Deep learning methods for digital pathology analysis are an effective way to address multiple clinical questions, from diagnosis to prediction of treatment outcomes. These methods have also been used to predict gene mutations from pathology images, but no comprehensive evaluation of their potential for extracting molecular features from histology slides has yet been performed. We show that HE2RNA, a model based on the integration of multiple data modes, can be trained to systematically predict RNA-Seq profiles from whole-slide images alone, without expert annotation. Through its interpretable design, HE2RNA provides virtual spatialization of gene expression, as validated by CD3-and CD20-staining on an independent dataset. The transcriptomic representation learned by HE2RNA can also be transferred on other datasets, even of small size, to increase prediction performance for specific molecular phenotypes. We illustrate the use of this approach in clinical diagnosis purposes such as the identification of tumors with microsatellite instability.

Accurate population models are needed to build very large-scale neural models, but their derivation is difficult for realistic networks of neurons, in particular when nonlinear properties are involved, such as conductance-based interactions and spike-frequency adaptation. Here, we consider such models based on networks of adaptive exponential integrate-and-fire excitatory and inhibitory neurons. Using a master equation formalism, we derive a mean-field model of such networks and compare it to the full network dynamics. The mean-field model is capable of correctly predicting the average spontaneous activity levels in asynchronous irregular regimes similar to in vivo activity. It also captures the transient temporal response of the network to complex external inputs. Finally, the mean-field model is also able to quantitatively describe regimes where high- and low-activity states alternate (up-down state dynamics), leading to slow oscillations. We conclude that such mean-field models are biologically realistic in the sense that they can capture both spontaneous and evoked activity, and they naturally appear as candidates to build very large-scale models involving multiple brain areas.