Pub Date : 2024-07-10DOI: 10.1038/s43588-024-00653-0
Vadim K. Karnaukhov, Dmitrii S. Shcherbinin, Anton O. Chugunov, Dmitriy M. Chudakov, Roman G. Efremov, Ivan V. Zvyagin, Mikhail Shugay
T cell receptor (TCR) recognition of foreign peptides presented by major histocompatibility complex protein is a major event in triggering the adaptive immune response to pathogens or cancer. The prediction of TCR–peptide interactions has great importance for therapy of cancer as well as infectious and autoimmune diseases but remains a major challenge, particularly for novel (unseen) peptide epitopes. Here we present TCRen, a structure-based method for ranking candidate unseen epitopes for a given TCR. The first stage of the TCRen pipeline is modeling of the TCR–peptide–major histocompatibility complex structure. Then a TCR–peptide residue contact map is extracted from this structure and used to rank all candidate epitopes on the basis of an interaction score with the target TCR. Scoring is performed using an energy potential derived from the statistics of TCR–peptide contact preferences in existing crystal structures. We show that TCRen has high performance in discriminating cognate versus unrelated peptides and can facilitate the identification of cancer neoepitopes recognized by tumor-infiltrating lymphocytes. TCRen predicts TCR specificity by modeling the TCR–peptide–MHC structure and estimating the TCR–peptide interaction energy using a statistical potential. The use of structural information allows TCRen to generalize to unseen epitopes, such as cancer neoepitopes.
{"title":"Structure-based prediction of T cell receptor recognition of unseen epitopes using TCRen","authors":"Vadim K. Karnaukhov, Dmitrii S. Shcherbinin, Anton O. Chugunov, Dmitriy M. Chudakov, Roman G. Efremov, Ivan V. Zvyagin, Mikhail Shugay","doi":"10.1038/s43588-024-00653-0","DOIUrl":"10.1038/s43588-024-00653-0","url":null,"abstract":"T cell receptor (TCR) recognition of foreign peptides presented by major histocompatibility complex protein is a major event in triggering the adaptive immune response to pathogens or cancer. The prediction of TCR–peptide interactions has great importance for therapy of cancer as well as infectious and autoimmune diseases but remains a major challenge, particularly for novel (unseen) peptide epitopes. Here we present TCRen, a structure-based method for ranking candidate unseen epitopes for a given TCR. The first stage of the TCRen pipeline is modeling of the TCR–peptide–major histocompatibility complex structure. Then a TCR–peptide residue contact map is extracted from this structure and used to rank all candidate epitopes on the basis of an interaction score with the target TCR. Scoring is performed using an energy potential derived from the statistics of TCR–peptide contact preferences in existing crystal structures. We show that TCRen has high performance in discriminating cognate versus unrelated peptides and can facilitate the identification of cancer neoepitopes recognized by tumor-infiltrating lymphocytes. TCRen predicts TCR specificity by modeling the TCR–peptide–MHC structure and estimating the TCR–peptide interaction energy using a statistical potential. The use of structural information allows TCRen to generalize to unseen epitopes, such as cancer neoepitopes.","PeriodicalId":74246,"journal":{"name":"Nature computational science","volume":"4 7","pages":"510-521"},"PeriodicalIF":12.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141567219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-10DOI: 10.1038/s43588-024-00654-z
Miaozhe Huo, Yuepeng Jiang, Shuai Cheng Li
A method leverages protein structural data to predict T-cell receptor–peptide interactions for unseen peptide epitopes, which can be particularly useful for applications in cancer immunotherapy, autoimmunity studies, and vaccine design.
