Data-based detection and quantification of causation in complex, nonlinear dynamical systems is of paramount importance to science, engineering, and beyond. Inspired by the widely used methodology in recent years, the cross-map-based techniques, we develop a general framework to advance towards a comprehensive understanding of dynamical causal mechanisms, which is consistent with the natural interpretation of causality. In particular, instead of measuring the smoothness of the cross-map as conventionally implemented, we define causation through measuring the scaling law for the continuity of the investigated dynamical system directly. The uncovered scaling law enables accurate, reliable, and efficient detection of causation and assessment of its strength in general complex dynamical systems, outperforming those existing representative methods. The continuity scaling-based framework is rigorously established and demonstrated using datasets from model complex systems and the real world.
Rui DongYau Mathematical Sciences Center, Tsinghua University, Beijing, China; Yanqi Lake Beijing Institute of Mathematical Sciences and Applications, Beijing, ChinaTaojun HuDepartment of Biostatistics, School of Public Health, Peking University, Beijing 100191, ChinaYunjun ZhangDepartment of Biostatistics, School of Public Health, Peking University, Beijing 100191, ChinaYang Li Chongqing School, University of Chinese Academy of Sciences, Chongqing 400020, ChinaXiao-Hua Zhou Department of Biostatistics, School of Public Health, Peking University, Beijing 100191, China; Beijing International Center for Mathematical Research, Peking University, Beijing 100191, China
Data Analysis, Bio-Statistics, Bio-Mathematicsmathscidoc:2204.42002
Omicron, the latest SARS-CoV-2 Variant of Concern (VOC), first appeared in Africa in November 2021. At present, the question of whether a new VOC will out-compete the currently predominant variant is important for governments seeking to determine if current surveillance strategies and responses are appropriate and reasonable. Based on both virus genomes and daily-confirmed cases, we compare the additive differences in growth rates and reproductive numbers (R_0) between VOCs and their predominant variants through a Bayesian framework and phylo-dynamics analysis. Faced with different variants, we evaluate the effects of current policies and vaccinations against VOCs and predominant variants. The model also predicts the date on which a VOC may become dominant based on simulation and real data in the early stage. The results suggest that the overall additive difference in growth rates of B.1.617.2 and predominant variants was 0.44 (95% confidence interval, 95% CI: −0.38, 1.25) in February 2021, and that the VOC had a relatively high R_0. The additive difference in the growth rate of BA.1 in the United Kingdom was 6.82 times the difference between Delta and Alpha, and the model successfully predicted the dominating process of Alpha, Delta and Omicron. Current vaccination strategies remain similarly effective against Delta compared to the previous variants. Our model proposes a reliable Bayesian framework to predict the spread trends of VOCs based on early-stage data, and evaluates the effects of public health policies, which may help us better prepare for the upcoming Omicron variant, which is now spreading at an unprecedented speed.
Rui DongYau Mathematical Sciences Center, Tsinghua University, Beijing, China; Yanqi Lake Beijing Institute of Mathematical Sciences and Applications, Beijing, ChinaShaojun PeiDepartment of Mathematical Sciences, Tsinghua University, Beijing, ChinaMengcen GuanDepartment of Mathematical Sciences, Tsinghua University, Beijing, ChinaShek-Chung YauInformation Technology Services Center, The Hong Kong University of Science and Technology, Kowloon, Hong Kong, ChinaChangchuan YinDepartment of Mathematics, Statistics and Computer Science, University of Illinois at Chicago, Chicago, IL, United StatesRong L. HeDepartment of Biological Sciences, Chicago State University, Chicago, IL, United StatesStephen S.-T. YauDepartment of Mathematical Sciences, Tsinghua University, Beijing, China; Yanqi Lake Beijing Institute of Mathematical Sciences and Applications, Beijing, China
Data Analysis, Bio-Statistics, Bio-Mathematicsmathscidoc:2204.42001
A comprehensive description of human genomes is essential for understanding human evolution and relationships between modern populations. However, most published literature focuses on local alignment comparison of several genes rather than the complete evolutionary record of individual genomes. Combining with data from the 1,000 Genomes Project, we successfully reconstructed 2,504 individual genomes and propose Divided Natural Vector method to analyze the distribution of nucleotides in the genomes. Comparisons based on autosomes, sex chromosomes and mitochondrial genomes reveal the genetic relationships between populations, and different inheritance pattern leads to different phylogenetic results. Results based on mitochondrial genomes confirm the “out-of-Africa” hypothesis and assert that humans, at least females, most likely originated in eastern Africa. The reconstructed genomes are stored on our server and can be further used for any genome-scale analysis of humans (http://yaulab.math.tsinghua.edu.cn/2022_1000genomesprojectdata/). This project provides the complete genomes of thousands of individuals and lays the groundwork for genome-level analyses of the genetic relationships between populations and the origin of humans.
