Results of the high-value case biological test analyses between very high TPMT activity patients and other patients with normal and low TPMT activity.

<p>Global approach: a low-value case is defined as at least one occurrence, over the study period, of biological test result below the low threshold defined in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003405#pcbi-1003405-t001" target="_blank">Table 1</a>. Frequency-based approach: for a given patient, the frequency of low-value encounters is defined as the number of encounters with at least one occurrence below the low threshold divided by the number of encounters (mean low-value encounter frequencies are reported).</p><p>TPMTa: thiopurine <i>S</i>-methyltransferase activity. lowTPMTa: low TPMTa (<8.5 nmol/h/mL red blood cells); vhTPMTa: very high TPMTa (≥15.0 nmol/h/mL red blood cells); nTPMTa: normal TPMTa (in between).</p

Schematic representation of a PheWAS on a quantitative trait, analyzing ICD codes and biological test results.

<p>PheWAS: Phenome-wide association study; ICD: International classification of diseases; TPMT: thiopurine <i>S</i>-methyltransferase. Patients are assigned to a group depending on the level of a quantitative trait (<i>e.g.</i> TPMT activity). ICD codes and biological test results are screened to find systematic differences between the groups.</p

Pseudo-Manhattan plot of −log10 (P-values) for the 11 biological tests between very high TPMT activity patients and other TPMT activity patients.

<p>Using the global approach, a high-value case, resp. low-value case, is defined as at least one occurrence of a biological test result above, resp. below, the high or low threshold. Low-value case analyses have not been performed on alanine aminotransferase, aspartate aminotransferase and gamma glutamyl-transpeptidase test results, as a low threshold is not relevant for these tests. The dotted line represents a P-value of 0.05. Grey triangles represent the results above the high threshold and black triangles represent the results below the low threshold.</p

Additional file 1: of Next generation phenotyping using narrative reports in a rare disease clinical data warehouse

Extracted phenotypical concepts per cohort. For each cohort, we list the top50 concepts ranked by Frequency and TF-IDF. The first column is the UMLS code of the phenotypical concepts, the second column is the French preferred terms, the third column is the English preferred terms, the fourth column is the frequencies score (FREQ), the fifth column is the TF-IDF score, the sixth column is the rank of the concept sorted by the frequency score, the seventh column is the rank of the concept sorted by the TF-IDF score and the eighth column is the expert evaluation (1: relevant concept, 0: none relevant concept). (XLS 93 kb

Manhattan plot of −log10 (P-values) for the 771 ICD-9-CM based aggregated codes between very high TPMT activity patients and other TPMT activity patients.

<p>ICD-9-CM: International classification of diseases 9 clinically modified; TPMT: thiopurine <i>S</i>-methyltransferase. The dotted line represents a P-value of 0.05 and the dashed line represents the FDR corrected level of significance for q = 0.2.</p

Description of electronic health records (EHRs) of the thiopurine S-methyltransferase activity tested patients (TPMT cohort) and the control patients.

<p>Control patients are randomly extracted from the clinical data warehouse (CDW) of the Hôpital européen Georges Pompidou.</p><p>TPMTa: thiopurine <i>S</i>-methyltransferase activity; low TPMTa: <8.5 nmol/h/mL red blood cells; very high TPMTa: ≥15.0 nmol/h/mL red blood cells; normal TPMTa: in between.</p

Manhattan plot of −log10 (P-values) for the 256 ICD-10 based aggregated codes between very high TPMT activity patients and other TPMT activity patients.

<p>ICD-10: International classification of diseases 10; TPMT: thiopurine <i>S</i>-methyltransferase. The dotted line represents a P-value of 0.05 and the dashed line represents the FDR corrected level of significance for q = 0.2.</p

Flow chart.

<p>HEGP CDW: Clinical data warehouse from Hôpital Européen Georges Pompidou, France. TPMT Cohort: patients with a thiopurine S-methyltransferase (TPMT) activity assessment in HEGP between January 2000 and July 2013. ICD: International Statistical Classification of Diseases and Related Health Problems. PheWAS: phenome-wide association study.</p

Proportion and associated risk ratio of complication classes for the young compared to old adult with ARDS.

Proportion and associated risk ratio of complication classes for the young compared to old adult with ARDS.</p

Medication class.

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