This issue of Nature Computational Science includes a Focus that highlights recent advancements, challenges, and opportunities in the development and use of digital twins across different domains.

Digital twins hold immense promise in accelerating scientific discovery, but the publicity currently outweighs the evidence base of success. We summarize key research opportunities in the computational sciences to enable digital twin technologies, as identified by a recent National Academies of Sciences, Engineering, and Medicine consensus study report.

The application of digital twins in industry has become increasingly common, but not without important challenges to be addressed by the research community.

Although digital twins first originated as models of physical systems, they are rapidly being applied to social systems, such as cities. This Perspective discusses the development and use of digital twins for urban planning.

Cooperation is not merely a dyadic phenomenon, it also includes multi-way social interactions. A mathematical framework is developed to study how the structure of higher-order interactions influences cooperative behavior.

This study introduces SANGO, a method for accurate single-cell annotation leveraging genomic sequences around accessibility peaks within single-cell ATAC sequencing data. SANGO consistently outperforms existing methods across diverse datasets for identification of cell type and detection of unknown tumor cells. SANGO enables the discovery of cell-type-specific functional insights through expression enrichment, cis-regulatory chromatin interactions and motif enrichment analyses.

A fast and versatile three-dimensional cell-based model, called SimuCell3D, is developed for high-resolution simulations of large and complex biological tissues. SimuCell3D natively integrates intra- and extracellular entities, including extracellular matrix, nuclei and polarized cell surfaces.

A method is developed for the directional optimization of multiple properties without prior knowledge on their nature. Using a large ligand dataset, diverse metal complexes are found along the Pareto front of vast chemical spaces.

Andre Berndt and colleagues introduce a machine learning approach to enhance the biophysical characteristics of genetically encoded fluorescent indicators, deriving and testing in vitro new GCaMP mutations that surpass the performance of existing fast GCaMP indicators.

M-OFDFT is a deep learning implementation of orbital-free density functional theory (OFDFT) that achieves DFT-level accuracy on molecular systems with lower cost complexity, and can extrapolate to much larger molecules than those seen during training.

Wildfires have increased in frequency and intensity due to climate change and have had severe impacts on the built environment worldwide. Moving forward, models should take inspiration from epidemic network modeling to predict damage to individual buildings and understand the impact of different mitigations on the community vulnerability in a network setting.

This issue of Nature Computational Science includes a Focus that highlights recent advancements, challenges, and opportunities in the development and use of digital twins across different domains.

Digital twins hold immense promise in accelerating scientific discovery, but the publicity currently outweighs the evidence base of success. We summarize key research opportunities in the computational sciences to enable digital twin technologies, as identified by a recent National Academies of Sciences, Engineering, and Medicine consensus study report.

Digital twins of Earth have the capability to offer versatile access to detailed information on our changing world, helping societies to adapt to climate change and to manage the effects of local impacts, globally. Nevertheless, human interaction with digital twins requires advances in computational science, particularly where complex geophysical data is turned into information to support decision making.

Urban digital twins hold immense promise as live computational models of cities, synthesizing diverse knowledge, streaming data, and supporting decisions towards more inclusive planning and policy. The size, heterogeneity, and open-ended character of cities, however, pose many difficult questions, at the frontiers of what is currently possible in computational science. Overcoming these challenges provides pathways for fundamental progress in the field and a proving ground for its economic value and social relevance.

Dr Zhimei Sun – professor of Materials Science and Engineering at Beihang University – talks to Nature Computational Science about her career trajectory, her research on computational materials science and materials informatics, as well as her advice to young women scientists in these fields.