Xiaojie QiuWhitehead Institute for Biomedical Research, Cambridge, MA, USAYan ZhangDepartment of Computational and System Biology, University of Pittsburgh, Pittsburgh, PA, USAJorge D. Martin-RufinoBroad Institute of MIT and Harvard, Cambridge, MA, USAChen WengWhitehead Institute for Biomedical Research, Cambridge, MA, USAShayan HosseinzadehDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USAJianhua XingDepartment of Computational and System Biology, University of Pittsburgh, Pittsburgh, PA, USAJonathan WeissmanWhitehead Institute for Biomedical Research, Cambridge, MA, USA
Data Analysis, Bio-Statistics, Bio-Mathematicsmathscidoc:2202.42001
Single-cell (sc)RNA-seq, together with RNA velocity and metabolic labeling, reveals cellular states and transitions at unprecedented resolution. Fully exploiting these data, however, requires kinetic models capable of unveiling governing regulatory functions. Here, we introduce an analytical framework dynamo (https://github.com/aristoteleo/dynamo-release), which infers absolute RNA velocity, reconstructs continuous vector fields that predict cell fates, employs differential geometry to extract underlying regulations, and ultimately predicts optimal reprogramming paths and perturbation outcomes. We highlight dynamo’s power to overcome fundamental limitations of conventional splicing-based RNA velocity analyses to enable accurate velocity estimations on a metabolically labeled human hematopoiesis scRNA-seq dataset. Furthermore, differential geometry analyses reveal mechanisms driving early megakaryocyte appearance and elucidate asymmetrical regulation within the PU.1-GATA1 circuit. Leveraging the least-action-path method, dynamo accurately predicts drivers of numerous hematopoietic transitions. Finally, in silico perturbations predict cell-fate diversions induced by gene perturbations. Dynamo, thus, represents an important step in advancing quantitative and predictive theories of cell-state transitions.
Forest above-ground biomass (AGB) can be estimated based on light detection and ranging (LiDAR) point clouds. This paper introduces an accurate and detailed quantitative structure model (AdQSM), which can estimate the AGB of large tropical trees. AdQSM is based on the reconstruction of 3D tree models from terrestrial laser scanning (TLS) point clouds. It represents a tree as a set of closed and complete convex polyhedra. We use AdQSM to model 29 trees of various species (total 18 species) scanned by TLS from three study sites (the dense tropical forests of Peru, Indonesia, and Guyana). The destructively sampled tree geometry measurement data is used as reference values to evaluate the accuracy of diameter at breast height (DBH), tree height, tree volume, branch volume, and AGB estimated from AdQSM. After AdQSM reconstructs the structure and volume of each tree, AGB is derived by combining the wood density of the specific tree species from destructive sampling. The AGB estimation from AdQSM and the post-harvest reference measurement data show a satisfying agreement. The coefficient of variation of root mean square error (CV-RMSE) and the concordance correlation coefficient (CCC) are 20.37% and 0.97, respectively. AdQSM provides accurate tree volume estimation, regardless of the characteristics of the tree structure, without major systematic deviations. We compared the accuracy of AdQSM and TreeQSM in modeling the volume of 29 trees. The tree volume from AdQSM is compared with the reference value, and the determination coefficient (R2), relative bias (rBias), and CV-RMSE of tree volume are 0.96, 6.98%, and 22.62%, respectively. The tree volume from TreeQSM is compared with the reference value, and the R2, relative Bias (rBias), and CV-RMSE of tree volume are 0.94, −9.69%, and 23.20%, respectively. The CCCs between the volume estimates based on AdQSM, TreeQSM, and the reference values are 0.97 and 0.96. AdQSM also models the branches in detail. The volume of branches from AdQSM is compared with the destructive measurement reference data. The R2, rBias, and CV-RMSE of the branches volume are 0.97, 12.38%, and 36.86%, respectively. The DBH and height of the harvested trees were used as reference values to test the accuracy of AdQSM’s estimation of DBH and tree height. The R2, rBias, and CV-RMSE of DBH are 0.94, −5.01%, and 9.06%, respectively. The R2, rBias, and CV-RMSE of the tree height were 0.95, 1.88%, and 5.79%, respectively. This paper provides not only a new QSM method for estimating AGB based on TLS point clouds but also the potential for further development and testing of allometric equations.