有一种方法利用蛋白质结构数据来预测未见肽表位的 T 细胞受体与肽的相互作用，这对癌症免疫疗法、自身免疫研究和疫苗设计中的应用特别有用。
{"title":"Unlocking T-cell receptor–epitope insights with structural analysis","authors":"Miaozhe Huo, Yuepeng Jiang, Shuai Cheng Li","doi":"10.1038/s43588-024-00654-z","DOIUrl":"10.1038/s43588-024-00654-z","url":null,"abstract":"A method leverages protein structural data to predict T-cell receptor–peptide interactions for unseen peptide epitopes, which can be particularly useful for applications in cancer immunotherapy, autoimmunity studies, and vaccine design.","PeriodicalId":74246,"journal":{"name":"Nature computational science","volume":"4 7","pages":"475-476"},"PeriodicalIF":12.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141567352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transformation theory, active control and inverse design have been mainstream in creating free-form metamaterials. However, existing frameworks cannot simultaneously satisfy the requirements of isotropic, passive and forward design. Here we propose a forward conformality-assisted tracing method to address the geometric and single-physical-field constraints of conformal transformation. Using a conformal mesh composed of orthogonal streamlines and isotherms (or isothermal surfaces), this method quasi-analytically produces free-form metamaterials using only isotropic media. The geometric nature of this approach allows for universal regulation of both dissipative thermal fields and non-dissipative electromagnetic fields. We experimentally demonstrate free-form thermal cloaking in both two and three dimensions. Additionally, the multi-physical functionalities of our method, including optical cloaking, bending and thermo-electric transparency, confirm its broad applicability. Our method features improvements in efficiency, accuracy and adaptability over previous approaches. This study provides an effective method for designing complex metamaterials with arbitrary shapes across various physical domains. Here a conformality-assisted tracing method is proposed to devise free-form and three-dimensional conformal metamaterials, featuring accuracy and efficiency in handling complex geometry and adaptability to various diffusion and wave fields.
{"title":"Free-form and multi-physical metamaterials with forward conformality-assisted tracing","authors":"Liujun Xu, Gaole Dai, Fubao Yang, Jinrong Liu, Yuhong Zhou, Jun Wang, Guoqiang Xu, Jiping Huang, Cheng-Wei Qiu","doi":"10.1038/s43588-024-00660-1","DOIUrl":"10.1038/s43588-024-00660-1","url":null,"abstract":"Transformation theory, active control and inverse design have been mainstream in creating free-form metamaterials. However, existing frameworks cannot simultaneously satisfy the requirements of isotropic, passive and forward design. Here we propose a forward conformality-assisted tracing method to address the geometric and single-physical-field constraints of conformal transformation. Using a conformal mesh composed of orthogonal streamlines and isotherms (or isothermal surfaces), this method quasi-analytically produces free-form metamaterials using only isotropic media. The geometric nature of this approach allows for universal regulation of both dissipative thermal fields and non-dissipative electromagnetic fields. We experimentally demonstrate free-form thermal cloaking in both two and three dimensions. Additionally, the multi-physical functionalities of our method, including optical cloaking, bending and thermo-electric transparency, confirm its broad applicability. Our method features improvements in efficiency, accuracy and adaptability over previous approaches. This study provides an effective method for designing complex metamaterials with arbitrary shapes across various physical domains. Here a conformality-assisted tracing method is proposed to devise free-form and three-dimensional conformal metamaterials, featuring accuracy and efficiency in handling complex geometry and adaptability to various diffusion and wave fields.","PeriodicalId":74246,"journal":{"name":"Nature computational science","volume":"4 7","pages":"532-541"},"PeriodicalIF":12.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1038/s43588-024-00650-3
Takahiro Yabe, Massimiliano Luca, Kota Tsubouchi, Bruno Lepri, Marta C. Gonzalez, Esteban Moro
Human mobility research intersects with various disciplines, with profound implications for urban planning, transportation engineering, public health, disaster management, and economic analysis. Here, we discuss the urgent need for open and standardized datasets in the field, including current challenges and lessons from other computational science domains, and propose collaborative efforts to enhance the validity and reproducibility of human mobility research.
