Author Archives: gene_x

微生物与病毒生物信息学 vs. 细菌与病毒生物信息学

核心区别

  • Microbial & Viral Bioinformatics(微生物与病毒生物信息学)
    研究对象更广,涵盖所有类型的微生物(细菌、古菌、真菌、原生生物等)以及病毒。
  • Bacterial and Viral Bioinformatics(细菌与病毒生物信息学)
    研究对象较窄,专注于细菌和病毒,不包括其他非细菌类微生物。
Bacterial_and_Viral_Bioinformatics

对比表

维度 微生物与病毒生物信息学 细菌与病毒生物信息学
研究对象范围 微生物(细菌、古菌、真菌、原生生物等)+ 病毒 仅限细菌 + 病毒
广度 广,涵盖多类生物 窄,专注于细菌相关
典型研究方向 宏基因组学、群落生态学、宿主-微生物互作、病毒-微生物关系 细菌基因组学、耐药基因预测、病原体分析、噬菌体研究
应用场景 微生物群落研究、环境样本分析、人体微生物组研究 医学细菌学、传染病、抗生素耐药机制
学科定位 偏向综合性、生态学与系统层面 偏向临床、病原学与应用层面

应用实例对比

  • 微生物与病毒生物信息学

    • 实例:分析人类肠道微生物组(细菌、真菌、古菌等)与病毒群落的互作,探索其与肥胖、糖尿病或免疫系统疾病的关系。
    • 特点:关注整体微生物生态系统,强调多类生物之间的协同与平衡。
  • 细菌与病毒生物信息学

    • 实例:研究医院获得性耐药细菌(如耐甲氧西林金黄色葡萄球菌,MRSA)及其与噬菌体的互作,寻找新的治疗策略。
    • 特点:聚焦病原体与临床应用,强调对疾病防控和治疗的直接价值。

总结

  • Microbial & Viral Bioinformatics:范围大,适合研究多样微生物群落及其与病毒的关系。
  • Bacterial and Viral Bioinformatics:范围小,专注于细菌和病毒,更聚焦临床和病原学研究。

import matplotlib.pyplot as plt
from matplotlib_venn import venn2

# Create side-by-side comparison
fig, axes = plt.subplots(1, 2, figsize=(12,6))

# --- Left: Microbial & Viral ---
venn_left = venn2(
    subsets=(1, 1, 1),
    set_labels=("Microbes", "Viruses"),
    ax=axes[0],
    set_colors=("skyblue", "lightcoral"),  # 微生物用蓝色,病毒用红色
    alpha=0.6
)
venn_left.get_label_by_id('10').set_text('Bacteria, Archaea,\nFungi, Protists')
venn_left.get_label_by_id('01').set_text('Viruses')
venn_left.get_label_by_id('11').set_text('Microbe-Virus\ninteractions')
axes[0].set_title("Microbial & Viral Bioinformatics")

# --- Right: Bacterial & Viral ---
venn_right = venn2(
    subsets=(1, 1, 1),
    set_labels=("Bacteria", "Viruses"),
    ax=axes[1],
    set_colors=("lightgreen", "lightcoral"),  # 细菌用绿色,病毒用红色
    alpha=0.6
)
venn_right.get_label_by_id('10').set_text('Bacteria\n(pathogens, commensals)')
venn_right.get_label_by_id('01').set_text('Viruses\n(phages, human viruses)')
venn_right.get_label_by_id('11').set_text('Bacteria-Virus\ninteractions')
axes[1].set_title("Bacterial & Viral Bioinformatics")

# Add a caption below the plots
fig.text(
    0.5, -0.05,
    "Comparison: Microbial & Viral Bioinformatics covers all microbes (bacteria, archaea, fungi, protists) plus viruses,\n"
    "while Bacterial & Viral Bioinformatics is narrower, focusing only on bacteria and viruses.",
    ha='center', fontsize=10
)

plt.tight_layout()
plt.show()
import matplotlib.pyplot as plt

fig, ax = plt.subplots(figsize=(6,6))

# 大圆 - Microbial
microbe_circle = plt.Circle((0,0), 1.0, color="skyblue", alpha=0.4, label="Microbes")
ax.add_artist(microbe_circle)

