Journal: Nature Communications

Article Title: Deep phenotyping of Alzheimer’s disease leveraging electronic medical records identifies sex-specific clinical associations

doi: 10.1038/s41467-022-28273-0

Figure Lengend Snippet: Top row: UMAP of all patients (AD and controls), with each dot representing a patient, colored by AD status ( a top left, b top left) or by sex ( a top right, b top right). Middle and bottom rows: violin plots show the distribution of patients with AD and controls along the UMAP principal components for UCSF ( a ) and Mount Sinai ( b ), and p -values determined from comparing distributions with a two-sided Mann–Whitney U -test. Alzheimer vs Control: UCSF p -value 2.4e−20 (component 1) and 3.1e−258 (component 2). Mount Sinai p -value 3.3e−20 and 1.4e−275. Male vs female: UCSF p -value 9.2e−5 and 0.01. Mount Sinai p -value 7.0e−12 and 3.6e−9.

Article Snippet: In the validation EMR, 18 of 23 (78.25%) significant medications found at UCSF are significant in females at Mount Sinai, and 13 of 16 (81.25%) in males (two-sided Fisher’s exact or Chi-squared test, Bonferroni-corrected p -value < 0.05 based upon significant medications at UCSF within a group).

Techniques: MANN-WHITNEY, Control

Journal: Nature Communications

Article Title: Deep phenotyping of Alzheimer’s disease leveraging electronic medical records identifies sex-specific clinical associations

doi: 10.1038/s41467-022-28273-0

Figure Lengend Snippet: a Volcano plot for Level 2 categories (top) and full diagnosis names (bottom) compared between AD and control cohorts using two-sided Fisher’s exact or Chi-squared test. p -value cutoff is Bonferroni-corrected ( p -value < 2e−8 and 1e−6) with log2 odds ratio cutoff of 1 for AD-enriched (pink) or log2 odds ratio cutoff of −1 for control-enriched (green) and remaining significant diagnoses in blue. Some of the top significant diagnoses are labeled. b Top, a Manhattan plot with full diagnosis names colored by ICD-10-CM categories with significance determined by two-sided Fisher’s exact or Chi-squared test with Bonferroni-corrected p -value threshold of 0.05. Some of the top diagnoses in each category are labeled. Bottom, the percentage of diagnosis in each ICD-10-CM category is significant. c Diagnosis AD vs. control odds ratio correlation plots between UCSF and Mount Sinai for Level 2 diagnosis categories and full diagnosis names that are significant at UCSF (two-sided Fisher’s exact or Chi-squared test, Bonferroni-corrected p -value threshold of 0.05). Each dot represents a category or diagnosis, and dots in orange are significant at Mount Sinai with (two-sided Fisher’s exact or Chi-squared test with Bonferroni-corrected p -value threshold of 0.05 based on the number of significant UCSF diagnoses).

Article Snippet: In the validation EMR, 18 of 23 (78.25%) significant medications found at UCSF are significant in females at Mount Sinai, and 13 of 16 (81.25%) in males (two-sided Fisher’s exact or Chi-squared test, Bonferroni-corrected p -value < 0.05 based upon significant medications at UCSF within a group).

Techniques: Biomarker Discovery, Control, Labeling

Journal: Nature Communications

Article Title: Deep phenotyping of Alzheimer’s disease leveraging electronic medical records identifies sex-specific clinical associations

doi: 10.1038/s41467-022-28273-0

Figure Lengend Snippet: a Full diagnosis names compared between patients with AD and controls within each sex. The log2 of the odds ratio for each sex is plotted on the axis, and points are colored by significance (Bonferroni-corrected, p -value cutoff > 3e−6). b Miami plot of the diagnosis names grouped by sex and ICD-10-CM categories. Select top diagnoses are labeled, with diagnosis names colored by significance as female-only (red), male-only (blue), or significant in both sexes (black). c Correlation plots of AD vs. control odds ratios between UCSF and Mount Sinai for diagnoses that are significant at UCSF for each sex group (two-sided Fisher’s exact or Chi-squared test, Bonferroni-corrected p -value threshold of 0.05). Each dot represents a diagnosis, and dots in orange are significant at Mount Sinai (two-sided Fisher’s exact or Chi-squared test with Bonferroni-corrected p -value threshold of 0.05 based on the number of significant UCSF diagnoses for each sex group).

