（Phenomics期刊2023年第五期封面图）

01 Mycobacteriaceae Phenome Atlas (MPA): A Standardized Atlas for the Mycobacteriaceae Phenome Based on Heterogeneous Sources

MPA的开发方法图解

DOI：https://doi.org/10.1007/s43657-023-00101-5

引用格式：Liu, W., Cen, H., Wu, Z. et al. Mycobacteriaceae Phenome Atlas (MPA): A Standardized Atlas for the Mycobacteriaceae Phenome Based on Heterogeneous Sources. Phenomics (2023). https://doi.org/10.1007/s43657-023-00101-5

该研究采用数据驱动的方法建立了分枝杆菌科表型组的数据元素集，这是对现有微生物表型数据元素集的一个宝贵补充。通过使用分枝杆菌科表型组，该团队构建了最大、最完整的分枝杆菌科数据集，该数据集的应用将对分枝杆菌科的致病机制和抗菌研究提供新的视角。

AbstractThe bacterial family Mycobacteriaceae includes pathogenic and nonpathogenic bacteria, and systematic research on their genome and phenome can give comprehensive perspectives for exploring their disease mechanism. In this study, the phenotypes of Mycobacteriaceae were inferred from available phenomic data, and 82 microbial phenotypic traits were recruited as data elements of the microbial phenome. This Mycobacteriaceae phenome contains five categories and 20 subcategories of polyphasic phenotypes, and three categories and eight subcategories of functional phenotypes, all of which are complementary to the existing data standards of microbial phenotypes. The phenomic data of Mycobacteriaceae strains were compiled by literature mining, third-party database integration, and bioinformatics annotation. The phenotypes were searchable and comparable from the website of the Mycobacteriaceae Phenome Atlas (MPA, https://www.biosino.org/mpa/). A topological data analysis of MPA revealed the co-evolution between Mycobacterium tuberculosis and virulence factors, and uncovered potential pathogenicity-associated phenotypes. Two hundred and sixty potential pathogen-enriched pathways were found by Fisher's exact test. The application of MPA may provide novel insights into the pathogenicity mechanism and antimicrobial targets of Mycobacteriaceae.

02 α2,3-Sialylation with Fucosylation Associated with More Severe Anti-MDA5 Positive Dermatomyositis Induced by Rapidly Progressive Interstitial Lung Disease

N-糖组定量分析的简要工作流程及具有代表性的糖链结构组成

DOI：https://doi.org/10.1007/s43657-023-00096-z

引用格式：Zhang, R., Guo, L., Sha, J. et al. α2,3-Sialylation with Fucosylation Associated with More Severe Anti-MDA5 Positive Dermatomyositis Induced by Rapidly Progressive Interstitial Lung Disease. Phenomics 3, 457–468 (2023). https://doi.org/10.1007/s43657-023-00096-z

该研究中，作者研究了血浆全糖组与皮肌炎，尤其是MDA5+DM-RPILD之间的关联，揭示DM相关N-糖基化表型特征，并考察了其作为MDA5+DM诊断和预后标志物的潜力。

AbstractDermatomyositis (DM) is a heterogeneous autoimmune disease associated with numerous myositis specifc antibodies (MSAs) in which DM with anti-melanoma diferentiation-associated gene 5-positive (MDA5+DM) is a unique subtype of DM with higher risk of developing varying degrees of Interstitial lung disease (ILD). Glycosylation is a complex posttranslational modifcation of proteins associated with many autoimmune diseases. However, the association of total plasma N-glycome (TPNG) and DM, especially MDA5+DM, is still unknown. TPNG of 94 DM patients and 168 controls were analyzed by mass spectrometry with in-house reliable quantitative method called Bionic Glycome method. Logistic regression with age and sex adjusted was used to reveal the aberrant glycosylation of DM and the association of TPNG and MDA5+DM with or without rapidly progressive ILD (RPILD). The elastic net model was used to evaluate performance of glycans in distinguishing RPLID from non-RPILD, and survival analysis was analyzed with N-glycoslyation score by Kaplan–Meier survival analysis. It was found that the plasma protein N-glycome in DM showed higher fucosylation and bisection, lower sialylation (α2,3- not α2,6-linked) and galactosylation than controls. In MDA5+DM, more severe disease condition was associated with decreased sialylation (specifcally α2,3-sialylation with fucosylation) while accompanying elevated H6N5S3 and H5N4FSx, decreased galactosylation and increased fucosylation and the complexity of N-glycans. Moreover, glycosylation traits have better discrimination ability to distinguish RPILD from non-RPILD with AUC 0.922 than clinical features and is MDA5-independent. Survival advantage accrued to MDA5+DM with lower N-glycosylation score (p=3e-04). Our study reveals the aberrant glycosylation of DM for the frst time and indicated that glycosylation is associated with disease severity caused by ILD in MDA5+DM, which might be considered as the potential biomarker for early diagnosis of RPILD and survival evaluation of MDA5+DM.

