Lastly, we aimed to characterize the performance of our method specifically in cases where the bridge dataset was missing specific cell populations, or exhibited low data quality. Using the BMMC multiome benchmark dataset, we removed all plasmacytoid dendritic cells (pDC) from the multi-omic dataset, and repeated bridge integration. We found that this modification did not alter the annotations or confidence scores of non-pDC cells in the query, but that pDC query cells did exhibit a drop in annotation performance (94.4% annotated as pDC using the full bridge, 83.5% annotated as pDC using the depleted bridge dataset). However, we found that these query cells also exhibited a specific and sharp drop in prediction confidence (average prediction score of 0.907 using the full bridge, 0.514 using the depleted bridge), demonstrating that our procedure correctly reduced the confidence of prediction when the underlying assumptions were not met. We repeated this analysis after separately depleting three additional cell populations (B cells, CD8+ T, CD14+ monocytes), and observed similar results (Supplementary Fig. 4a). Moreover, we found that substantially reducing bridge data quality by discarding UMI
