Cryo-electron microscopy (cryo-EM) remains pivotal in structural biology, yet the task of protein particle picking, integral for 3D protein structure construction, is laden with manual inefficiencies. While recent AI tools such as Topaz and crYOLO are advancing the field, they do not fully address the challenges of cryo-EM images, including low contrast, complex shapes, and heterogeneous conformations. This study explored prompt-based learning to adapt the state-of-the-art image segmentation foundation model Segment Anything Model (SAM) for cryo-EM. This focus was driven by the desire to optimize model performance with a small number of labeled data without altering pre-trained parameters, aiming for a balance between adaptability and foundational knowledge retention. Through trials with three prompt-based learning strategies, namely head prompt, prefix prompt, and encoder prompt, we observed enhanced performance and reduced computational requirements compared to the fine-tuning approach. This work not only highlights the potential of prompting SAM in protein identification from cryo-EM micrographs but also suggests its broader promise in biomedical image segmentation and object detection.

A random dot product graph (RDPG) is a generative model for networks in which vertices correspond to positions in a latent Euclidean space and edge probabilities are determined by the dot products of the latent positions. We consider RDPGs for which the latent positions are randomly sampled from an unknown $1$-dimensional submanifold of the latent space. In principle, restricted inference, i.e., procedures that exploit the structure of the submanifold, should be more effective than unrestricted inference; however, it is not clear how to conduct restricted inference when the submanifold is unknown. We submit that techniques for manifold learning can be used to learn the unknown submanifold well enough to realize benefit from restricted inference. To illustrate, we test a hypothesis about the Fr\'{e}chet mean of a small community of vertices, using the complete set of vertices to infer latent structure. We propose test statistics that deploy the Isomap procedure for manifold learning, using shortest path distances on neighborhood graphs constructed from estimated latent positions to estimate arc lengths on the unknown $1$-dimensional submanifold. Unlike conventional applications of Isomap, the estimated latent positions do not lie on the submanifold of interest. We extend existing convergence results for Isomap to this setting and use them to demonstrate that, as the number of auxiliary vertices increases, the power of our test converges to the power of the corresponding test when the submanifold is known.