Methods and Applications: Computational Genomics

Editors

Guanglin Li

Shaanxi Normal University

Tao Huang

Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences (CAS)

Impact

Original Research

13 May 2022

Identification of Novel Imatinib-Resistant Genes in Gastrointestinal Stromal Tumors

Lei Cao

, 7 more and

Yongjie Zhao

3,228 views

4 citations

Original Research

26 April 2022

A Systematic Screening of ADHD-Susceptible Variants From 25 Chinese Parents–Offspring Trios

Qianqian Li

, 4 more and

Wei Sun

2,147 views

2 citations

Data provenance on the consortium blockchain. Data provenance could be carried out through referring to dataset files, hash values, operation description, operators, time, and other information stored on the blockchain.

Original Research

13 April 2022

PHDMF: A Flexible and Scalable Personal Health Data Management Framework Based on Blockchain Technology

Liangxiao Ma

, 6 more and

Yun Xiong

2,350 views

4 citations

Prediction of new COVID-19 cases with Sample Entropy values of the latent dimensions. (A) Line plot showing the Entropy values of the selected features and new COVID-19 cases for the United States (B) Actual and predicted cases based on the entropy values of selected features for the United States. The model predicts a rise in cases for July and August 2021. (C) Entropy of selected features and new cases for Japan. (D) Actual and predicted cases for Japan. A spike in cases is predicted for July and August 2021. (E) Entropy of selected features and new cases for India. (F) Actual and predicted cases for India.

Original Research

08 April 2022

Genomic Surveillance of COVID-19 Variants With Language Models and Machine Learning

Sargun Nagpal

, 9 more and

Tavpritesh Sethi

The global efforts to control COVID-19 are threatened by the rapid emergence of novel SARS-CoV-2 variants that may display undesirable characteristics such as immune escape, increased transmissibility or pathogenicity. Early prediction for emergence of new strains with these features is critical for pandemic preparedness. We present Strainflow, a supervised and causally predictive model using unsupervised latent space features of SARS-CoV-2 genome sequences. Strainflow was trained and validated on 0.9 million sequences for the period December, 2019 to June, 2021 and the frozen model was prospectively validated from July, 2021 to December, 2021. Strainflow captured the rise in cases 2 months ahead of the Delta and Omicron surges in most countries including the prediction of a surge in India as early as beginning of November, 2021. Entropy analysis of Strainflow unsupervised embeddings clearly reveals the explore-exploit cycles in genomic feature-space, thus adding interpretability to the deep learning based model. We also conducted codon-level analysis of our model for interpretability and biological validity of our unsupervised features. Strainflow application is openly available as an interactive web-application for prospective genomic surveillance of COVID-19 across the globe.

5,957 views

10 citations

Cell type diversity statistic to summarize PBMCs composition across age groups. (A). Proportions of 12 cell types discovered in scRNA-seq of PBMCs from different age groups. Each bar represents the proportions of lymphocyte (blue-green gradient) and myeloid (red-yellow gradient) cell types (y-axis) in a sample. (B). Each boxplot represents the distribution of the diversity statistic of the proportions of lymphocyte and myeloid cells in younger, middle, older, and extreme old age individuals (x-axis). The differences of the statistics across age groups were statistically significant (F-test p-value = 0.0001873) (C). Each boxplot represents the distribution of the diversity statistic of the proportions of the 12 cell types grouped by younger, middle, older, and extreme old age (x-axis). The differences of the statistics across age groups were statistically significant (F-test p-value = 0.0001875). The diversity statistic was significantly higher, in the extreme old age group compared to each younger age control group: younger age group (t-test p-value = 0.00115), middle age group (t-test p-value = 0.00016), and older age group (t-test p-value = 0.00363).

