Tziki Kam

Applications of Artificial Intelligence (AI) are revolutionizing biomedical research and healthcare by offering data-driven predictions that assist in diagnoses. Supervised learning systems are trained on large datasets to predict outcomes for new test cases. However, they typically do not provide an indication of the reliability of these predictions, even though error estimates are integral to model development. Here, we introduce a novel method to identify regions in the feature space that diverge from training data, where an AI model may perform poorly. We utilize a compact precompiled structure that allows for fast and direct access to confidence scores in real time at the point of use without requiring access to the training data or model algorithms. As a result, users can determine when to trust the AI model's outputs, while developers can identify where the model's applicability is limited. We validate our approach using simulated data and several biomedical case studies, demonstrating that our approach provides fast confidence estimates (0.965). These estimates can be easily added to real-world AI applications. We argue that providing confidence estimates should be a standard practice for all AI applications in public use.

Cryoelectron tomography of the cell nucleus using scanning transmission electron microscopy and deconvolution processing technology has highlighted a large-scale, 100-to 300-nm interphase chromosome structure, which is present throughout the nucleus. This study further documents and analyzes these chromosome structures. The paper is divided into four parts: 1) evidence (preliminary) for a unified interphase chromosome structure; 2) a proposed unified interphase chromosome architecture; 3) organization as chromosome territories (e.g., fitting the 46 human chromosomes into a 10-μm-diame-ter nucleus); and 4) structure unification into a polytene chromosome architecture and lampbrush chromosomes. Finally, the paper concludes with a living light microscopy cell study showing that the G1 nucleus contains very similar structures throughout. The main finding is that this chromosome structure appears to coil the 11-nm nucleosome fiber into a defined hollow structure, analogous to a Slinky helical spring [https://en.wikipedia.org/wiki/Slinky; motif used in Bowerman et al., eLife 10, e65587 (2021)]. This Slinky architecture can be used to build chromosome territories, extended to the polytene chromosome structure, as well as to the structure of lampbrush chromosomes.