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Solid tumors are spatially heterogeneous in their genetic, molecular, and cellular composition, but recent spatial profiling studies have mostly charted genetic and RNA variation in tumors separately. To leverage the potential of RNA to identify copy number alterations (CNAs), we develop SlideCNA, a computational tool to extract CNA signals from sparse spatial transcriptomics data with near single cellular resolution. SlideCNA uses expression-aware spatial binning to overcome sparsity limitations while maintaining spatial signal to recover CNA patterns. We test SlideCNA on simulated and real Slide-seq data of (metastatic) breast cancer and demonstrate its potential for spatial subclone detection.

Although metastatic disease is the leading cause of cancer-related deaths, its tumor microenvironment remains poorly characterized due to technical and biospecimen limitations. In this study, we assembled a multi-modal spatial and cellular map of 67 tumor biopsies from 60 patients with metastatic breast cancer across diverse clinicopathological features and nine anatomic sites with detailed clinical annotations. We combined single-cell or single-nucleus RNA sequencing for all biopsies with a panel of four spatial expression assays (Slide-seq, MERFISH, ExSeq and CODEX) and H&E staining of consecutive serial sections from up to 15 of these biopsies. We leveraged the coupled measurements to provide reference points for the utility and integration of different experimental techniques and used them to assess variability in cell type composition and expression as well as emerging spatial expression characteristics across clinicopathological and methodological diversity. Finally, we assessed spatial expression and co-localization features of macrophage populations, characterized three distinct spatial phenotypes of epithelial-to-mesenchymal transition and identified expression programs associated with local T cell infiltration versus exclusion, showcasing the potential of clinically relevant discovery in such maps. Single-nucleus and single-cell RNA sequencing plus spatial profiling with four methods of core biopsies from 60 patients with metastatic breast cancer reveal patient-specific gene expression programs of breast cancer metastases that are maintained across time, site of metastasis and spatial profiling method, with spatial phenotypes correlating with microenvironmental features.

Solid tumors are spatially heterogeneous in their genetic, molecular and cellular composition, and this variation can be meaningful for diagnosis, prognosis and therapy. Recent spatial profiling studies have mostly charted genetic and RNA variation in tumors separately. To leverage the potential of RNA to identify copy number alterations (CNAs), we developed SlideCNA, a computational tool to extract sparse spatial CNA signals from spatial transcriptomics data, using expression-aware spatial binning. We test SlideCNA on simulated and real Slide-seq data of metastatic breast cancer (MBC) and demonstrate its potential for spatial sub-clone detection.Competing Interest StatementA.R. is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas, and was an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics and Asimov until July 31, 2020. O.R.R and A.R. are employees of Genentech from August 1, 2020 and October 19, 2020, respectively, and have equity in Roche. O.R.R. and A.R. are named inventors on multiple patents filed by the Broad Institute in the area of single cell and spatial genomics. S.R. has received research support from KITE/Gilead and Bristol-Myers-Squibb and is on the SAB of Immunitas Therapeutics.Footnotes* https://github.com/dkzhang777/SlideCNA

Dryland ecosystems cover 40% of our planet's land surface, support billions of people, and are responding rapidly to climate and land use change. These expansive systems also dominate core aspects of Earth's climate, storing and exchanging vast amounts of water, carbon, and energy with the atmosphere. Despite their indispensable ecosystem services and high vulnerability to change, drylands are one of the least understood ecosystem types, partly due to challenges studying their heterogeneous landscapes and misconceptions that drylands are unproductive “wastelands.” Consequently, inadequate understanding of dryland processes has resulted in poor model representation and forecasting capacity, hindering decision making for these at‐risk ecosystems. NASA satellite resources are increasingly available at the higher resolutions needed to enhance understanding of drylands' heterogeneous spatiotemporal dynamics. NASA's Terrestrial Ecology Program solicited proposals for scoping a multi‐year field campaign, of which Adaptation and Response in Drylands (ARID) was one of two scoping studies selected. A primary goal of the scoping study is to gather input from the scientific and data end‐user communities on dryland research gaps and data user needs. Here, we provide an overview of the ARID team's community engagement and how it has guided development of our framework. This includes an ARID kickoff meeting with over 300 participants held in October 2023 at the University of Arizona to gather input from data end‐users and scientists. We also summarize insights gained from hundreds of follow‐up activities, including from a tribal‐engagement focused workshop in New Mexico, conference town halls, intensive roundtables, and international engagements. Plain Language Summary Drylands are landscapes with limited water availability, which cover 40% of Earth's land surfaces, support billions of humans, and play a substantial role in Earth's weather and climate systems. However, these ecosystems are under threat from droughts and heatwaves. They are also poorly understood because of challenges measuring their highly diverse vegetation types and interspersed vegetation cover and because of incorrect perceptions that they are unimportant “wastelands.” These limitations make it challenging to manage their landscapes and quantify how drylands are driving Earth's weather and climate. NASA solicited proposals for a multi‐year field campaign, of which Adaptation and Response in Drylands (ARID) was one of two scoping studies selected. The ARID scoping study aims to design a plan for how NASA satellite, aircraft, and field instruments can be used to better understand dryland ecosystems and their response to change. A primary scoping goal is to engage with scientists and data‐users, especially those who manage land, to understand research and management priorities in drylands. Here, we discuss details of our meeting with over 300 scientists and data‐users in Tucson, AZ in October 2023. We also highlight feedback from our tribal‐focused workshop in New Mexico, conference town halls, and international meetings. Key Points Adaptation and Response in Drylands (ARID) is a 1‐year scoping study for a multi‐year NASA Terrestrial Ecology dryland field campaign An ARID workshop was held in Tucson, Arizona in October 2023 with more than 30 data end‐users and 300 scientists in attendance Further input from hundreds of researchers and end‐users was obtained through workshops, conference townhalls, and tribal engagement