03 Auxiliary Diagnosis of Papillary Thyroid Carcinoma Based on Spectral Phenotype

自建光谱采集装置

DOI：https://doi.org/10.1007/s43657-023-00113-1

引用格式：Zhao, B., Wang, Y., Hu, M. et al. Auxiliary Diagnosis of Papillary Thyroid Carcinoma Based on Spectral Phenotype. Phenomics (2023). https://doi.org/10.1007/s43657-023-00113-1

该研究通过光谱数据结合特征空间优化方法构建甲状腺乳头状癌(Papillary Thyroid Carcinoma，PTC)分类模型，计算竞争自适应重加权抽样 (Competitive Adapative Reweighted Sampling，CARS)算法提取得到甲状腺特征光谱与临床、图像指标的相关性，解释特征光谱在筛选范围内与氨基酸分子存在的映射关系，从光谱表型角度为甲状腺乳头状癌的可解释模型提供新的依据与见解。

AbstractThyroid cancer, a common endocrine malignancy, is one of the leading death causes among endocrine tumors. The diagnosis of pathological section analysis suffers from diagnostic delay and cumbersome operating procedures. Therefore, we intend to construct the models based on spectral data that can be potentially used for rapid intraoperative papillary thyroid carcinoma (PTC) diagnosis and characterize PTC characteristics. To alleviate any concerns pathologists may have about using the model, we conducted an analysis of the used bands that can be interpreted pathologically. A spectra acquisition system was first built to acquire spectra of pathological section images from 91 patients. The obtained spectral dataset contains 217 spectra of normal thyroid tissue and 217 spectra of PTC tissue. Clinical data of the corresponding patients were collected for subsequent model interpretability analysis. The experiment has been approved by the Ethics Review Committee of the Wuhu Hospital of East China Normal University. The spectral preprocessing method was used to process the spectra, and the preprocessed signal respectively optimized by the first and secondary informative wavelengths selection was used to develop the PTC detection models. The PTC detection model using mean centering (MC) and multiple scattering correction (MSC) has optimal performance, and the reasons for the good performance were analyzed in combination with the spectral acquisition process and composition of the test slide. For model interpretable analysis, the near-ultraviolet band selected for modeling corresponds to the location of amino acid absorption peak, and this is consistent with the clinical phenomenon of significantly lower amino acid concentrations in PTC patients. Moreover, the absorption peak of hemoglobin selected for modeling is consistent with the low hemoglobin index in PTC patients. In addition, the correlation analysis was performed between the selected wavelengths and the clinical data, and the results show: the reflection intensity of selected wavelengths in normal cells has a moderate correlation with cell arrangement structure, nucleus size and free thyroxine (FT4), and has a strong correlation with triiodothyronine (T3); the reflection intensity of selected bands in PTC cells has a moderate correlation with free triiodothyronine (FT3).04 A Common Functional Variant at the Enhancer of the Rheumatoid Arthritis Risk Gene ORMDL3 Regulates its Expression Through Allele-Specific JunD Binding

