Dataset Information

Predicting venous thromboembolism risk from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges.

ABSTRACT: Genetics play a key role in venous thromboembolism (VTE) risk, however established risk factors in European populations do not translate to individuals of African descent because of the differences in allele frequencies between populations. As part of the fifth iteration of the Critical Assessment of Genome Interpretation, participants were asked to predict VTE status in exome data from African American subjects. Participants were provided with 103 unlabeled exomes from patients treated with warfarin for non-VTE causes or VTE and asked to predict which disease each subject had been treated for. Given the lack of training data, many participants opted to use unsupervised machine learning methods, clustering the exomes by variation in genes known to be associated with VTE. The best performing method using only VTE related genes achieved an area under the ROC curve of 0.65. Here, we discuss the range of methods used in the prediction of VTE from sequence data and explore some of the difficulties of conducting a challenge with known confounders. In addition, we show that an existing genetic risk score for VTE that was developed in European subjects works well in African Americans.

SUBMITTER: McInnes G

PROVIDER: S-EPMC7047641 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Predicting venous thromboembolism risk from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges.

McInnes Gregory G Daneshjou Roxana R Katsonis Panagiostis P Lichtarge Olivier O Srinivasan Rajgopal R Rana Sadhna S Radivojac Predrag P Mooney Sean D SD Pagel Kymberleigh A KA Stamboulian Moses M Jiang Yuxiang Y Capriotti Emidio E Wang Yanran Y Bromberg Yana Y Bovo Samuele S Savojardo Castrense C Martelli Pier Luigi PL Casadio Rita R Pal Lipika R LR Moult John J Brenner Steven E SE Altman Russ R

Human mutation 20190624 9

Genetics play a key role in venous thromboembolism (VTE) risk, however established risk factors in European populations do not translate to individuals of African descent because of the differences in allele frequencies between populations. As part of the fifth iteration of the Critical Assessment of Genome Interpretation, participants were asked to predict VTE status in exome data from African American subjects. Participants were provided with 103 unlabeled exomes from patients treated with war ...[more]

PMID: 31140652

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Project description:Background Venous thromboembolism (VTE) is a threat to the prognosis of tumor patients, especially for critically ill patients. No uniform standard model of VTE risk for critically ill patients with tumors was formatted by now. We thus analyzed risk factors of VTE from the perspectives of patient, tumor, and treatment and assessed the predictive value of the ICU-VTE score, which consisted of six independent risk factors (central venous catheterization, 5 points; immobilization ≥ 4 days, 4 points; prior VTE, 4 points; mechanical ventilation, 2 points; lowest hemoglobin during hospitalization ≥ 90 g/L, 2 points; and baseline platelet count > 250,000/μL, 1 points). Methods We evaluated the data of tumor patients admitted to the intensive care unit of the Peking University Cancer Hospital between November 2011 and January 2022; 560 cases who received VTE-related screening during hospitalization were chosen for this retrospective study. Results The inhospital VTE occurrence rate in our cohort was 55.7% (312/560), with a median interval from ICU admission to VTE diagnosis of 8.0 days. After the multivariate logistic regression analysis, several factors were proved to be significantly associated with inhospital VTE: age ≥ 65 years, high tumor grade (G3–4), medical diseases, fresh frozen plasma transfusion, and anticoagulant prophylaxis. The medium-high risk group according to the ICU-VTE score was positively correlated with VTE when compared with the low-risk group (9–18 points vs. 0–8 points; OR, 3.13; 95% CI, 2.01–4.85, P < 0.001). The AUC of the ICU-VTE scores according to the ROC curve was 0.714 (95% CI, 0.67–0.75, P < 0.001). Conclusions The ICU-VTE score, as well as tumor grade, might assist in the assessment of inhospital VTE risk for critically ill patients with tumors. The predictive accuracy might be improved when combining two of them; further follow-up researches are needed to confirm it. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02705-z.

Project description:AimTo characterise venous thromboembolism (VTE) in gastrointestinal cancer and assess the clinical utility of risk stratification scoring.MethodsWe performed a retrospective analysis using electronic patient records of 910 gastro-oesophageal (GO) cancer and 1299 colorectal cancer (CRC) patients referred to a tertiary cancer centre to identify the incidence of VTE, its relationship to chemotherapy and impact on survival. VTE risk scores were calculated using the Khorana index. Patients were classified as low risk (0 points), intermediate risk (1 to 2 points) or high risk (3 points). Data was analysed to determine the sensitivity of the Khorana score to predict VTE.ResultsThe incidence of VTE was 8.9% for CRC patients and 9.7% for GO cancer patients. Pulmonary emboli (PE) were more common in advanced than in localised CRC (50% vs 21% of events respectively) and lower limb deep vein thrombosis (DVT) were more common in localised than in advanced CRC (62% vs 39% of events respectively). The median time to VTE from cancer diagnosis was 8.3 mo for CRC patients compared to 6.7 mo in GO cancer. In localised CRC median time to VTE was 7.1 mo compared with 10.1 mo in advanced CRC. In contrast in GO cancer, the median time to VTE was 12.5 mo in localised disease and 6.8 mo in advanced disease. No survival difference was seen between patients with and without VTE in this cohort. The majority of patients with CRC in whom VTE was diagnosed had low or intermediate Khorana risk score (94% for localised and 97% in advanced CRC). In GO cancer, all patients scored either intermediate or high risk due to the primary site demonstrating a limitation of the risk assessment score in discriminating high and low risk patients with GO cancers. Additional risk factors were identified in this cohort including surgery, chemotherapy or hospital admission. Overall, 81% of patients with CRC and 77% of patients with GO cancer had one or more of these factors within 4 wk prior to diagnosis VTE. These should be factored into clinical risk assessment scores.ConclusionThe Khorana score has low sensitivity for thrombotic events in CRC and cannot discriminate low risk patients in high risk cancer sites such as GO cancer.

Dataset Information

Predicting venous thromboembolism risk from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges.

Publications

Predicting venous thromboembolism risk from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges.

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