# 小圆 - Bacteria (在Microbial里)
bacteria_circle = plt.Circle((0.3,0.3), 0.4, color="lightgreen", alpha=0.6, label="Bacteria")
ax.add_artist(bacteria_circle)

# 另一个圆 - Viruses
virus_circle = plt.Circle((-0.2,-0.2), 0.6, color="lightcoral", alpha=0.6, label="Viruses")
ax.add_artist(virus_circle)

# 设置比例 & 美化
ax.set_xlim(-1.5, 1.5)
ax.set_ylim(-1.5, 1.5)
ax.set_aspect("equal")
ax.axis("off")

# 添加标签
ax.text(-0.9, 1.0, "Microbes\n(bacteria, archaea, fungi, protists)", fontsize=10, color="blue")
ax.text(0.4, 0.6, "Bacteria", fontsize=10, color="green")
ax.text(-0.9, -0.8, "Viruses", fontsize=10, color="red")

plt.title("Nested Scope: Microbes vs Bacteria with Viruses", fontsize=12)
plt.show()

Analyse spatial transcriptomic data

Click here (http://xgenes.com/course/spatialtx/) to get started.

Analyzing spatial transcriptomic data involves several steps, including quality control, data pre-processing, spatial mapping, cell-type identification, differential expression analysis, and functional analysis. Here are the main steps involved in spatial transcriptomic data analysis:

Quality control: This step involves checking the quality of the sequencing reads using tools such as FastQC. If the quality is low, the data may need to be re-sequenced or filtered to remove low-quality reads or adapter sequences. Data pre-processing: This step involves filtering out low-quality cells, normalizing the data, and identifying highly variable genes using tools such as ST Pipeline or STARmap. Spatial mapping: This step involves mapping the transcriptomic data to the spatial coordinates of the tissue sections using tools such as ST Pipeline or STARmap. This produces a spatial expression matrix that contains the expression levels of each gene in each spatial location. Cell-type identification: This step involves identifying the cell types that are present in each spatial location using tools such as CellFinder or SpatialDE. Differential expression analysis: This step involves identifying genes that are differentially expressed between different spatial locations or cell types. This can be done using tools such as ST Pipeline or SpatialDE. Functional analysis: This step involves interpreting the differentially expressed genes by performing pathway or gene ontology analysis. This can be done using tools such as GSEA or Enrichr. Data visualization: This step involves visualizing the results of the analysis using tools such as heatmaps, spatial plots, or 3D visualizations. Overall, analyzing spatial transcriptomic data is a complex process that involves several steps and tools. It is important to carefully QC the data, choose appropriate normalization and statistical methods, and interpret the results in the context of the biological question being studied. Additionally, there are specialized tools and methods available for different types of spatial transcriptomic data, such as MERFISH or CODEX, which may require different analysis pipelines.

Anlalyse single cell transcriptomic data

Click here (http://xgenes.com/course/singlecelltx/) to get started.

Analyzing single-cell transcriptomic data involves several steps, including quality control, data pre-processing, cell clustering, differential expression analysis, and functional analysis. Here are the main steps involved in single-cell transcriptomic data analysis:

Quality control: This step involves checking the quality of the sequencing reads using tools such as FastQC. If the quality is low, the data may need to be re-sequenced or filtered to remove low-quality reads or adapter sequences. Data pre-processing: This step involves filtering out low-quality cells, normalizing the data, and identifying highly variable genes using tools such as Seurat or Scanpy. Cell clustering: This step involves grouping cells that have similar gene expression profiles into clusters using unsupervised clustering algorithms such as k-means or hierarchical clustering. This can be done using tools such as Seurat, Scanpy, or RaceID. Differential expression analysis: This step involves identifying genes that are differentially expressed between different clusters of cells. This can be done using tools such as Seurat or Scanpy. Functional analysis: This step involves interpreting the differentially expressed genes by performing pathway or gene ontology analysis. This can be done using tools such as GSEA or Enrichr. Data visualization: This step involves visualizing the results of the analysis using tools such as t-SNE, UMAP, or heatmaps. Overall, analyzing single-cell transcriptomic data is a complex process that involves several steps and tools. It is important to carefully QC the data, choose appropriate normalization and statistical methods, and interpret the results in the context of the biological question being studied. Additionally, there are specialized tools and methods available for different types of single-cell transcriptomic data, such as scRNA-seq, scATAC-seq, or spatial transcriptomics, which may require different analysis pipelines.

