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Article ; Online: Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process.

Shan, Ke-Jia / Wei, Changshuo / Wang, Yu / Huan, Qing / Qian, Wenfeng

Innovation (Cambridge (Mass.))

2021 Volume 2, Issue 4, Page(s) 100159

Abstract: The capacity of RNA viruses to adapt to new hosts and rapidly escape the host immune system is largely attributable ... ...

Abstract	The capacity of RNA viruses to adapt to new hosts and rapidly escape the host immune system is largely attributable to
Language	English
Publishing date	2021-08-30
Publishing country	United States
Document type	Journal Article
ISSN	2666-6758
ISSN (online)	2666-6758
DOI	10.1016/j.xinn.2021.100159
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Missing Expression Level-Evolutionary Rate Anticorrelation in Viruses Does Not Support Protein Function as a Main Constraint on Sequence Evolution.

Wei, Changshuo / Chen, Yan-Ming / Chen, Ying / Qian, Wenfeng

Genome biology and evolution

2021 Volume 13, Issue 4

Abstract: One of the central goals in molecular evolutionary biology is to determine the sources of variation in the rate of sequence evolution among proteins. Gene expression level is widely accepted as the primary determinant of protein evolutionary rate, ... ...

Abstract	One of the central goals in molecular evolutionary biology is to determine the sources of variation in the rate of sequence evolution among proteins. Gene expression level is widely accepted as the primary determinant of protein evolutionary rate, because it scales with the extent of selective constraints imposed on a protein, leading to the well-known negative correlation between expression level and protein evolutionary rate (the E-R anticorrelation). Selective constraints have been hypothesized to entail the maintenance of protein function, the avoidance of cytotoxicity caused by protein misfolding or nonspecific protein-protein interactions, or both. However, empirical tests evaluating the relative importance of these hypotheses remain scarce, likely due to the nontrivial difficulties in distinguishing the effect of a deleterious mutation on a protein's function versus its cytotoxicity. We realized that examining the sequence evolution of viral proteins could overcome this hurdle. It is because purifying selection against mutations in a viral protein that result in cytotoxicity per se is likely relaxed, whereas purifying selection against mutations that impair viral protein function persists. Multiple analyses of SARS-CoV-2 and nine other virus species revealed a complete absence of any E-R anticorrelation. As a control, the E-R anticorrelation does exist in human endogenous retroviruses where purifying selection against cytotoxicity is present. Taken together, these observations do not support the maintenance of protein function as the main constraint on protein sequence evolution in cellular organisms.
MeSH term(s)	Amino Acid Sequence ; Animals ; Endogenous Retroviruses/genetics ; Evolution, Molecular ; Humans ; Middle East Respiratory Syndrome Coronavirus/genetics ; Mutation ; SARS-CoV-2/genetics ; Sequence Analysis, RNA ; Viral Proteins/genetics
Chemical Substances	Viral Proteins
Language	English
Publishing date	2021-03-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2495328-3
ISSN	1759-6653 ; 1759-6653
ISSN (online)	1759-6653
ISSN	1759-6653
DOI	10.1093/gbe/evab049
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Book ; Online: Toward Cohort Intelligence

Liu, Changshuo / Zhang, Wenqiao / Ooi, Beng Chin / Yip, James Wei Luen / Zeng, Lingze / Zheng, Kaiping

A Universal Cohort Representation Learning Framework for Electronic Health Record Analysis

2023

Abstract: Electronic Health Records (EHR) are generated from clinical routine care recording valuable information of broad patient populations, which provide plentiful opportunities for improving patient management and intervention strategies in clinical practice. ...