Methods

08 April 2022

Cell Type Diversity Statistic: An Entropy-Based Metric to Compare Overall Cell Type Composition Across Samples

Tanya T Karagiannis

, 1 more and

Paola Sebastiani

3,011 views

11 citations

Correlation of the risk score with clinicopathological variables, immune cells, PD-L1 expression, and TMB scores (A,B) A comparison of 5-year ROC curves (A) and correlation analysis (B) between risk scores and traditional clinicopathologic variables. (C) Spearman analysis between risk scores and ICI with seven common methods. (D) Different PD-L1 expression levels in the high-risk and low-risk groups. (E) Compared TMB level in the high-risk and low-risk groups. *p < 0.05; **p < 0.01; and ***p < 0.001.

Original Research

31 March 2022

Correlation Between Immune Cell Infiltration and PD-L1 Expression and Immune-Related lncRNA Determination in Triple-Negative Breast Cancer

Wenlin Yang

, 6 more and

Ting Wang

3,320 views

7 citations

The proposed mechanism for the MIO in HAL and GFP formation by posttranslational modification.

Systematic Review

29 March 2022

Origin and Evolution of Enzymes with MIO Prosthetic Group: Microbial Coevolution After the Mass Extinction Event

Fei Peng

, 2 more and

Jens Rudat

3,982 views

5 citations

The workflow of the protein sentence representation.

Original Research

28 March 2022

InfersentPPI: Prediction of Protein-Protein Interaction Using Protein Sentence Embedding With Gene Ontology Information

Meijing Li

, 1 more and

Keun Ho Ryu

2,519 views

2 citations

Original Research

28 March 2022

Transcription Factor KLF7 Promotes Osteoclast Differentiation by Suppressing HO-1

Changhong Chen

, 7 more and

Rongkui Zhou

KLF7 is an upstream regulator of HO-1. (A) Venn plot for screening DE-TFs in osteoporosis. (B) Correlation analysis between KLF7 and HO-1 expressions. (C) KLF7 expression in high/low BDM population. (D) Predicted KLF7 binding sites on HO-1 TSS. (E) ChIP and qPCR assays of the enrichment of KLF7 on the HO-1 promoter region. *p < 0.05, ***p < 0.001.

Background: Osteoporosis is a common orthopedic disease with high prevalence in patients older than 50 years. Osteoporosis is often detected only after the fracture and is hard to treat. Therefore, it is of great significance to explore the molecular mechanism of the occurrence of osteoporosis.

Methods: The expression of Heme oxygenase-1 (HO-1) in people with different bone mineral density (BMD) was analyzed based on public databases. GenHacncer and JASPAR databases were adopted to search and verify the upstream transcription factor of HO-1. qRT-PCR, western blot and tartrate-resistant acid phosphatase assays were performed to explore the impact of HO-1 and Kruppel-like factor 7 (KLF7) on osteoclast differentiation. Chromatin immunoprecipitation (ChIP) assay confirmed the binding relationship between KLF7 and HO-1. Finally, Hemin, the agonist of HO-1, was applied in rescue assays, thereby verifying the mechanism of KLF7 modulating osteoclast differentiation by HO-1.

Results: Bioinformatics analysis revealed that HO-1 was highly-expressed while KLF7 lowly-expressed in people with high BMD. Besides, a potential binding site of KLF7 was found on the promoter region of HO-1. ChIP assay further manifested the targeting relationship between HO-1 and KLF7. Western blot and TRAP staining unveiled that osteoclast differentiation was suppressed by HO-1, while facilitated by KLF7. Rescue experiments indicated that over-expressed HO-1 could reverse of the promoting effect of KLF7 on osteoclast differentiation.

Conclusion: The study confirmed that osteoclast differentiation was promoted by KLF7 constraining HO-1, thereby facilitating osteoporosis. The cognation of the pathogenesis of osteoporosis was further enriched. New treatment could be developed on this basis.

2,574 views

14 citations

Differential co-expressed gene networks in the blue (A) and darkred (B) modules from GSE134347. Each node represented one gene. Each edge represented correlation between two genes, in which red meant positive correlation and green negative correlation. The thicker edge represented the stronger correlation coefficient.