通过整合多“组学”数据的基因组分析发现类风湿关节炎风险基因及其潜在的增强子调控区域

DOI：https://doi.org/10.1007/s43657-023-00107-z

引用格式：Ye, W., Yu, Y., Zhu, X. et al. A Common Functional Variant at the Enhancer of the Rheumatoid Arthritis Risk Gene ORMDL3 Regulates its Expression Through Allele-Specific JunD Binding. Phenomics (2023). https://doi.org/10.1007/s43657-023-00107-z

该研究研究通过整合多个“组学”数据的综合基因组分析，发现潜在类风湿关节炎风险基因 ORMDL3 及其增强子调控区域， 并通过体内外实验验证了该区域的 rs56199421 的 T 等位基因可以增强转录因子 JunD 与其结合，导致 ORMDL3 表达升高和类风湿关节炎发病的增加。

AbstractGenome-wide association studies (GWASs) have identified over 100 loci associated with rheumatoid arthritis (RA); however, the functionally affected genes and the underlying molecular mechanisms contributing to these associations are often unknown. In this study, we conducted an integrative genomic analysis incorporating multiple “omics” data and identified a functional regulatory DNA variant, rs56199421, and a plausible mechanism by which it regulates the expression of a putative RA risk gene, ORMDL Sphingolipid Biosynthesis Regulator 3 (ORMDL3). The T allele of rs56199421, located in the enhancer region of ORMDL3, exhibited stronger direct binding ability than the other C allele of rs56199421 did in vitro with the transcription factor JunD and demonstrated higher transcriptional activity. Moreover, the T allele of rs56199421 is associated with elevated RA risk, and ORMDL3 expression is increased in RA patients. Thus, these findings suggest that the T allele of rs56199421 enhances JunD transcription factor binding, increases enhancer activity, and elevates the expression of the RA risk gene ORMDL3.

05 Inflammation as a Mediator of Microbiome Dysbiosis-Associated DNA Methylation Changes in Gastric Premalignant Lesions

胃菌群失调与PLGC和DNA甲基化改变的风险相关

DOI：https://link.springer.com/article/10.1007/s43657-023-00118-w

引用格式：Yan, L., Li, W., Chen, F. et al. Inflammation as a Mediator of Microbiome Dysbiosis-Associated DNA Methylation Changes in Gastric Premalignant Lesions. Phenomics (2023). https://doi.org/10.1007/s43657-023-00118-w

慢性萎缩性胃炎(Chronic atrophic gastritis, CAG)、肠化生(Intestinal metaplasia, IM)和异型增生(Dysplasia, DYS) 被认为是胃癌的癌前病变阶段。既往研究表明，胃微生物群失调与PLGC以及胃癌的发生发展密切相关，但其潜在机制尚未完全阐明。持续性慢性炎症是胃微生物群失调最重要的致病机制之一。此外，一些研究证据发现炎症反应与异常DNA甲基化相关。因此，该文研究者推测炎症可能在胃菌群失调和DNA甲基化改变的关联间发挥中介作用。而这项基于人群的研究便旨在评估胃微生物组与PLGC发生过程中DNA甲基化改变之间的关系，并探讨炎症反应在这一关系中的中介作用。

AbstractEvidence for the influence of chronic inflammation induced by microbial dysbiosis on aberrant DNA methylation supports a plausible connexion between disordered microbiota and precancerous lesions of gastric cancer (PLGC). Here, a comprehensive study including multi-omics data was performed to estimate the relationships amongst the gastric microbiome, inflammatory proteins and DNA methylation alterations and their roles in PLGC development. The results demonstrated that gastric dysbacteriosis increased the risk of PLGC and DNA methylation alterations in related tumour suppressor genes. Seven inflammatory biomarkers were identified for antrum and corpus tissues, respectively, amongst which the expression levels of several biomarkers were significantly correlated with the microbial dysbiosis index (MDI) and methylation status of specific tumour suppressor genes. Notably, mediation analysis revealed that microbial dysbiosis partially contributed to DNA methylation changes in the stomach via the inflammatory cytokines C–C motif chemokine 20 (CCL20) and tumour necrosis factor receptor superfamily member 9 (TNFRSF9). Overall, these results may provide new insights into the mechanisms that might link the gastric microbiome to PLGC.06 Infrared Imageries of Human Body Activated by Tea Match the Hypothesis of Meridian System