Abstract	Electronic Health Records (EHR) are generated from clinical routine care recording valuable information of broad patient populations, which provide plentiful opportunities for improving patient management and intervention strategies in clinical practice. To exploit the enormous potential of EHR data, a popular EHR data analysis paradigm in machine learning is EHR representation learning, which first leverages the individual patient's EHR data to learn informative representations by a backbone, and supports diverse health-care downstream tasks grounded on the representations. Unfortunately, such a paradigm fails to access the in-depth analysis of patients' relevance, which is generally known as cohort studies in clinical practice. Specifically, patients in the same cohort tend to share similar characteristics, implying their resemblance in medical conditions such as symptoms or diseases. In this paper, we propose a universal COhort Representation lEarning (CORE) framework to augment EHR utilization by leveraging the fine-grained cohort information among patients. In particular, CORE first develops an explicit patient modeling task based on the prior knowledge of patients' diagnosis codes, which measures the latent relevance among patients to adaptively divide the cohorts for each patient. Based on the constructed cohorts, CORE recodes the pre-extracted EHR data representation from intra- and inter-cohort perspectives, yielding augmented EHR data representation learning. CORE is readily applicable to diverse backbone models, serving as a universal plug-in framework to infuse cohort information into healthcare methods for boosted performance. We conduct an extensive experimental evaluation on two real-world datasets, and the experimental results demonstrate the effectiveness and generalizability of CORE. Comment: 10 pages
Keywords	Computer Science - Machine Learning ; Computer Science - Artificial Intelligence
Subject code	006
Publishing date	2023-04-10
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Host-specific asymmetric accumulation of mutation types reveals that the origin of SARS-CoV-2 is consistent with a natural process

Ke-Jia Shan / Changshuo Wei / Yu Wang / Qing Huan / Wenfeng Qian

The Innovation, Vol 2, Iss 4, Pp 100159- (2021)

2021

Abstract: The capacity of RNA viruses to adapt to new hosts and rapidly escape the host immune system is largely attributable to de novo genetic diversity that emerges through mutations in RNA. Although the molecular spectrum of de novo mutations—the relative ... ...

Abstract	The capacity of RNA viruses to adapt to new hosts and rapidly escape the host immune system is largely attributable to de novo genetic diversity that emerges through mutations in RNA. Although the molecular spectrum of de novo mutations—the relative rates at which various base substitutions occur—are widely recognized as informative toward understanding the evolution of a viral genome, little attention has been paid to the possibility of using molecular spectra to infer the host origins of a virus. Here, we characterize the molecular spectrum of de novo mutations for SARS-CoV-2 from transcriptomic data obtained from virus-infected cell lines, enabled by the use of sporadic junctions formed during discontinuous transcription as molecular barcodes. We find that de novo mutations are generated in a replication-independent manner, typically on the genomic strand, and highly dependent on mutagenic mechanisms specific to the host cellular environment. De novo mutations will then strongly influence the types of base substitutions accumulated during SARS-CoV-2 evolution, in an asymmetric manner favoring specific mutation types. Consequently, similarities between the mutation spectra of SARS-CoV-2 and the bat coronavirus RaTG13, which have accumulated since their divergence strongly suggest that SARS-CoV-2 evolved in a host cellular environment highly similar to that of bats before its zoonotic transfer into humans. Collectively, our findings provide data-driven support for the natural origin of SARS-CoV-2. Public summary: • The asymmetric de novo mutations in SARS-CoV-2 are induced by mutagenic mechanisms in the host cellular environment • De novo mutations determine the molecular spectrum of accumulated mutations during SARS-CoV-2 evolution • Molecular spectra of accumulated mutations in betacoronaviruses cluster according to the host species instead of the phylogenetic relationship • The mutations accumulated in SARS-CoV-2 prior to its transmission to humans are consistent with an evolutionary process in a bat host
Keywords	SARS-CoV-2 ; molecular spectrum ; de novo mutations ; mutational signature ; evolutionary origin ; mRNA mutation ; Science (General) ; Q1-390
Subject code	616
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Evidence for a mouse origin of the SARS-CoV-2 Omicron variant

Wei, Changshuo / Shan, Ke-Jia / Wang, Weiguang / Zhang, Shuya / Huan, Qing / Qian, Wenfeng

Journal of genetics and genomics. 2021 Dec., v. 48, no. 12

2021

Abstract: The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 point mutations that Omicron acquired ... ...

Abstract	The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage. We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting a possibility of host-jumping. The molecular spectrum of mutations (i.e., the relative frequency of the 12 types of base substitutions) acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients but resembled the spectra associated with virus evolution in a mouse cellular environment. Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor. Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak.
Keywords	Severe acute respiratory syndrome coronavirus 2 ; amino acid sequences ; evolution ; genomics ; humans ; mice ; viruses
Language	English
Dates of publication	2021-12
Size	p. 1111-1121.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2374568-X
ISSN	1873-5533 ; 1673-8527
ISSN (online)	1873-5533
ISSN	1673-8527
DOI	10.1016/j.jgg.2021.12.003
Database	NAL-Catalogue (AGRICOLA)

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Article: Evidence for a mouse origin of the SARS-CoV-2 Omicron variant.