{"title":"Enhancing human mobility research with open and standardized datasets","authors":"Takahiro Yabe, Massimiliano Luca, Kota Tsubouchi, Bruno Lepri, Marta C. Gonzalez, Esteban Moro","doi":"10.1038/s43588-024-00650-3","DOIUrl":"10.1038/s43588-024-00650-3","url":null,"abstract":"Human mobility research intersects with various disciplines, with profound implications for urban planning, transportation engineering, public health, disaster management, and economic analysis. Here, we discuss the urgent need for open and standardized datasets in the field, including current challenges and lessons from other computational science domains, and propose collaborative efforts to enhance the validity and reproducibility of human mobility research.","PeriodicalId":74246,"journal":{"name":"Nature computational science","volume":"4 7","pages":"469-472"},"PeriodicalIF":12.0,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43588-024-00650-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1038/s43588-024-00651-2
Alexandre Hocquet, Frédéric Wieber, Gabriele Gramelsberger, Konrad Hinsen, Markus Diesmann, Fernando Pasquini Santos, Catharina Landström, Benjamin Peters, Dawid Kasprowicz, Arianna Borrelli, Phillip Roth, Clarissa Ai Ling Lee, Alin Olteanu, Stefan Böschen
Software is much more than just code. It is time to confront the complexity of licenses, uses, governance, infrastructure and other facets of software in science. Their influence is ubiquitous yet overlooked.
{"title":"Software in science is ubiquitous yet overlooked","authors":"Alexandre Hocquet, Frédéric Wieber, Gabriele Gramelsberger, Konrad Hinsen, Markus Diesmann, Fernando Pasquini Santos, Catharina Landström, Benjamin Peters, Dawid Kasprowicz, Arianna Borrelli, Phillip Roth, Clarissa Ai Ling Lee, Alin Olteanu, Stefan Böschen","doi":"10.1038/s43588-024-00651-2","DOIUrl":"10.1038/s43588-024-00651-2","url":null,"abstract":"Software is much more than just code. It is time to confront the complexity of licenses, uses, governance, infrastructure and other facets of software in science. Their influence is ubiquitous yet overlooked.","PeriodicalId":74246,"journal":{"name":"Nature computational science","volume":"4 7","pages":"465-468"},"PeriodicalIF":12.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43588-024-00651-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28DOI: 10.1038/s43588-024-00643-2
Steven L. Brunton, J. Nathan Kutz
Partial differential equations (PDEs) are among the most universal and parsimonious descriptions of natural physical laws, capturing a rich variety of phenomenology and multiscale physics in a compact and symbolic representation. Here, we examine several promising avenues of PDE research that are being advanced by machine learning, including (1) discovering new governing PDEs and coarse-grained approximations for complex natural and engineered systems, (2) learning effective coordinate systems and reduced-order models to make PDEs more amenable to analysis, and (3) representing solution operators and improving traditional numerical algorithms. In each of these fields, we summarize key advances, ongoing challenges, and opportunities for further development. Machine learning has enabled major advances in the field of partial differential equations. This Review discusses some of these efforts and other ongoing challenges and opportunities for development.
{"title":"Promising directions of machine learning for partial differential equations","authors":"Steven L. Brunton, J. Nathan Kutz","doi":"10.1038/s43588-024-00643-2","DOIUrl":"10.1038/s43588-024-00643-2","url":null,"abstract":"Partial differential equations (PDEs) are among the most universal and parsimonious descriptions of natural physical laws, capturing a rich variety of phenomenology and multiscale physics in a compact and symbolic representation. Here, we examine several promising avenues of PDE research that are being advanced by machine learning, including (1) discovering new governing PDEs and coarse-grained approximations for complex natural and engineered systems, (2) learning effective coordinate systems and reduced-order models to make PDEs more amenable to analysis, and (3) representing solution operators and improving traditional numerical algorithms. In each of these fields, we summarize key advances, ongoing challenges, and opportunities for further development. Machine learning has enabled major advances in the field of partial differential equations. This Review discusses some of these efforts and other ongoing challenges and opportunities for development.","PeriodicalId":74246,"journal":{"name":"Nature computational science","volume":"4 7","pages":"483-494"},"PeriodicalIF":12.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-26DOI: 10.1038/s43588-024-00656-x
Nature Computational Science wants to publish your computational social science research.