Anlalyse RNA-seq data

Click here (http://xgenes.com/course/rnaseq/) to get started.

Analyzing RNA-seq data involves several steps, including quality control, alignment or mapping of the reads to a reference genome or transcriptome, quantification of gene expression, normalization, differential gene expression analysis, and functional analysis of the differentially expressed genes. Here are the main steps involved in RNA-seq data analysis:

Quality control: This step involves checking the quality of the sequencing reads using tools such as FastQC. If the quality is low, the data may need to be re-sequenced or trimmed to remove low-quality reads or adapter sequences. Alignment or mapping: This step involves aligning the sequencing reads to a reference genome or transcriptome using tools such as HISAT2, STAR, or Tophat. This step produces alignment files (in BAM or SAM format) that are used in the next step. Quantification: This step involves quantifying gene expression levels from the aligned reads using tools such as featureCounts or HTSeq. This produces a count matrix that contains the number of reads mapped to each gene. Normalization: This step involves normalizing the count matrix to account for differences in sequencing depth or library size between samples. Common normalization methods include TMM or FPKM. Differential gene expression analysis: This step involves identifying genes that are differentially expressed between two or more groups of samples. This is typically done using statistical tests such as the Wald test or the Likelihood Ratio test in packages such as DESeq2, edgeR, or limma-voom. Functional analysis: This step involves interpreting the differentially expressed genes by performing pathway or gene ontology analysis. This can be done using tools such as DAVID, Enrichr, or GSEA. Overall, analyzing RNA-seq data is a complex process that involves several steps and tools. It is important to carefully QC the data, choose appropriate normalization and statistical methods, and interpret the results in the context of the biological question being studied.

Explore microbiome data with Phyloseq

Click here (http://xgenes.com/course/phyloseq/) and Click here (http://xgenes.com/course/phyloseq2/) to get started.

Phyloseq is an R package for the analysis of microbiome data. Microbiome data is generated from high-throughput sequencing technologies such as 16S rRNA gene sequencing or metagenomic sequencing, which allow for the identification and quantification of the microbial species present in a given sample.

Phyloseq provides a framework for importing, analyzing, and visualizing microbiome data in R. It allows users to perform a wide range of analyses, including alpha and beta diversity analyses, differential abundance testing, and network analysis. Additionally, Phyloseq integrates with other R packages for statistical analysis and data visualization.

Overall, Phyloseq provides a powerful toolset for exploring microbiome data and generating insights into the microbial communities present in a given sample.

Align Sequences with MUSCLE

Click here (http://sishi.com/muscleform) to get started.

MUSCLE (Multiple Sequence Comparison by Log-Expectation) is a software program used for multiple sequence alignment of nucleotide or protein sequences. It is a fast and efficient program that can align large numbers of sequences with high accuracy. It was developed by Robert C. Edgar, who first described it in a paper titled “MUSCLE: multiple sequence alignment with high accuracy and high throughput” published in the journal Nucleic Acids Research in 2004.

Optimize your RNA secondary structure with RNAHeliCes

Click here (http://sishi.com/rnahelicesform) to get started.

RNAHeliCes is a computational tool used to analyze RNA folding space. RNA molecules can fold into a variety of structures, and understanding the folding process is important for studying their biological functions. RNAHeliCes uses a simplified representation of RNA structures, in which each structure is abstracted using position-specific helices. This approach allows RNAHeliCes to analyze large RNA datasets efficiently, by reducing the complexity of the structures and focusing on their most important features.

The method behind RNAHeliCes was developed by a team of researchers led by Jiabin Huang, Rolf Backofen, and Björn Voß. The work was published in the scientific journal RNA in 2012, and the paper is titled “Abstract folding space analysis based on helices.” The paper describes the method in detail, including how the helix-based abstraction is implemented and how it can be used to analyze RNA folding space. We also provide examples of how RNAHeliCes can be used to analyze RNA molecules with known structures, and how it can be used to predict the structures of RNA molecules with unknown structures.

DNA测序数据分析

dna_seq_banner
dna_seq_data_analysis

通过DNA测序数据分析了解遗传变异和突变的影响。

DNA测序有多种形式,包括全基因组测序(WGS)、全外显子组测序(WES)和目标测序,可以研究遗传和体细胞DNA变异。除了NGS数据外,SNP和CGH阵列也可用于识别遗传多态性和拷贝数变异。微生物群落的宏基因组全基因组测序可用于分析它们的组成和功能。

我们经常分析DNA序列数据来回答基础生物学和生物医学设置中的研究问题。以下是一些典型的DNA测序数据分析。

变异分析

在大多数情况下,DNA测序用于识别和分析遗传变异。这些变异可以是小的核苷酸置换、插入、删除、拷贝数改变或结构变异。此外,它们可能是遗传多态性或体细胞突变。

变异分析通常从原始DNA测序数据的质量控制开始,并将测序读取与参考基因组进行比对。然后可以计算出样品与公共参考或不同样品之间不同的变异。

变异分析的关键部分是注释检测到的变异。注释,例如等位基因频率(在样本和gnomAD等公共数据库中),对蛋白质结构或基因调控的预测影响以及预测的致病性,可用于下游分析和解释中灵活选择或排名变异。

癌症研究中的变异分析通常侧重于识别加速肿瘤发生的体细胞突变(驱动突变)或可用于诊断患者或预测其疾病进程的突变。然而,非驱动突变(乘客)也携带信息。它们增加了对突变特征和癌细胞克隆性分析的可靠性。了解更多有关 癌症研究中的突变分析。

somatic_mutation_analysis.530x0-is

基因组组装

对于没有参考基因组或基因组高度动态的生物,DNA测序数据分析从组装一个全新的基因组开始。基因组组装受益于深度全基因组测序。

一个组装好的基因组会基于序列同源性、预测基因序列以及(如果有的话)来自同一生物体的RNA测序数据进行注释。如果存在近缘物种的注释基因组,可以通过将基因信息转移到新组装的基因组中来改进注释。

组装好的基因组的质量通过指标(如N50、L50以及高度保守的同源基因的完整性)进行评估。新的高质量基因组可以进行全基因组分析、群体遗传学等等!

genome_assembly

宏基因组学

宏基因组学提供了对生态位中微生物多样性的无偏视图,包括来自寄主生物体和土壤的样品。使用shot-gun全基因组测序数据,reads被组装成contigs并分配给物种或操作分类单元(OTUs)。

已确定的物种或OTUs被组织成系统发育并进行定量。通过使用公共数据库,可以确定序列社群中单个基因或多基因途径所带来的功能。

请注意,16S引物子测序是宏基因组测序的一种经济实惠的替代方法,可用于识别物种并构建系统发育,但不允许进行高质量的功能分析。

metagenomics

群体遗传学

从相关种群中采样的个体的全基因组测量包含有关群体结构、谱系和历史的丰富信息。非模式生物的群体遗传分析通常从基因组组装和注释开始,然后进一步确定样本群体中的遗传多态性。基于这些多态性及其等位基因频率的下游分析有助于研究物种形成和适应等进化现象。

典型的分析包括主成分分析、对群体内和群体间的遗传变异进行分析以识别受进化选择影响的位点,以及对群体混合、系统发育和人口历史的分析。

population_genetics3

全基因组关联分析

生物医学上的群体规模遗传分析旨在确定与相关表型或疾病相关的基因和变异。除了一些单基因遗传性很强的疾病外,大多数疾病需要大的群体级别样本量才能获得足够的统计力量以发现关联。这样的全基因组关联研究(GWAS)基于来自生物库或其他大型存储库的SNP阵列或DNA测序数据。

GWAS的结果会给出每个个体变异与研究疾病之间的关联的统计数据。对于多基因疾病,即使疾病具有很强的遗传性,单个变异也可能具有非常弱的效应大小。在这种情况下,可以使用多基因风险评分(PRS)来总结大量变异的效应,得出一个综合风险评分,具有潜在的临床应用。

gwas_and_prs2

The top 10 genes

  • TP53: The TP53 gene, also known as p53, is a tumor suppressor gene that plays a critical role in preventing cancer. Mutations in TP53 are present in up to 50% of all cancers and are associated with a worse prognosis. TP53 acts as a transcription factor, regulating the expression of genes involved in cell cycle control, DNA repair, and apoptosis. When DNA is damaged, p53 is activated, leading to cell cycle arrest, DNA repair, or apoptosis if the damage is too severe.