Wei, Changshuo / Shan, Ke-Jia / Wang, Weiguang / Zhang, Shuya / Huan, Qing / Qian, Wenfeng

Journal of genetics and genomics = Yi chuan xue bao

2021 Volume 48, Issue 12, Page(s) 1111–1121

Abstract	The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage. We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting a possibility of host-jumping. The molecular spectrum of mutations (i.e., the relative frequency of the 12 types of base substitutions) acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients but resembled the spectra associated with virus evolution in a mouse cellular environment. Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor. Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak.
MeSH term(s)	Animals ; Binding Sites ; COVID-19/genetics ; COVID-19/virology ; Evolution, Molecular ; Host Specificity/genetics ; Host-Pathogen Interactions/genetics ; Humans ; Mice ; Mutation/genetics ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; Spike Glycoprotein, Coronavirus/genetics
Chemical Substances	Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2021-12-24
Publishing country	China
Document type	Journal Article
ZDB-ID	2374568-X
ISSN	1873-5533 ; 1673-8527
ISSN (online)	1873-5533
ISSN	1673-8527
DOI	10.1016/j.jgg.2021.12.003
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Article ; Online: The memory of neuronal mitochondrial stress is inherited transgenerationally via elevated mitochondrial DNA levels.

Zhang, Qian / Wang, Zihao / Zhang, Wenfeng / Wen, Qingbo / Li, Xinyu / Zhou, Jun / Wu, Xueying / Guo, Yongqing / Liu, Yangli / Wei, Changshuo / Qian, Wenfeng / Tian, Ye

Nature cell biology

2021 Volume 23, Issue 8, Page(s) 870–880

Abstract: The memory of stresses experienced by parents can be passed on to descendants as a forecast of the challenges to come. Here, we discovered that the neuronal mitochondrial perturbation-induced systemic mitochondrial unfolded protein response ( ... ...

Abstract	The memory of stresses experienced by parents can be passed on to descendants as a forecast of the challenges to come. Here, we discovered that the neuronal mitochondrial perturbation-induced systemic mitochondrial unfolded protein response (UPR
MeSH term(s)	Caenorhabditis elegans Proteins/genetics ; DNA, Mitochondrial/metabolism ; Genes, Mitochondrial ; HEK293 Cells ; Humans ; Longevity/genetics ; Maternal Inheritance ; Neurons/metabolism ; Organelle Biogenesis ; Stress, Physiological/genetics ; Unfolded Protein Response/genetics ; Wnt Signaling Pathway
Chemical Substances	Caenorhabditis elegans Proteins ; DNA, Mitochondrial
Language	English
Publishing date	2021-08-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1474722-4
ISSN	1476-4679 ; 1465-7392
ISSN (online)	1476-4679
ISSN	1465-7392
DOI	10.1038/s41556-021-00724-8
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Article ; Online: Evidence for a mouse origin of the SARS-CoV-2 Omicron variant

Wei, Changshuo / Shan, Ke-Jia / Wang, Weiguang / Zhang, Shuya / Huan, Qing / Qian, Wenfeng

bioRxiv

Abstract	The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage. We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting the possibility of host-jumping. The molecular spectrum (i.e., the relative frequency of the twelve types of base substitutions) of mutations acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients, but was highly consistent with spectra associated with evolution in a mouse cellular environment. Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor. Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak.
Keywords	covid19
Language	English
Publishing date	2021-12-15
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.12.14.472632
Database	COVID19

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Book ; Online: From Plate to Prevention

Zheng, Kaiping / Nguyen, Thao / Chong, Jesslyn Hwei Sing / Goh, Charlene Enhui / Herschel, Melanie / Lee, Hee Hoon / Liu, Changshuo / Ooi, Beng Chin / Wang, Wei / Yip, James

A Dietary Nutrient-aided Platform for Health Promotion in Singapore

2023

Abstract: Singapore has been striving to improve the provision of healthcare services to her people. In this course, the government has taken note of the deficiency in regulating and supervising people's nutrient intake, which is identified as a contributing ... ...

