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Bioinformatics has revolutionized biology and medicine by using computational methods to analyze and interpret biological data. Quantum mechanics has recently emerged as a promising tool for the analysis of biological systems, leading to the development of quantum bioinformatics. This new field employs the principles of quantum mechanics, quantum algorithms, and quantum computing to solve complex problems in molecular biology, drug design, and protein folding. However, the intersection of bioinformatics, biology, and quantum mechanics presents unique challenges. One significant challenge is the possibility of confusion among scientists between quantum bioinformatics and quantum biology, which have similar goals and concepts. Additionally, the diverse calculations in each field make it difficult to establish boundaries and identify purely quantum effects from other factors that may affect biological processes. This review provides an overview of the concepts of quantum biology and quantum mechanics and their intersection in quantum bioinformatics. We examine the challenges and unique features of this field and propose a classification of quantum bioinformatics to promote interdisciplinary collaboration and accelerate progress. By unlocking the full potential of quantum bioinformatics, this review aims to contribute to our understanding of quantum mechanics in biological systems.
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Metodologias Computacionais , Teoria Quântica , Algoritmos , Biologia Computacional , Desenho de FármacosRESUMO
Omics data integration plays an essential role in manifesting hidden cancer insights. To detect the main combinatorial/parallel impact of cancer events, integrative approaches in pan-cancer studies must be used. Here, we assessed gastrointestinal (GI) cancers from several perspectives of genomics, transcriptomics, epigenomics, and also combinatorial impacts using a novel integrative approach to score genes. Next, scores were diffused on a signaling network and extracted subnetworks. We also implemented our new scoring method to compare upper-/lower-GI cancers, investigate the regulatory mechanisms of lncRNAs, and detect amplifications/deletions between GI and non-GI cancers. The integrative subnetwork indicated the interplay among essential protein families in the cell cycle. The copy-number-variation-related subnetwork revealed minor cell cycle and immune effects, whereas the methylation-related subnetwork revealed significant immune effects. The top-score lncRNAs indicated a distinct regulatory pattern for lower-/upper-, and accessory-GI categories. In summary, cell cycle dysfunction might be largely the consequence of combinatorial abnormalities.
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Neoplasias Gastrointestinais , Projetos de Pesquisa , Ciclo Celular/genética , Variações do Número de Cópias de DNA , Epigenômica , Neoplasias Gastrointestinais/genética , HumanosRESUMO
Brain metastasis in basal-like breast cancer poses a significant challenge in cancer management due to its aggressive nature and limited treatment options. This study conducted a comprehensive analysis to explore the potential role of circular RNAs (circRNAs) as members of endogenous networks in developing breast cancer brain metastasis. Here, we utilized RNA sequencing data from primary breast cancer and brain metastasis tissue with basal-like subtype (n = 11). After quality controlling and preprocessing of fastq files, gene expression of mRNA and circRNAs were extracted from matched samples and normalized. Then, we employed the weighted gene co-expression network analysis approach to identify brain metastasis-associated circRNA modules ( S p e a r m a n Correlation > 0.5 , P - value < 0.05 ). Moreover, we found five protein-coding genes of PHLDA1, SLC12A2, MMP2, RGP1, and MAP2K6, significantly upregulated in brain metastatic tissues compared to primary breast cancer ( FDR < 0.05 ). These genes were enriched in the "GnRH signaling pathway" and "Fluid shear stress and atherosclerosis" pathways ( FDR < 0.05 ). Next, to explore the potential interactions between circRNAs and protein-coding genes, we reconstructed a competing endogenous RNA (ceRNA) network using mutual miRNAs between the circRNA module and upregulated mRNAs. Notably, we could detect two axes of circ_0087558/miR-604/MMP2 and MMP2/miR-1248/Circ_0087558/miR-643/MAP2K6 in ceRNA network. In conclusion, the identified circRNA-miRNA-mRNA axes might be therapeutic targets or diagnostic biomarkers for this challenging subtype of breast cancer. However, due to the small number of samples, further experimental validations are essential.
