Charting an organs’ biological atlas requires us to spatially resolve the entire single-cell transcriptome, and to relate such cellular features to the anatomical scale. Single-cell and single-nucleus RNA-seq (sc/snRNA-seq) can profile cells comprehensively, but lose spatial information. Spatial transcriptomics allows for spatial measurements, but at lower resolution and with limited sensitivity. Targeted in situ technologies solve both issues, but are limited in gene throughput. To overcome these limitations we present Tangram, a method that aligns sc/snRNA-seq data to various forms of spatial data collected from the same region, including MERFISH, STARmap, smFISH, Spatial Transcriptomics (Visium) and histological images. Tangram can map any type of sc/snRNA-seq data, including multimodal data such as those from SHARE-seq, which we used to reveal spatial patterns of chromatin accessibility. We demonstrate Tangram on healthy mouse brain tissue, by reconstructing a genome-wide anatomically integrated spatial map at single-cell resolution of the visual and somatomotor areas.

Invasiveness of quantum measurements is a genuinely quantum mechanical feature that is not necessarily detrimental: Here we show how quantum measurements can be used to fuel a cooling engine. We illustrate quantum measurement cooling (QMC) by means of a prototypical two-stroke two-qubit engine which interacts with a measurement apparatus and two heat reservoirs at different temperatures. We show that feedback control is not necessary for operation while entanglement must be present in the measurement projectors. We quantify the probability that QMC occurs when the measurement basis is chosen randomly, and find that it can be very large as compared to the probability of extracting energy (heat engine operation), while remaining always smaller than the most useless operation, namely, dumping heat in both baths. These results show that QMC can be very robust to experimental noise. A possible low-temperature solid-state implementation that integrates circuit QED technology with circuit quantum thermodynamics technology is presented.

Establishing causal relationships between genetic alterations of human cancers and specific phenotypes of malignancy remains a challenge. We sequentially introduced mutations into healthy human melanocytes in up to five genes spanning six commonly disrupted melanoma pathways, forming nine genetically distinct cellular models of melanoma. We connected mutant melanocyte genotypes to malignant cell expression programs in vitro and in vivo, replicative immortality, malignancy, rapid tumor growth, pigmentation, metastasis, and histopathology. Mutations in malignant cells also affected tumor microenvironment composition and cell states. Our melanoma models shared genotype-associated expression programs with patient melanomas, and a deep learning model showed that these models partially recapitulated genotype-associated histopathological features as well. Thus, a progressive series of genome-edited human cancer models can causally connect genotypes carrying multiple mutations to phenotype.

The third law of thermodynamics, also known as the Nernst unattainability principle, puts a fundamental bound on how close a system, whether classical or quantum, can be cooled to a temperature near to absolute zero. On the other hand, a fundamental assumption of quantum computing is to start each computation from a register of qubits initialized in a pure state, i.e., at zero temperature. These conflicting aspects, at the interface between quantum computing and thermodynamics, are often overlooked or, at best, addressed only at a single-qubit level. In this Letter, we argue how the existence of a small but finite effective temperature, which makes the initial state a mixed state, poses a real challenge to the fidelity constraints required for the scaling of quantum computers. Our theoretical results, carried out for a generic quantum circuit with $N$-qubit input states, are validated by test runs performed on a real quantum processor.

Quantum machine learning (QML) is a young but rapidly growing field where quantum information meets machine learning. Here, we will introduce a new QML model generalising the classical concept of reinforcement learning to the quantum domain, i.e. quantum reinforcement learning (QRL). In particular, we apply this idea to the maze problem, where an agent has to learn the optimal set of actions in order to escape from a maze with the highest success probability. To perform the strategy optimisation, we consider a hybrid protocol where QRL is combined with classical deep neural networks. In particular, we find that the agent learns the optimal strategy in both the classical and quantum regimes, and we also investigate its behaviour in a noisy environment. It turns out that the quantum speedup does robustly allow the agent to exploit useful actions also at very short time scales, with key roles played by the quantum coherence and the external noise. This new framework has the high potential to be applied to perform different tasks (e.g. high transmission/processing rates and quantum error correction) in the new-generation noisy intermediate-scale quantum (NISQ) devices whose topology engineering is starting to become a new and crucial control knob for practical applications in real-world problems. This work is dedicated to the memory of Peter Wittek.