Abstract	Singapore has been striving to improve the provision of healthcare services to her people. In this course, the government has taken note of the deficiency in regulating and supervising people's nutrient intake, which is identified as a contributing factor to the development of chronic diseases. Consequently, this issue has garnered significant attention. In this paper, we share our experience in addressing this issue and attaining medical-grade nutrient intake information to benefit Singaporeans in different aspects. To this end, we develop the FoodSG platform to incubate diverse healthcare-oriented applications as a service in Singapore, taking into account their shared requirements. We further identify the profound meaning of localized food datasets and systematically clean and curate a localized Singaporean food dataset FoodSG-233. To overcome the hurdle in recognition performance brought by Singaporean multifarious food dishes, we propose to integrate supervised contrastive learning into our food recognition model FoodSG-SCL for the intrinsic capability to mine hard positive/negative samples and therefore boost the accuracy. Through a comprehensive evaluation, we present performance results of the proposed model and insights on food-related healthcare applications. The FoodSG-233 dataset has been released in https://foodlg.comp.nus.edu.sg/.
Keywords	Computer Science - Machine Learning ; Computer Science - Artificial Intelligence ; Computer Science - Computer Vision and Pattern Recognition ; Computer Science - Databases ; Computer Science - Multimedia
Subject code	006
Publishing date	2023-01-10
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The Ghd7 transcription factor represses ARE1 expression to enhance nitrogen utilization and grain yield in rice

Wang, Qing / Su, Qingmei / Nian, Jinqiang / Zhang, Jian / Guo, Meng / Dong, Guojun / Hu, Jiang / Wang, Rongsheng / Wei, Changshuo / Li, Guanwen / Wang, Wan / Guo, Hui-Shan / Lin, Shaoyang / Qian, Wenfeng / Xie, Xianzhi / Qian, Qian / Chen, Fan / Zuo, Jianru

Molecular plant. 2021 June 07, v. 14, no. 6

2021

Abstract: The genetic improvement of nitrogen use efficiency (NUE) of crops is vital for grain productivity and sustainable agriculture. However, the regulatory mechanism of NUE remains largely elusive. Here, we report that the rice Grain number, plant height, and ...

Abstract	The genetic improvement of nitrogen use efficiency (NUE) of crops is vital for grain productivity and sustainable agriculture. However, the regulatory mechanism of NUE remains largely elusive. Here, we report that the rice Grain number, plant height, and heading date7 (Ghd7) gene genetically acts upstream of ABC1 REPRESSOR1 (ARE1), a negative regulator of NUE, to positively regulate nitrogen utilization. As a transcriptional repressor, Ghd7 directly binds to two Evening Element-like motifs in the promoter and intron 1 of ARE1, likely in a cooperative manner, to repress its expression. Ghd7 and ARE1 display diurnal expression patterns in an inverse oscillation manner, mirroring a regulatory scheme based on these two loci. Analysis of a panel of 2656 rice varieties suggests that the elite alleles of Ghd7 and ARE1 have undergone diversifying selection during breeding. Moreover, the allelic distribution of Ghd7 and ARE1 is associated with the soil nitrogen deposition rate in East Asia and South Asia. Remarkably, the combination of the Ghd7 and ARE1 elite alleles substantially improves NUE and yield performance under nitrogen-limiting conditions. Collectively, these results define a Ghd7–ARE1-based regulatory mechanism of nitrogen utilization, providing useful targets for genetic improvement of rice NUE.
Keywords	genetic improvement ; grain yield ; introns ; nitrogen ; nutrient use efficiency ; plant height ; repressor proteins ; rice ; soil ; sustainable agriculture ; East Asia ; South Asia
Language	English
Dates of publication	2021-0607
Size	p. 1012-1023.
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	2393618-6
ISSN	1752-9867 ; 1674-2052
ISSN (online)	1752-9867
ISSN	1674-2052
DOI	10.1016/j.molp.2021.04.012
Database	NAL-Catalogue (AGRICOLA)

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