  • TNF: Tumor necrosis factor (TNF) is a cytokine that plays a critical role in the immune response to cancer and infectious diseases. TNF is produced by immune cells, such as macrophages and T cells, and can induce apoptosis in cancer cells. In addition, TNF has been targeted by drugs to treat autoimmune diseases, such as rheumatoid arthritis and psoriasis.

  • EGFR: Epidermal growth factor receptor (EGFR) is a transmembrane receptor that binds to epidermal growth factor (EGF) and other ligands to activate downstream signaling pathways. EGFR is frequently mutated in cancers, particularly in lung cancer, and mutations in EGFR can lead to resistance to chemotherapy and targeted therapies. EGFR-targeting drugs, such as gefitinib and erlotinib, have been developed to treat lung cancer and other cancers that overexpress EGFR.

  • VEGFA: Vascular endothelial growth factor A (VEGFA) is a protein that promotes angiogenesis, the formation of new blood vessels. VEGFA is overexpressed in many cancers, including breast, lung, and colon cancer, and plays a critical role in tumor growth and metastasis. Drugs targeting VEGFA, such as bevacizumab and ranibizumab, have been developed to inhibit angiogenesis and treat cancer.

  • APOE: Apolipoprotein E (APOE) is a protein involved in lipid metabolism and is important for the transportation of cholesterol and other lipids in the bloodstream. APOE has also been implicated in Alzheimer’s disease, as individuals with a certain APOE allele have an increased risk of developing the disease.

  • IL6: Interleukin 6 (IL6) is a cytokine that plays a critical role in the immune response to infection and inflammation. IL6 is produced by immune cells, such as T cells and macrophages, and can activate downstream signaling pathways that lead to inflammation and fever. IL6 has also been implicated in cancer, as high levels of IL6 in the bloodstream have been associated with a worse prognosis.

  • TGFB1: Transforming growth factor beta 1 (TGFB1) is a cytokine that plays a critical role in cell proliferation, differentiation, and immune regulation. TGFB1 is produced by immune cells, such as T cells and macrophages, and can activate downstream signaling pathways that lead to cell cycle arrest and apoptosis. In addition, TGFB1 has been implicated in cancer, as it can promote tumor growth and metastasis.

  • MTHFR (Methylenetetrahydrofolate reductase) is an enzyme that plays a critical role in the metabolism of amino acids. Specifically, MTHFR is involved in the conversion of homocysteine to methionine, which is essential for the production of S-adenosylmethionine (SAMe). SAMe is a methyl donor that is important for the methylation of DNA, RNA, and proteins, and is involved in many cellular processes including gene expression, protein synthesis, and cell signaling. Mutations in the MTHFR gene can lead to reduced activity of the enzyme, which can result in elevated levels of homocysteine in the blood. Elevated homocysteine levels have been linked to a number of health problems, including cardiovascular disease, stroke, and neural tube defects in newborns. Some studies have also suggested that MTHFR mutations may be associated with an increased risk of certain types of cancer, although the evidence is not conclusive.

  • ESR1 (Oestrogen receptor 1) is a protein that plays a critical role in the response to estrogen in many tissues, including the breast, uterus, and bone. The ESR1 gene codes for the estrogen receptor alpha, which is a nuclear receptor that binds to estrogen and regulates the expression of many genes. In breast cancer, ESR1 is often overexpressed, and is a major driver of the disease. Targeting ESR1 with drugs like tamoxifen or aromatase inhibitors has been a key strategy in the treatment of estrogen receptor-positive breast cancer.

  • AKT1 (also known as protein kinase B) is a serine/threonine kinase that is involved in many cellular processes, including cell proliferation, apoptosis, and metabolism. AKT1 is activated by a variety of stimuli, including growth factors, cytokines, and extracellular matrix proteins. Once activated, AKT1 phosphorylates a number of downstream targets, including transcription factors, enzymes, and cytoskeletal proteins, leading to changes in gene expression, metabolism, and cell morphology. Mutations in AKT1 have been identified in a number of different cancers, including breast, colorectal, and ovarian cancer. In many cases, these mutations lead to increased AKT1 activity, which can promote cell survival and proliferation, and can also confer resistance to chemotherapy and other cancer treatments. As a result, AKT1 inhibitors are being developed as a potential therapeutic strategy for cancer treatment.