Près de la ville de Yinchuan dans la région autonome chinoise du Ningxia Hui, au pied du mont Helan, un cimetière abrite neuf tombes d'empereurs de la dynastie Xixia (1038-1227) ainsi que plus de deux cents tombes annexes. Chacune des tombes impériales comprend plusieurs constructions protégées par une enceinte, dont un monument plein qui devait avoir à l'origine l'aspect d'une pagode. Outre sa forme originale, ce monument est situé dans la partie nord-ouest de l'enceinte, non au centre ; d'autre part, il ne surplombe pas la chambre funéraire, dont il semble pourtant destiné à marquer la présence. Une telle disposition rompt avec toutes les traditions de l'architecture impériale en Chine comme dans sa périphérie. Ce double décalage au sol et en sous-sol, qui n'a pas arrêté l'attention des chercheurs, nous servira de fil conducteur pour mieux comprendre les singularités du cimetière impérial xixia. Une analyse architecturale des tombes, puis une interprétation à partir d'éléments religieux et politiques nous permettront ainsi de mettre en lumière différentes influences à l'æuvre dans la conception de ces tombes, dans le choix du lieu, et de mesurer l'apport original de la civilisation tangoute. The Xixia (Western Xia) imperial necropolis, nestled against the Helan Mountains, lies about 35 km west of Yinchuan, the present capital of the Ningxia Hui Autonomous Region of China. The necropolis contains the tombs of nine emperors of the Xixia dynasty (1038-1227) and more than 200 auxiliary tombs. Each imperial tomb comprises several constructions, including an imposing solid mound originally resembling a pagoda. In addition to having a distinctive shape, the monument is built in the north-western part of the inner precinct of the tomb and not at its centre. Furthermore, and most surprisingly, it does not indicate the location of the underground chamber, for it is not placed directly on top of the latter. These features have never been observed in traditional Chinese imperial funerary architecture, nor in those of other bordering states. The paucity of information about these singularities led to our current research, which is focused on an architectural analysis of the xixia imperial tombs. By integrating religious and political considerations into our interpretation, we seek to reveal the influences at work in the conception of this necropolis and the choice of its location. Our analysis also assesses the extent and the originality of the Tangut contribution. 在屮國寧复问族治區銀川市附近的賀蘭山麓，有一片墓地， 容納了西夏王朝（(1038-1227) 的九座帝王陵墓和二百多座陪葬墓。每座帝王陵墓包含若干建築單元， 被圍墙保護起來， 其屮的陵臺原本應為塔式建築。除造型別具一格而外， 陵臺偏處陵城西北， 而不是建在陵城的中央。另外， 陵臺應該標示出墓室的位置，但是它並沒 有疗接矗立在墓室之上。這樣的佈局在中國和華夏鄰邦的所有皇家建築傳統屮都 兄不到。地上、地下的這種雙重錯位並沒有引起研究人員的重視， 我們將通過研 究這個特點來更好地理解西夏帝王陵的獨特之處。我們對陵墓做了建築學上的 分析， 乂根據宗教和政治因素做了_ 釋， 由此可讓我們弄明白有哪些因素影響了 陵墓的設計和選址， 並對黨頂义明的原創之處進行評估。 今日の寧夏回族自治区の首都銀川から約35 キロ西に向かった賀蘭山脈の麓に、 西夏の皇帝の墳墓がある。ここには、西夏王朝（(1038—1227) 年） の9 人の皇帝 の墓と、それに附属する 200 以上の墓が発見されている。それぞれの皇帝の墳墓 には、壁に囲まれた內部にいくつかの建造物が建てられており、中でも当初は塔の 形をしていたと考えられる内部空間のない塚が建てられている。これは特有の形を しているだけでなく、敷地内の中央ではなく北西側に立てられており、さらに、地下 の墓室の存在を表わすために建てられたはずなのに、その真上には置かれて 、な い、という注目すべき特徴をもっている。このような配置は、中国の皇帝の墳墓の伝 統や周辺地域の国家の墳墓でも他に例がない。この塚の地上の位置、および地下 の墓室に対する位置について、これまで注意が払われたことはほとんどなかった が、それを検討することによって、西夏皇帝の墳墓の特殊性をより明確にするこ とができる。本論では、西夏皇帝の墳墓の建築学的な分析に基づき、また、宗教 および政治的な側面に注目することにより、この墓場が造られた背景に存在した 観念、あるいはその場所の選択がどのような影響の下にあったのかを明らかにす ることを試みる。それはまた、タンダート文化の特徴に光を当てる作業でもある。