International Journal of Molecular Sciences

Journal Browser

► Journal Browser

Advances in Bioinformatics and Multi-Omics Applications in Cancer Research

Share This Special Issue

Special Issue Editor

Dr. Yang Shi

E-Mail Website
Guest Editor

Department of Oncology, School of Medicine, Karmanos Cancer Institute (KCI), Wayne State University (WSU), Detroit, MI, USA
Interests: bioinformatics and multi-omics data analysis in cancer research; statistical and machine learning approaches with applications in biomedical data analysis; computational statistics and monte carlo methods with applications in biomedical research

Special Issue Information

Dear Colleagues,

Recent advances in high-throughput technologies have enabled the generation of large-scale multi-omics datasets, including genomics, transcriptomics, epigenomics, proteomics, and metabolomics. The application and integration of these complex data using bioinformatics and computational approaches have become essential for uncovering the molecular mechanisms driving cancer initiation, progression, and therapeutic response.

This Special Issue aims to highlight recent developments and applications of bioinformatics and multi-omics data analysis in cancer research. We welcome original research and comprehensive reviews that address innovative computational methods, integrative analysis pipelines, machine learning and AI-driven approaches, as well as novel insights into cancer biology derived from multi-omics data. Topics of interest include, but are not limited to, biomarker discovery, patient stratification, therapeutic target identification, tumor heterogeneity, single-cell and spatial multi-omics, and systems biology approaches.

By bringing together interdisciplinary contributions, this Special Issue seeks to advance our understanding of cancer mechanisms and support the development of precision oncology strategies.

Dr. Yang Shi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.

Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.

Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.

External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.

Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (1 paper)

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

23 pages, 28542 KB

Open AccessArticle

A Comprehensive Analysis of Novel Variations Associated with Bile Duct Cancer: Insights into Expression, Methylation, and 3D Protein Structure

by Alper Bülbül, Gizel Gerdan, Cansu Portakal, Sudenaz Bajrami and Cemaliye Boylu Akyerli

Int. J. Mol. Sci. 2025, 26(23), 11244; https://doi.org/10.3390/ijms262311244 - 21 Nov 2025

Viewed by 512

Abstract

Cholangiocarcinoma is a rare but highly lethal cancer of the biliary epithelium, marked by heterogeneous molecular subtypes, unclear etiology, and poor five-year survival, highlighting the need for new diagnostic and therapeutic strategies; therefore, this study integrates genomic, transcriptomic, single-cell, methylomic, and molecular-dynamics data to pinpoint pathogenic variants. We performed an integrative multi-omics analysis of publicly available datasets. Somatic variants from 23 tumor samples in The Cancer Genome Atlas were annotated with 11 pathogenicity tools (AUC ≥ 0.86 across EVE, REVEL, SIFT, AlphaMissense, DEOGEN2 were the most stringent). Differential gene expression was assessed in matched bulk RNA-seq (tumor vs. non-tumor) using DESeq2 with Benjamini–Hochberg FDR correction. A single-cell RNA-seq dataset comprising 23,782 cells from an intrahepatic cholangiocarcinoma was clustered with marker genes identified by Wilcoxon rank-sum tests. Illumina 450 K methylation arrays (52 tumors, 12 normal livers) were analyzed with limma and DMRcate to detect differentially methylated probes and regions. AlphaFold3 models of wild-type and MAP2K1^R49C were subjected to 50 ns all-atom molecular-dynamics simulations in GROMACS; conformational shifts were quantified by RMSD/RMSF and stability tested with FoldX5. Twenty-four tumor-specific missense variants were detected. The four highest-confidence pathogenic substitutions (EVE, REVEL, SIFT, AlphaMissense, DEOGEN2) occurred in TUBB3, FLNC, ABCA1, and MAP2K1. Bulk RNA-seq confirmed significant dysregulation of these genes and enrichment of extracellular-matrix organization, cytoskeletal remodeling, MAPK signaling, and cholesterol-efflux pathways. Single-cell analysis resolved 23 transcriptionally distinct clusters; proliferative malignant cholangiocytes selectively over-expressed ABCA1 and MAP2K1, indicating tumor-cell specificity. Methylome profiling identified 148,928 DMPs and 7040 DMRs; promoter hypomethylation of TUBB3 and ABCA1 correlated with their transcriptional activation. Substituting Arg-49 with Cys in MAP2K1 dismantles the Arg-centred hydrogen-bond/salt-bridge cluster, reduces hydrophobic packing, and, corroborated by 50 ns MD (Welch’s t = −58.06, p = 3.17 × 10⁻²³⁰) and FoldX5 (

Δ Δ

G = +2.3 kcal mol⁻¹), significantly destabilises the protein, manifesting as higher backbone RMSD and increased local flexibility relative to wild type. This multi-omics, public data-driven synthesis delineates a coherent network of genomic, epigenomic, transcriptomic, and structural vulnerabilities, offering a rational framework for therapeutic targeting of cholangiocarcinoma. This study reveals novel bile duct-associated variations that expand our understanding of cholangiocarcinoma pathogenesis and provide potential targets for precision medicine approaches. Full article

(This article belongs to the Special Issue Advances in Bioinformatics and Multi-Omics Applications in Cancer Research)

► Show Figures

Journal Menu

Journal Browser

Advances in Bioinformatics and Multi-Omics Applications in Cancer Research

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (1 paper)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI