Based Radiomics Models for Diagnosing Juvenile Myoclonic Epilepsy

  • Kyung Min Kim;Heewon Hwang;Beomseok Sohn;Kisung Park;Kyunghwa Han;Sung Soo Ahn;Wonwoo Lee;Min Kyung Chu;Kyoung Heo;Seung-Koo Lee
    • Korean Journal of Radiology
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    • 제23권12호
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    • pp.1281-1289
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    • 2022
  • Objective: Radiomic modeling using multiple regions of interest in MRI of the brain to diagnose juvenile myoclonic epilepsy (JME) has not yet been investigated. This study aimed to develop and validate radiomics prediction models to distinguish patients with JME from healthy controls (HCs), and to evaluate the feasibility of a radiomics approach using MRI for diagnosing JME. Materials and Methods: A total of 97 JME patients (25.6 ± 8.5 years; female, 45.5%) and 32 HCs (28.9 ± 11.4 years; female, 50.0%) were randomly split (7:3 ratio) into a training (n = 90) and a test set (n = 39) group. Radiomic features were extracted from 22 regions of interest in the brain using the T1-weighted MRI based on clinical evidence. Predictive models were trained using seven modeling methods, including a light gradient boosting machine, support vector classifier, random forest, logistic regression, extreme gradient boosting, gradient boosting machine, and decision tree, with radiomics features in the training set. The performance of the models was validated and compared to the test set. The model with the highest area under the receiver operating curve (AUROC) was chosen, and important features in the model were identified. Results: The seven tested radiomics models, including light gradient boosting machine, support vector classifier, random forest, logistic regression, extreme gradient boosting, gradient boosting machine, and decision tree, showed AUROC values of 0.817, 0.807, 0.783, 0.779, 0.767, 0.762, and 0.672, respectively. The light gradient boosting machine with the highest AUROC, albeit without statistically significant differences from the other models in pairwise comparisons, had accuracy, precision, recall, and F1 scores of 0.795, 0.818, 0.931, and 0.871, respectively. Radiomic features, including the putamen and ventral diencephalon, were ranked as the most important for suggesting JME. Conclusion: Radiomic models using MRI were able to differentiate JME from HCs.

Modification of the TNM Staging System for Stage II/III Gastric Cancer Based on a Prognostic Single Patient Classifier Algorithm

  • Choi, Yoon Young;Jang, Eunji;Seo, Won Jun;Son, Taeil;Kim, Hyoung-Il;Kim, Hyeseon;Hyung, Woo Jin;Huh, Yong-Min;Noh, Sung Hoon;Cheong, Jae-Ho
    • Journal of Gastric Cancer
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    • 제18권2호
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    • pp.142-151
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    • 2018
  • Purpose: The modification of the cancer classification system aimed to improve the classical anatomy-based tumor, node, metastasis (TNM) staging by considering tumor biology, which is associated with patient prognosis, because such information provides additional precision and flexibility. Materials and Methods: We previously developed an mRNA expression-based single patient classifier (SPC) algorithm that could predict the prognosis of patients with stage II/III gastric cancer. We also validated its utilization in clinical settings. The prognostic single patient classifier (pSPC) differentiates based on 3 prognostic groups (low-, intermediate-, and high-risk), and these groups were considered as independent prognostic factors along with TNM stages. We evaluated whether the modified TNM staging system based on the pSPC has a better prognostic performance than the TNM 8th edition staging system. The data of 652 patients who underwent gastrectomy with curative intent for gastric cancer between 2000 and 2004 were evaluated. Furthermore, 2 other cohorts (n=307 and 625) from a previous study were assessed. Thus, 1,584 patients were included in the analysis. To modify the TNM staging system, one-grade down-staging was applied to low-risk patients according to the pSPC in the TNM 8th edition staging system; for intermediate- and high-risk groups, the modified TNM and TNM 8th edition staging systems were identical. Results: Among the 1,584 patients, 187 (11.8%), 664 (41.9%), and 733 (46.3%) were classified into the low-, intermediate-, and high-risk groups, respectively, according to the pSPC. pSPC prognoses and survival curves of the overall population were well stratified, and the TNM stage-adjusted hazard ratios of the intermediate- and high-risk groups were 1.96 (95% confidence interval [CI], 1.41-2.72; P<0.001) and 2.54 (95% CI, 1.84-3.50; P<0.001), respectively. Using Harrell's C-index, the prognostic performance of the modified TNM system was evaluated, and the results showed that its prognostic performance was better than that of the TNM 8th edition staging system in terms of overall survival (0.635 vs. 0.620, P<0.001). Conclusions: The pSPC-modified TNM staging is an alternative staging system for stage II/III gastric cancer.

인증표준물질(CRM)을 이용한 방사면역측정법의 회수율 평가 (The Evaluation of Recovery Rate of Radioimmunoassay Using Certified Reference Material (CRM))

  • 최성희;신선영;임소희;홍미경;노경운;김진의
    • 핵의학기술
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    • 제18권1호
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    • pp.158-162
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    • 2014
  • 공인된 기구에 의해 발급된 문서를 동반하는 인증표준물질은 특성값과 추정값의 신뢰정도를 나타내는 연계 불확도, 그리고 측정한 결과가 명시된 불확정 정도의 범위 내에서 국가 측정 또는 국제측정표준에 일치되도록 연속적으로 비교하고 교정하는 소급성을 제공하는 표준물질이다. 회수율 검사는 검체를 측정하여 얻은 값이 참값에서 얼마만큼 벗어났는지의 차이를 말하며 키트의 정확도를 반영한다. 이러한 인증표준물질을 가지고 회수율 검사를 하는 것은 체외 방사면역진단키트의 정확성을 보여주며 이러한 평가는 매우 중요하다. 인증표준물질은 NIBSC (National Institute for biological standard and control, United Kingdom)와 IRMM (Institute for Reference Materials and Measurements, Belgium)에서 구입하였고 검사 종목은 T4, Ferritin, PSA, Prolactin, AFP 그리고 TSH으로 총 6종목이다. T4는 IRMM의 표준물질을 사용하였고 나머지 종목은 NIBSC의 표준물질을 사용하였다. C-1 (저농도), C-2 (중농도), C-3 (고농도) 3 level로 제조하여 본원에서 사용하는 키트를 이용하여 4회 측정하였다. WHO 인증표준물질을 이용한 회수율 측정에서 T4 90%, Ferritin 88%, PSA 94%, Prolactin 99%, AFP 94%, TSH 93%였다. 6개 종목의 회수율 측정에서 88-99%로 양호한 결과를 보였다. 핵의학 체외진단키트의 정확성을 높이기 위해서 이 연구가 다른 검사실의 키트로 확장되어 검사가 되어야 하고 검사실간에도 교류가 필요하다. 인증표준물질을 이용한 체외진단키트의 회수율 평가가 앞으로도 지속되어야 하며 결과의 정확성은 환자의 만족의 증가로 이어질 것으로 기대한다.

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LC-MS/MS를 이용한 우유 중 덱사메타손의 잔류 분석법 개발 (Development of an Analytical Method for the Determination of Dexamethasone in Bovine Milk Using Liquid Chromatography Coupled to Tandem Mass Spectrometry)

  • 차춘남;박은기;유창열;이성중;손송이;김석;이후장
    • 한국식품위생안전성학회지
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    • 제32권5호
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    • pp.418-423
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    • 2017
  • 본 연구는 우유 중에서 덱사메타손을 효과적으로 정량분석하기 위한 LC-MS/MS법을 확립하고 이를 검증하기 위해 수행되었다. 확립된 LC-MS/MS에 대해 특이성, 검출한계, 정량한계, 정확도 및 정밀도에 대한 검증을 통하여 유효성을 확인하였다. 표준용액을 이용하여 검량성을 작성한 결과, $r^2$ > 0.999 이상의 직선성을 확인하였고, 덱사메타손에 대한 검출한계와 정량한계는 각각 0.15와 0.5 ng/mL이었다. 또한, 회수율은 98.9-109.6%로 나타났으며, 상대표준편차는 1.7-4.4%로 나타나 정확성이 우수하였으며, 이는 식품의약품안전처의 잔류동물용의약품 분석법에서 제시한 기준에 모두 적합한 수준이었다. 따라서 본 연구를 통해 개발된 LC-MS/MS법은 향후 우유 중 덱사메타손을 분석하는데 효과적으로 활용될 수 있을 것으로 사료된다.

증기화광산란 검출기를 이용한 콩 함유 수용성 탄수화물의 분석 (Determination of Soluble Carbohydrates in Soybean Seeds Using High Performance Liquid Chromatography with Evaporative Light Scattering Detection)

  • 김경하;황영선;안경근;김기쁨;김민지;홍승범;문중경;정명근
    • 한국식품영양과학회지
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    • 제43권7호
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    • pp.1062-1067
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    • 2014
  • 콩 함유 수용성 탄수화물의 동시분석 시 증기화광산란검출법(HPLC/ELSD) 및 굴절율검출법(HPLC/RID)의 분석 효율성, 정밀성 및 재현성을 상호 비교, 평가하여 콩 함유 수용성 탄수화물의 효율적 분석방법을 제공하고자 하였다. HPLC/ELSD 분석법 적용 시 콩 함유 수용성 탄수화물의 정량한계(LOQ)를 확인한 결과 5.6~7.6 mg/kg 범위를 나타낸 반면, RID는 16.2~33.9 mg/kg 범위를 나타내어 HPLC/ELSD 분석법이 RID 분석법 대비 감도가 향상된 양상을 확인하였고, intra-day(n=10) 및 inter-day(n=5) 분석재현성 평가에서도 피크의 머무름 시간(Rt.) 및 면적(peak area) 모두 최대 2.5% 미만의 변이계수를 나타내어 높은 분석 재현성을 확인할 수 있었다. 또한 농도별 표준시약을 이용하여 검량식의 직선성을 확인한 결과 모든 성분이 고도의 직선성($R^2$ >0.999)이 유지되어 정량적 분석이 가능함을 확인하였다. 콩 함유 수용성 탄수화물의 함량을 HPLC/ELSD 및 RID 방법으로 상호 비교한 결과 HPLC/ELSD 분석법을 적용하였을 경우 RID 분석법 대비 각 수용성 탄수화물의 함량이 더 높게 평가됨을 확인할 수 있었다.

Design of a Propagation Wave Type Microrobot for Moving on the Slippery Surface

  • Kim, Eui-Jin;Park, Jong-Hyeon
    • 제어로봇시스템학회:학술대회논문집
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    • 제어로봇시스템학회 2003년도 ICCAS
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    • pp.2072-2077
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    • 2003
  • Animal-like robots are serving an important role as a linkage between biology and engineering. So, in this paper, we aim to develop a biomimetic microrobot that mimics the locomotion mechanism of a gastropod. This microrobot has 3 DOF (x, y translation and rotation), and has small size, unlimited traveling range, high resolution and low cost. Its movement can be made using propagation wave that is generated by the controllable sinusoidal voltage source and piezoelectric effects. This soft motion that can be generated by propagation wave and piezoelectric mechanism would be useful for the motion on the slippery surface. So we modeled the propagation wave mechanism including piezoelectric effect and friction on the contact surface, and could know the velocity of the microrobot is dependent on the driving frequency, input voltage peak, propagation wavelength and surface friction coefficient. With these results we design the microrobot, and accomplish its fabrication and experimentation. The development of this microrobot shall be aimed to design an autonomous moving actuator like animal. Also it can be used from micromanipulation system technology to biology and medicine.

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