Article Snippet: In the validation EMR, 18 of 23 (78.25%) significant medications found at UCSF are significant in females at Mount Sinai, and 13 of 16 (81.25%) in males (two-sided Fisher’s exact or Chi-squared test, Bonferroni-corrected p -value < 0.05 based upon significant medications at UCSF within a group).

Techniques: Biomarker Discovery, Labeling, Control

Journal: Nature Communications

Article Title: Deep phenotyping of Alzheimer’s disease leveraging electronic medical records identifies sex-specific clinical associations

doi: 10.1038/s41467-022-28273-0

Figure Lengend Snippet: a Volcano plot for generic medication names compared between AD and control cohorts using two-sided Fisher’s exact or Chi-squared test. p -value cutoff is Bonferroni-corrected ( p -value < 2e−5) with odds ratio cutoff at 2 for AD-enriched (pink) or 1/2 for control-enriched (green). Remaining significant diagnoses are in blue. b Log–log plot of generic medication names compared between AD and control cohorts within each sex. The log of the odds ratio for each sex is plotted on the axis, with points colored by significance based upon two-sided Fisher’s exact or Chi-squared test with Bonferroni-corrected threshold of 0.05 if female-only (red), male-only (blue), or both (black). c AD vs control (top) and sex-specific (bottom) odds ratio correlation plots between UCSF and Mount Sinai for medications significant at UCSF (two-sided Fisher’s exact or Chi-squared test with Bonferroni-corrected p -value threshold of 0.05). Each dot represents a medication, and the dots in orange are significant at Mount Sinai (two-sided Fisher’s exact or Chi-squared test with Bonferroni-corrected p -value threshold of 0.05 based on the number of significant UCSF diagnoses in each group). d Heatmap of lab values filtered on significance at UCSF in AD vs control comparison across sex-specific groups at UCSF and Mount Sinai. Labs are clustered with light blue lines representing significant cluster breaks (family-wise error rate (FWER)-corrected p -value 0.05). Text color represents significant labs at both institutions (purple), significant among females only at UCSF (red), or significant between AD vs controls at UCSF only (black). Heatmap colors represent z -score of the average median value across the 4 groups at each institution.

Article Snippet: In the validation EMR, 18 of 23 (78.25%) significant medications found at UCSF are significant in females at Mount Sinai, and 13 of 16 (81.25%) in males (two-sided Fisher’s exact or Chi-squared test, Bonferroni-corrected p -value < 0.05 based upon significant medications at UCSF within a group).

Techniques: Control, Medications, Comparison

Journal: Nature Communications

Article Title: Deep phenotyping of Alzheimer’s disease leveraging electronic medical records identifies sex-specific clinical associations

doi: 10.1038/s41467-022-28273-0

Figure Lengend Snippet: Visualization of patient cohort identification from the UCSF EMR and methods for deep phenotyping and enrichment analysis. Validation analysis is done with Mount Sinai EMR to assess correlations.

Article Snippet: In the validation EMR, 18 of 23 (78.25%) significant medications found at UCSF are significant in females at Mount Sinai, and 13 of 16 (81.25%) in males (two-sided Fisher’s exact or Chi-squared test, Bonferroni-corrected p -value < 0.05 based upon significant medications at UCSF within a group).

Techniques: Biomarker Discovery

Journal: Nature Communications

Article Title: Deep phenotyping of Alzheimer’s disease leveraging electronic medical records identifies sex-specific clinical associations

doi: 10.1038/s41467-022-28273-0

Figure Lengend Snippet: Patient demographics.

Article Snippet: In the validation EMR, 18 of 23 (78.25%) significant medications found at UCSF are significant in females at Mount Sinai, and 13 of 16 (81.25%) in males (two-sided Fisher’s exact or Chi-squared test, Bonferroni-corrected p -value < 0.05 based upon significant medications at UCSF within a group).

Techniques: Control