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. arXiv:1806.07814v3 [cond-mat.stat-mech]

In this paper we aim at characterizing the effect of stochastic fluctuations on the distribution of the energy exchanged by a quantum system with an external environment under sequences of quantum measurements performed at random times. Both quenched and annealed averages are considered. The information about fluctuations is encoded in the quantum-heat probability density function, or equivalently in its characteristic function, whose general expression for a quantum system with arbitrary Hamiltonian is derived. We prove that, when a stochastic protocol of measurements is applied, the quantum Jarzynski equality is obeyed. Therefore, the fluctuation relation is robust against the presence of randomness in the times intervals between measurements. Then, for the paradigmatic case of a two-level system, we analytically characterize the quantum-heat transfer. Particular attention is devoted to the limit of large number of measurements and to the effects caused by the stochastic fluctuations. The relation with the stochastic Zeno regime is also discussed.

Charting a biological atlas of an organ, such as the brain, requires us to spatially-resolve whole transcriptomes of single cells, and to relate such cellular features to the histological and anatomical scales. Single-cell and single-nucleus RNA-Seq (sc/snRNA-seq) can map cells comprehensively5,6, but relating those to their histological and anatomical positions in the context of an organ’s common coordinate framework remains a major challenge and barrier to the construction of a cell atlas7–10. Conversely, Spatial Transcriptomics allows for in-situ measurements11–13 at the histological level, but at lower spatial resolution and with limited sensitivity. Targeted in situ technologies1–3 solve both issues, but are limited in gene throughput which impedes profiling of the entire transcriptome. Finally, as samples are collected for profiling, their registration to anatomical atlases often require human supervision, which is a major obstacle to build pipelines at scale. Here, we demonstrate spatial mapping of cells, histology, and anatomy in the somatomotor area and the visual area of the healthy adult mouse brain. We devise Tangram, a method that aligns snRNA-seq data to various forms of spatial data collected from the same brain region, including MERFISH1, STARmap2, smFISH3, and Spatial Transcriptomics4 (Visium), as well as histological images and public atlases. Tangram can map any type of sc/snRNA-seq data, including multi-modal data such as SHARE-seq data5, which we used to reveal spatial patterns of chromatin accessibility. We equipped Tangram with a deep learning computer vision pipeline, which allows for automatic identification of anatomical annotations on histological images of mouse brain. By doing so, Tangram reconstructs a genome-wide, anatomically-integrated, spatial map of the visual and somatomotor area with ∼30,000 genes at single-cell resolution, revealing spatial gene expression and chromatin accessibility patterning beyond current limitation of in-situ technologies.

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