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BACKGROUND: In recent years, drug screening has been one of the most significant challenges in the field of personalized medicine, particularly in cancer treatment. However, several new platforms have been introduced to address this issue, providing reliable solutions for personalized drug validation and safety testing. In this study, we developed a personalized drug combination protocol as the primary input to such platforms. METHODS: To achieve this, we utilized data from whole-genome expression profiles of 6173 breast cancer patients, 312 healthy individuals, and 691 drugs. Our approach involved developing an individual pattern of perturbed gene expression (IPPGE) for each patient, which was used as the basis for drug selection. An algorithm was designed to extract personalized drug combinations by comparing the IPPGE and drug signatures. Additionally, we employed the concept of drug repurposing, searching for new benefits of existing drugs that may regulate the desired genes. RESULTS: Our study revealed that drug combinations obtained from both specialized and non-specialized cancer medicines were more effective than those extracted from only specialized medicines. Furthermore, we observed that the individual pattern of perturbed gene expression (IPPGE) was unique to each patient, akin to a fingerprint. CONCLUSIONS: The personalized drug combination protocol developed in this study offers a methodological interface between drug repurposing and combination drug therapy in cancer treatment. This protocol enables personalized drug combinations to be extracted from hundreds of drugs and thousands of drug combinations, potentially offering more effective treatment options for cancer patients.
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Neoplasias , Medicina de Precisão , Humanos , Medicina de Precisão/métodos , Biologia Computacional , Quimioterapia Combinada , Neoplasias/tratamento farmacológico , Neoplasias/genética , Combinação de MedicamentosRESUMO
Background: The WASF3 gene has been linked to promoting metastasis in breast cancer (BC) cells, and low expression reduces invasion potential. Circular RNAs (circRNAs) function as microRNA (miRNA) modulators and are involved in cancer progression, but the relationship between these factors remains unclear. Methods: This study used bioinformatics methods and a computational approach to investigate the role of circRNAs and miRNAs in the context of WASF3 overexpression. Differentially expressed mRNAs, circRNAs, and miRNAs were identified using Gene Expression Omnibus (GEO) datasets. A competing endogenous RNA (ceRNA) network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Functional and pathway enrichment analyses were predicted using a circRNA-miRNA-mRNA network. Results: RNA expression patterns were significantly different between normal and tumor samples. A total of 190 circRNAs, 76 miRNAs, and 678 mRNAs were differentially expressed. The analysis of the circRNA-miRNA-mRNA regulatory network revealed interactions between hsa-circ-0100153, hsa-miR-31, hsa-miR-767-3p, and hsa-miR-935 with WASF3 in cancer. These interactions primarily function in DNA replication and the cell cycle. Conclusions: This study reveals a mechanism by which WASF3 overexpression affects the expression of circRNAs hsa-circ-0100153, promoting BC progression by sponging hsa-miR-31/hsa-miR-767-3p /hsa-miR-935. This mechanism may increase the invasive potential of cancers, in addition to other reported molecular mechanisms involving the WASF3 gene.
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BACKGROUND: Elucidating the dynamic topological changes across different stages of breast cancer, called stage re-wiring, could lead to identifying key latent regulatory signatures involved in cancer progression. Such dynamic regulators and their functions are mostly unknown. Here, we reconstructed differential co-expression networks for four stages of breast cancer to assess the dynamic patterns of cancer progression. A new computational approach was applied to identify stage-specific subnetworks for each stage. Next, prognostic traits of genes and the efficiency of stage-related groups were evaluated and validated, using the Log-Rank test, SVM classifier, and sample clustering. Furthermore, by conducting the stepwise VIF-feature selection method, a Cox-PH model was developed to predict patients' risk. Finally, the re-wiring network for prognostic signatures was reconstructed and assessed across stages to detect gain/loss, positive/negative interactions as well as rewired-hub nodes contributing to dynamic cancer progression. RESULTS: After having implemented our new approach, we could identify four stage-specific core biological pathways. We could also detect an essential non-coding RNA, AC025034.1, which is not the only antisense to ATP2B1 (cell proliferation regulator), but also revealed a statistically significant stage-descending pattern; Moreover, AC025034.1 revealed both a dynamic topological pattern across stages and prognostic trait. We also identified a high-performance Overall-Survival-Risk model, including 12 re-wired genes to predict patients' risk (c-index = 0.89). Finally, breast cancer-specific prognostic biomarkers of LINC01612, AC092142.1, and AC008969.1 were identified. CONCLUSIONS: In summary new scoring method highlighted stage-specific core pathways for early-to-late progressions. Moreover, detecting the significant re-wired hub nodes indicated stage-associated traits, which reflects the importance of such regulators from different perspectives.
