Importance of Electrode Selection and Number in Reconstructing Standard Twelve Lead Electrocardiograms.

Many clinical and consumer electrocardiogram (ECG) devices collect fewer electrodes than the standard twelve-lead ECG and either report less information or employ algorithms to reconstruct a full twelve-lead signal. We assessed the optimal electrode selection and number that minimizes redundant information collection while maximizing reconstruction accuracy. We employed a validated deep learning model to reconstruct ECG signals from 250 different patients in the PTB database. Different numbers and combinations of electrodes were removed from the ECG before reconstruction to measure the effect of electrode inclusion on reconstruction accuracy. The Left Leg (LL) electrode registered the largest drop in average reconstruction accuracy, from an R2 of 0.836 when the LL was included to 0.737 when excluded. Additionally, we conducted a correlation analysis to identify leads that behave similarly. We demonstrate that there exists a high correlation between leads I, II, aVL, aVF, V4, V5, and V6, which all occupy the bottom right quadrant in an ECG axis interpretation, and likely contain redundant information. Based on our analysis, we recommend the prioritization of electrodes RA, LA, LL, and V3 in any future lead collection devices, as they appear most important for full ECG reconstruction.

Post-translational covalent assembly of CAR and synNotch receptors for programmable antigen targeting.

Chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors are engineered cell-surface receptors that sense a target antigen and respond by activating T cell receptor signaling or a customized gene program, respectively. Here, to expand the targeting capabilities of these receptors, we develop "universal" receptor systems for which receptor specificity can be directed post-translationally via covalent attachment of a co-administered antibody bearing a benzylguanine (BG) motif. A SNAPtag self-labeling enzyme is genetically fused to the receptor and reacts with BG-conjugated antibodies for covalent assembly, programming antigen recognition. We demonstrate that activation of SNAP-CAR and SNAP-synNotch receptors can be successfully targeted by clinically relevant BG-conjugated antibodies, including anti-tumor activity of SNAP-CAR T cells in vivo in a human tumor xenograft mouse model. Finally, we develop a mathematical model to better define the parameters affecting universal receptor signaling. SNAP receptors provide a powerful strategy to post-translationally reprogram the targeting specificity of engineered cells.