Fig. 6: Our analysis identified FRRS1, CTRAM, SCGB3A1, FAM92B/CIBAR2, and TMEFF2 as potential AD risk genes. Two (CRTAM and SCGB3A1) of the validated genes are relevant to immune mechanisms involving TREM2-TYROBP and IL-1β/TNFα axis, respectively. Two (FRRS1 and FAM92B) are considered dark genes. TMEFF2 is involved in MTOR-APP regulation. | Communications Biology

Fig. 6: Our analysis identified FRRS1, CTRAM, SCGB3A1, FAM92B/CIBAR2, and TMEFF2 as potential AD risk genes. Two (CRTAM and SCGB3A1) of the validated genes are relevant to immune mechanisms involving TREM2-TYROBP and IL-1β/TNFα axis, respectively. Two (FRRS1 and FAM92B) are considered dark genes. TMEFF2 is involved in MTOR-APP regulation.

From: Machine learning prediction and tau-based screening identifies potential Alzheimer’s disease genes relevant to immunity

Fig. 6

a. Heatmap showing the summary of the top genes vs bottom genes, via three different validations done on all twenty MPxgb(AD) predicted genes, as well as bottom predicted genes. The heat map colors represent the p value statistical significance. * = p value ≤ 0.05; ** = p value ≤ 0.005; *** = p value ≤ 0.0005. (1) The first row shows the results from the iPSNs-based validation where the mRNA levels of GOI are either increased (red), decreased (blue) or no change (white) in sAD2.1 iPSNs compared to control AX0018 iPSNs. (2) The second row is mRNA levels for the MPxgb(AD) predicted GOI are either increased (red), decreased (blue) or no change (white) in human autopsy brains. The third row is the results from the human autopsy brains of sporadic AD vs age-matched healthy controls, where the MPxgb(AD) predicted proteins of interest (POI) are either increased (red), decreased (blue), not detectable (gray with an x) or not significant (white). (3) The last two rows show the results from SH-SY5Y siRNA knockdown experiments, where the knockdown of MPxgb(AD) predicted GOI significantly reduced AT8 (blue) and/or AT180 (blue) levels. b. * Corresponds with statistical significance levels in (a) and represents one unit level or point; ** denote two points, and *** represents three points. Thus, the ranking system is determined by the p values and sets each GOI with a total score calculated from each screening experiment. Note, the siRNA experiments were not included in the final rank score. Moreover, the final list is labeled as top ranked with 3pts total score being the highest (also labeled with their original predicted rank number), FRRS1 and CTRAM are tied for our top significant AD-relevant genes. With 2pts total score, SCGB3A1, FAM92B/CIBAR2, and TMEFF2 are ranked second. c. STRING protein network connectivity analysis of the three (CRTAM, SCGB3A1, and TMEFF2) of the top five validated genes show interactions with well-established TREM2-TYROBP, IL-1β/TNFα, (both immune axes) and MTOR-APP relevant to AD, respectively.

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