自然-计算科学》希望发表您的计算社会科学研究成果。
{"title":"An invitation to social scientists","authors":"","doi":"10.1038/s43588-024-00656-x","DOIUrl":"10.1038/s43588-024-00656-x","url":null,"abstract":"Nature Computational Science wants to publish your computational social science research.","PeriodicalId":74246,"journal":{"name":"Nature computational science","volume":"4 6","pages":"381-381"},"PeriodicalIF":12.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s43588-024-00656-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1038/s43588-024-00637-0
Francisco Barreras, Duncan J. Watts
Large-scale GPS location datasets hold immense potential for measuring human mobility and interpersonal contact, both of which are essential for data-driven epidemiology. However, despite their potential and widespread adoption during the COVID-19 pandemic, there are several challenges with these data that raise concerns regarding the validity and robustness of its applications. Here we outline two types of challenges—some related to accessing and processing these data, and some related to data quality—and propose several research directions to address them moving forward. While large-scale GPS location datasets have been instrumental to applications in epidemiology, there are still several challenges with these data that should be considered and addressed to make data-driven epidemiology more reliable.
{"title":"The exciting potential and daunting challenge of using GPS human-mobility data for epidemic modeling","authors":"Francisco Barreras, Duncan J. Watts","doi":"10.1038/s43588-024-00637-0","DOIUrl":"10.1038/s43588-024-00637-0","url":null,"abstract":"Large-scale GPS location datasets hold immense potential for measuring human mobility and interpersonal contact, both of which are essential for data-driven epidemiology. However, despite their potential and widespread adoption during the COVID-19 pandemic, there are several challenges with these data that raise concerns regarding the validity and robustness of its applications. Here we outline two types of challenges—some related to accessing and processing these data, and some related to data quality—and propose several research directions to address them moving forward. While large-scale GPS location datasets have been instrumental to applications in epidemiology, there are still several challenges with these data that should be considered and addressed to make data-driven epidemiology more reliable.","PeriodicalId":74246,"journal":{"name":"Nature computational science","volume":"4 6","pages":"398-411"},"PeriodicalIF":12.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-17DOI: 10.1038/s43588-024-00639-y
Jenna C. Fromer, Connor W. Coley
Small molecules exhibiting desirable property profiles are often discovered through an iterative process of designing, synthesizing and testing sets of molecules. The selection of molecules to synthesize from all possible candidates is a complex decision-making process that typically relies on expert chemist intuition. Here we propose a quantitative decision-making framework, SPARROW, that prioritizes molecules for evaluation by balancing expected information gain and synthetic cost. SPARROW integrates molecular design, property prediction and retrosynthetic planning to balance the utility of testing a molecule with the cost of batch synthesis. We demonstrate, through three case studies, that the developed algorithm captures the non-additive costs inherent to batch synthesis, leverages common reaction steps and intermediates, and scales to hundreds of molecules. The downselection of compounds for synthesis is a key challenge in molecular design cycles that typically relies on expert chemist intuition. Fromer and Coley propose a cost-aware method to automatically select compounds and synthetic routes.
{"title":"An algorithmic framework for synthetic cost-aware decision making in molecular design","authors":"Jenna C. Fromer, Connor W. Coley","doi":"10.1038/s43588-024-00639-y","DOIUrl":"10.1038/s43588-024-00639-y","url":null,"abstract":"Small molecules exhibiting desirable property profiles are often discovered through an iterative process of designing, synthesizing and testing sets of molecules. The selection of molecules to synthesize from all possible candidates is a complex decision-making process that typically relies on expert chemist intuition. Here we propose a quantitative decision-making framework, SPARROW, that prioritizes molecules for evaluation by balancing expected information gain and synthetic cost. SPARROW integrates molecular design, property prediction and retrosynthetic planning to balance the utility of testing a molecule with the cost of batch synthesis. We demonstrate, through three case studies, that the developed algorithm captures the non-additive costs inherent to batch synthesis, leverages common reaction steps and intermediates, and scales to hundreds of molecules. The downselection of compounds for synthesis is a key challenge in molecular design cycles that typically relies on expert chemist intuition. Fromer and Coley propose a cost-aware method to automatically select compounds and synthetic routes.","PeriodicalId":74246,"journal":{"name":"Nature computational science","volume":"4 6","pages":"440-450"},"PeriodicalIF":12.0,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141422123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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