志愿者 M0 喝下 12 种茶水后的红外图像，这些茶水流入中医 12 条经脉

DOI：https://doi.org/10.1007/s43657-022-00090-x

引用格式：Jin, W., Tao, Y., Wang, C. et al. Infrared Imageries of Human Body Activated by Tea Match the Hypothesis of Meridian System. Phenomics 3, 502–518 (2023). https://doi.org/10.1007/s43657-022-00090-x

该研究从草药中挑选了 13 种茶叶，以激活假设的 12 条经脉，从而达到意象摄取的目的。42 名志愿者参加了为期 13 天的实验。不同的茶在不同天数进行测试。每次饮茶后，立即对人体进行红外线成像。从图像中得出并分析了手指、手掌和器官上方的最高温度。根据经络假说，可能由 12 条假说经络连接的器官和手指的温度一起显著上升。红外图像显示了不同茶叶激活器官的清晰形状，如黄茶激活心脏和肾脏等。一些高温线也与假设的经络相吻合。该工作首次展示了全部 12 条假说经络的可能图像，并用数据证明了不同的食物可能按照经络假说激活不同的器官，为靶向药物设计提供了一种可能的新方法。根据这种激活方法，可以开发出经络表型的测量方法。

AbstractHuman meridian (Jingluo) system was hypothesized by traditional Chinese medicine (TCM) for thousands of years, suggesting 12 normal meridian channels going through respective organs, carrying fluid and energy, and laying thermal effects. Some treatments based on meridians have been proved effective. However, existence of meridians has never been confirmed, let alone the lack of measurement for meridian phenotypes. Thermal effect is one of the major phenotypes of meridian metabolism. Infrared photograph was employed to display the picture of meridians since 1970. Unfortunately, no satisfactory results have been obtained. It is possible that only when a certain meridian is activated will there be thermal effect for successful infrared photograph. In this study, 13 types of tea were selected out of the herbs to activate the hypothesized 12 meridians for imagery taking. Forty-two volunteers took part in the experiment lasted for 13 days. Different tea was tested in different day. Infrared imageries of the human bodies were taken immediately after each tea was drunk. The highest temperatures of the fingers, palms, and above the organs were derived from the imageries and analyzed. The temperatures of the organs and fingers possibly connected by 12 hypothesized meridians rose together significantly following the meridian hypothesis. Infrared imageries showed quite clear shapes of the organs activated by different kinds of tea, e.g., heart and kidneys by yellow tea, etc. Some high temperature lines also matched the hypothetic meridians. Our work displayed the probable imageries of all the 12 hypothetic meridians for the first time, and proved with data that different foods may activate different organs following the meridian hypothesis, shedding light on a possible new method of targeted drug designs. Measurements of meridian phenotypes can be developed based on this method of activation.07 A Protocol for Digitalized Collection of Traditional Chinese Medicine (TCM) Pulse Information Using Bionic Pulse Diagnosis Equipment

中医理论中的视觉定位

DOI：https://doi.org/10.1007/s43657-023-00104-2

引用格式：Zhu, X., Wang, F., Mao, J. et al. A Protocol for Digitalized Collection of Traditional Chinese Medicine (TCM) Pulse Information Using Bionic Pulse Diagnosis Equipment. Phenomics 3, 519–534 (2023). https://doi.org/10.1007/s43657-023-00104-2

该研究提出了一种基于仿生脉诊设备的数字化中医脉诊信息采集方案，该方案可确保脉诊信息的高效性、可靠性和数据完整性。该方案的实施有利于促进脉象信息数字化采集的规范化，提高异常健康状态检测的有效性，推动中医脉象表型学等中医基础与临床研究。