Original Research

24 March 2022

Identification of Hub Genes With Differential Correlations in Sepsis

Lulu Sheng

, 2 more and

Qiming Feng

3,318 views

7 citations

Original Research

23 March 2022

Cellular Interaction Analysis Characterizing Immunosuppressive Microenvironment Functions in MM Tumorigenesis From Precursor Stages

Zhenhao Liu

, 5 more and

Lu Xie

Cell–cell interaction event (CCEs) dysregulation may relate to the heterogeneity of the tumor microenvironment (TME) and would affect therapeutic responses and clinical outcomes. To reveal the alteration of the immune microenvironment in bone marrow from a healthy state to multiple myeloma (MM), scRNA-seq data of the four states, including healthy state normal bone marrow (NBM) and three disease states (MGUS, SMM, and MM), were collected for analysis. With immune microenvironment reconstruction, the cell types, including NK cells, CD8⁺ T cells, and CD4⁺ T cells, with a higher percentage in disease states were associated with prognosis of MM patients. Furthermore, CCEs were annotated and dysregulated CCEs were identified. The number of CCEs were significantly changed between disease states and NBM. The dysregulated CCEs participated in regulation of immune cell proliferation and immune response, such as MIF-TNFRSF14 interacted between early B cells and CD8⁺ T cells. Moreover, CCE genes related to drug response, including bortezomib and melphalan, provide candidate therapeutic markers for MM treatment. Furthermore, MM patients were separated into three risk groups based on the CCE prognostic signature. Immunoregulation-related differentiation and activation of CD4⁺ T cells corresponded to the progression status with moderate risk. These results provide a comprehensive understanding of the critical role of intercellular communication in the immune microenvironment over the evolution of premalignant MM, which is related to the tumorigenesis and progression of MM, which moreover, suggests a way of potential target selection for clinical intervention.

3,119 views

8 citations

Immune infiltration analysis in the three datasets. (A) The expression heatmap of 22 immune cells in GSE37069; (B) the expression heatmap of 22 immune cells in GSE8056; (C) the expression heatmap of 22 immune cells in GSE19743; (D) correlation heatmap of immune cells in burn injury.

Original Research

22 March 2022

Identification of Novel Biomarkers With Diagnostic Value and Immune Infiltration in Burn Injury

Sitong Zhou

, 6 more and

Ronghua Yang

3,509 views

2 citations

The degree distribution of lncRNAs in mouse network and human network with and without over-length lncRNAs. (A) The degree distribution of lncRNAs in mouse network with over-length lncRNAs; (B) The degree distribution of lncRNAs in mouse network without over-length lncRNAs; (C) The degree distribution of lncRNAs in human network with over-length lncRNAs; (D) The degree distribution of lncRNAs in human network without over-length lncRNAs.

Methods

21 March 2022

SGII: Systematic Identification of Essential lncRNAs in Mouse and Human Genome With lncRNA-Protein-Protein Heterogeneous Interaction Network

Xiao-Hong Xin

, 4 more and

Pu-Feng Du

2,016 views

4 citations

Visualization results of 17 mutants. The labels of first 11 mutants were confirmed in biological experiments, and the labels of last six mutants were speculated to be by their destroyed dimerization interface.

Original Research

15 March 2022

GLTM: A Global-Local Attention LSTM Model to Locate Dimer Motif of Single-Pass Membrane Proteins

Quanchao Ma

, 2 more and

Fan Yang

1,529 views

1 citations

Knockdown LINC00665 inhibited the proliferation of HCC cells, and overexpression of CIP2A-BP promoted proliferation of HCC cells. (A) Knockdown transfection of LINC00665 in HCC cells (si-LINC00665 #1 and si-LINC00665 #2). (B) The effect of si-LINC00665 #2 on the proliferation of MHCC97H cells. (C) The effect of si-LINC00665 #2 on the proliferation of SNU387 cells. (D) Overexpression transfection of CIP2A-BP in HCC cells. (E) The effect of over-CIP2A-BP on the proliferation of MHCC97H cells. (F) The effect of over-CIP2A-BP on the proliferation of SNU387 cells. *p < 0.05, **p < 0.01.