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Neoplasias da Mama , RNA não Traduzido/genética , Neoplasias da Mama/genética , Feminino , Expressão Gênica , Humanos , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , PrognósticoRESUMO
BACKGROUND: Aberrant levels of 5-hydroxymethylcytosine (5-hmC) can lead to cancer progression. Identification of 5-hmC-related biological pathways in cancer studies can produce better understanding of gastrointestinal (GI) cancers. We conducted a network-based analysis on 5-hmC levels extracted from circulating free DNAs (cfDNA) in GI cancers including colon, gastric, and pancreatic cancers, and from healthy donors. The co-5-hmC network was reconstructed using the weighted-gene co-expression network method. The cancer-related modules/subnetworks were detected. Preservation of three detected 5-hmC-related modules was assessed in an external dataset. The 5-hmC-related modules were functionally enriched, and biological pathways were identified. The relationship between modules was assessed using the Pearson correlation coefficient (p-value < 0.05). An elastic network classifier was used to assess the potential of the 5-hmC modules in distinguishing cancer patients from healthy individuals. To assess the efficiency of the model, the Area Under the Curve (AUC) was computed using five-fold cross-validation in an external dataset. RESULTS: The main biological pathways were the cell cycle, apoptosis, and extracellular matrix (ECM) organization. Direct association between the cell cycle and apoptosis, inverse association between apoptosis and ECM organization, and inverse association between the cell cycle and ECM organization were detected for the 5-hmC modules in GI cancers. An AUC of 92% (0.73-1.00) was observed for the predictive model including 11 genes. CONCLUSION: The intricate association between biological pathways of identified modules may reveal the hidden significance of 5-hmC in GI cancers. The identified predictive model and new biomarkers may be beneficial in cancer detection and precision medicine using liquid biopsy in the early stages.
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Ácidos Nucleicos Livres , Neoplasias Gastrointestinais , Apoptose/genética , Ciclo Celular/genética , Ácidos Nucleicos Livres/genética , Matriz Extracelular/genética , Neoplasias Gastrointestinais/genética , HumanosRESUMO
BACKGROUND: Circulating tumor cells (CTCs) are the critical initiators of distant metastasis formation. In which, the reciprocal interplay among different metastatic pathways and their metastasis driver genes which promote survival of CTCs is not well introduced using network approaches. METHODS: Here, to investigate the unknown pathways of single/cluster CTCs, the co-expression network was reconstructed, using WGCNA (Weighted Correlation Network Analysis) method. Having used the hierarchical clustering, we detected the Immune-response and EMT subnetworks. The metastatic potential of genes was assessed and validated through the support vector machine (SVM), neural network, and decision tree methods on two external datasets. To identify the active signaling pathways in CTCs, we reconstructed a casual network. The Log-Rank test and Kaplan-Meier curve were applied to detect prognostic gene signatures for distant metastasis-free survival (DMFS). Finally, a predictive model was developed for metastasis risk of patients using VIF-stepwise feature selection. RESULTS: Our results showed the crosstalk among EMT, the immune system, menstrual cycles, and the stemness pathway in CTCs. In which, fluctuation of menstrual cycles is a new detected pathway in breast cancer CTCs. The reciprocal association between immune responses and EMT was identified in CTCs. The SVM model indicated a high metastatic potential of EMT subnetwork (accuracy, sensitivity, and specificity scores were 87%). The DMFS model was identified to predict patients' metastasis risks. (c-index = 0.7). Finally, novel metastatic biomarkers of KRT18 and KRT19 were detected in breast cancer CTCs. CONCLUSIONS: In conclusion, the reciprocal interplay among critical unknown pathways in CTCs manifests both their survival in blood and metastatic potentials. Such findings may help to develop more precise predictive metastatic-risk models or detect pivotal metastatic biomarkers.