AbstractPulse diagnosis equipment used in Traditional Chinese Medicine (TCM) has long been developed for collecting pulse information and in TCM research. However, it is still difficult to implement pulse taking automatically or efficiently in clinical practice. Here, we present a digital protocol for TCM pulse information collection based on bionic pulse diagnosis equipment, which ensures high efficiency, reliability and data integrity of pulse diagnosis information. A four-degree-of-freedom pulse taking platform together with a wrist bracket can satisfy the spatial positioning and angle requirements for individually adaptive pulse acquisition. Three-dimensional reconstruction of a wrist surface and an image localization model are combined to provide coordinates of the acquisition position and detection direction automatically. Three series elastic joints can not only simulate the TCM pulse taking method that “Three fingers in a straight line, the middle finger determining the ‘Guan’ location and finger pulp pressing on the radial artery,” but also simultaneously carry out the force-controlled multi-gradient pressing process. In terms of pulse information integrity, this proposed protocol can generate rich pulse information, including basic individual information, pulse localization distribution, multi-gradient dynamic pulse force time series, and objective pulse parameters, which can help establish the fundamental data sets that are required as the pulse phenotype for subsequent comprehensive analysis of pulse diagnosis. The implementation of this scheme is beneficial to promote the standardization of the digitalized collection of pulse information, the effectiveness of detecting abnormal health status, and the promotion of the fundamental and clinical research of TCM, such as TCM pulse phenomics.

08 Oral Microbiota: A New Insight into Cancer Progression, Diagnosis and Treatment

环境因素、口腔微生物群、口腔微环境和宿主健康之间的关系

DOI：https://doi.org/10.1007/s43657-023-00124-y

引用格式：Wang, XL., Xu, HW. & Liu, NN. Oral Microbiota: A New Insight into Cancer Progression, Diagnosis and Treatment. Phenomics 3, 535–547 (2023). https://doi.org/10.1007/s43657-023-00124-y

该综述主要关注以下几个方面：（1）影响口腔微生物群组成和功能的因素；（2）微环境与口腔微生物群之间的相互作用；（3）多菌群口腔微生物群在人类健康中的作用；（4）口腔微生物群抗癌的潜在机制和治疗作用。最后，该综述旨在描述口腔微生物群对癌症进展的影响，并为针对口腔微生物群的癌症预防和治疗提供新的治疗见解。

AbstractThe polymorphic microbiome has been defined as one of the “Hallmarks of Cancer”. Extensive studies have now uncovered the role of oral microbiota in cancer development and progression. Bacteria, fungi, archaea, and viruses in the oral cavity interact dynamically with the oral microenvironment to maintain the oral micro-ecological homeostasis. This complex interaction is influenced by many factors, such as maternal transmission, personal factors and environmental factors. Dysbiosis of oral microbiota can disturbed this host–microbiota interaction, leading to systemic diseases. Numerous studies have shown the potential associations between oral microbiota and a variety of cancers. However, the underlying mechanisms and therapeutic insights are still poorly understood. In this review, we mainly focus on the following aspects: (1) the factors affect oral microbiota composition and function; (2) the interaction between microenvironment and oral microbiota; (3) the role of multi-kingdom oral microbiota in human health; (4) the potential underlying mechanisms and therapeutic benefits of oral microbiota against cancer. Finally, we aim to describe the impact of oral microbiota on cancer progression and provide novel therapeutic insights into cancer prevention and treatment by targeting oral microbiota.

Phenomics期刊简介

Phenomics是一本新创的同行评审国际期刊，聚焦表型组学前沿研究，搭建全球表型组学领域专家交流的国际平台，推动该领域相关的理论创新和学科发展。

本期刊拥有强大的国际编委团队，复旦大学金力院士担任主编，美国系统生物学研究所Leroy Hood院士、澳大利亚莫道克大学Jeremy Nicholson院士、德国莱布尼兹环境医学研究所Jean Krutmann院士、复旦大学唐惠儒教授共同担任副主编，复旦大学丁琛教授担任执行主编，另有来自全球多国的三十多位著名科学家共同组成编委团队，以及四十多位青年科学家组成青年编委团队。

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