Original Research

08 March 2022

Mechanism Analysis of LINC00665 and Its Peptides CIP2A-BP in Hepatocellular Carcinoma

Yi-Ran Li

, 3 more and

Fei-Xiang Wu

2,136 views

15 citations

Reads correctly classified in the taxonomic analyses. True positives compared to the expected at species (A) and genus (C) levels. The proportion between these values at species (B) and genus levels (D).

Methods

07 March 2022

MEDUSA: A Pipeline for Sensitive Taxonomic Classification and Flexible Functional Annotation of Metagenomic Shotgun Sequences

Diego A. A. Morais

, 3 more and

Rodrigo J. S. Dalmolin

Metagenomic studies unravel details about the taxonomic composition and the functions performed by microbial communities. As a complete metagenomic analysis requires different tools for different purposes, the selection and setup of these tools remain challenging. Furthermore, the chosen toolset will affect the accuracy, the formatting, and the functional identifiers reported in the results, impacting the results interpretation and the biological answer obtained. Thus, we surveyed state-of-the-art tools available in the literature, created simulated datasets, and performed benchmarks to design a sensitive and flexible metagenomic analysis pipeline. Here we present MEDUSA, an efficient pipeline to conduct comprehensive metagenomic analyses. It performs preprocessing, assembly, alignment, taxonomic classification, and functional annotation on shotgun data, supporting user-built dictionaries to transfer annotations to any functional identifier. MEDUSA includes several tools, as fastp, Bowtie2, DIAMOND, Kaiju, MEGAHIT, and a novel tool implemented in Python to transfer annotations to BLAST/DIAMOND alignment results. These tools are installed via Conda, and the workflow is managed by Snakemake, easing the setup and execution. Compared with MEGAN 6 Community Edition, MEDUSA correctly identifies more species, especially the less abundant, and is more suited for functional analysis using Gene Ontology identifiers.

12,350 views

9 citations

Original Research

03 March 2022

Exosome-Derived LncRNA TCONS_00072128 Mediated Osteogenic Differentiation and Inflammation by Caspase 8 Regulation

Yongchang Yang

, 8 more and

Xiaoke Hao

Postmenopausal osteoporosis (PMOP) is a systemic metabolic bone disease in postmenopausal women. It has been known that long non-coding RNAs (lncRNAs) play a regulatory role in the progression of osteoporosis. However, the mechanism underlying the effects of exosome-derived lncRNA on regulating the occurrence and development of PMOP remains unclear. Exosomes in the serum of patients PMOP were collected and identified. RNA sequencing was performed to obtain the expression profile of exosome-derived lncRNAs in the serum of PMOP patients. RNA sequencing identified 26 differentially expressed lncRNAs from the exosomes between healthy people and PMOP patients. Among them, the expression of TCONS_00072128 was dramatically down-regulated. A co-location method was employed and searched its potential target gene caspase 8. TCONS_00072128 knockdown notably decreased the expression of caspase 8, while the osteogenic differentiation of BMSCs was also reduced. Reversely, TCONS_00072128 overexpression enhanced caspase 8 expression and osteogenic differentiation of BMSCs. Moreover, the continuous expression of caspase 8 regulated by TCONS_00072128 significantly activated inflammation pathways including NLRP3 signaling and NF-κB signaling. Simultaneously, RIPK1 which has emerged as a promising therapeutic target for the treatment of a wide range of human neurodegenerative, autoimmune, and inflammatory diseases, was also phosphorylated. The results of the present study suggested that exosome-derived lncRNA TCONS_00072128 could promote the progression of PMOP by regulating caspase 8. In addition, caspase 8 expression in BMSCs was possible to be a key regulator that balanced cell differentiation and inflammation activation.

3,962 views

17 citations