Network-based drug repurposing for HPV-associated cervical cancer

Recent studies have increasingly revealed the connection between metabolic reprogramming and tumor progression. However, the specific impact of metabolic reprogramming on inter-patient heterogeneity and prognosis in lung adenocarcinoma (LUAD) still requires further exploration. Here, we introduced a cellular hierarchy framework according to a malignant and metabolic gene set, named malignant & metabolism reprogramming (MMR), to reanalyze 178,739 single-cell reference profiles. Furthermore, we proposed a three-stage ensemble learning pipeline, aided by genetic algorithm (GA), for survival prediction across 9 LUAD cohorts (n = 2066). Throughout the pipeline of developing the three stage-MMR (3 S-MMR) score, double training sets were implemented to avoid over-fitting; the gene-pairing method was utilized to remove batch effect; GA was harnessed to pinpoint the optimal basic learner combination. The novel 3 S-MMR score reflects various aspects of LUAD biology, provides new insights into precision medicine for patients, and may serve as a generalizable predictor of prognosis and immunotherapy response. To facilitate the clinical adoption of the 3 S-MMR score, we developed an easy-to-use web tool for risk scoring as well as therapy stratification in LUAD patients. In summary, we have proposed and validated an ensemble learning model pipeline within the framework of metabolic reprogramming, offering potential insights for LUAD treatment and an effective approach for developing prognostic models for other diseases.

Section: Discussionmentioning

confidence: 99%

Architecting the metabolic reprogramming survival risk framework in LUAD through single-cell landscape analysis: three-stage ensemble learning with genetic algorithm optimization

Sun,

Nong,

Meng

et al. 2024

“…We found immune checkpoint genes (BRAF, ALK, CD276, CD160, TNFSF9, EGFR, CD80, DDR1, ARIH1, TNFSF25, and KRAS) were up-regulated in the high-risk group, which indicated that treatment with anti-immune checkpoint genes therapy may be beneficial for TNBC patients. Furthermore, various computational methods have been applied to drug screening for multiple diseases [52][53][54][55], our research investigated the sensitivity of TNBC patients to common chemotherapeutic drugs. The low-risk group showed heightened sensitivity to cisplatin, suggesting that the SRlncRNA signature could aid in personalized treatment planning for TNBC patients.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of stemness-related lncRNAs in triple-negative breast cancer identified a novel prognostic signature related to treatment outcomes, immune landscape analysis and therapeutic guidance: a silico analysis with in vivo experiments

Zhang,

Wang

et al. 2024

Background Cancer stem cells (CSCs) and long non-coding RNAs (lncRNAs) are known to play a crucial role in the growth, migration, recurrence, and drug resistance of tumor cells, particularly in triple-negative breast cancer (TNBC). This study aims to investigate stemness-related lncRNAs (SRlncRNAs) as potential prognostic indicators for TNBC patients. Methods Utilizing RNA sequencing data and corresponding clinical information from the TCGA database, and employing Weighted Gene Co-expression Network Analysis (WGCNA) on TNBC mRNAsi sourced from an online database, stemness-related genes (SRGs) and SRlncRNAs were identified. A prognostic model was developed using univariate Cox and LASSO-Cox analysis based on SRlncRNAs. The performance of the model was evaluated using Kaplan–Meier analysis, ROC curves, and ROC-AUC. Additionally, the study delved into the underlying signaling pathways and immune status associated with the divergent prognoses of TNBC patients. Results The research identified a signature of six SRlncRNAs (AC245100.6, LINC02511, AC092431.1, FRGCA, EMSLR, and MIR193BHG) for TNBC. Risk scores derived from this signature were found to correlate with the abundance of plasma cells. Furthermore, the nominated chemotherapy drugs for TNBC exhibited considerable variability between different risk score groups. RT-qPCR validation confirmed abnormal expression patterns of these SRlncRNAs in TNBC stem cells, affirming the potential of the SRlncRNAs signature as a prognostic biomarker. Conclusion The identified signature not only demonstrates predictive power in terms of patient outcomes but also provides insights into the underlying biology, signaling pathways, and immune status associated with TNBC prognosis. The findings suggest the possibility of guiding personalized treatments, including immune checkpoint gene therapy and chemotherapy strategies, based on the risk scores derived from the SRlncRNA signature. Overall, this research contributes valuable knowledge towards advancing precision medicine in the context of TNBC.

“…Notably, these AI-powered approaches have significantly reduced the time needed to identify promising drug candidates compared to traditional methods [86][87][88][89][90][91]. Numerous other examples highlight the capacity of AI-based methods to expedite drug screening and discovery [92] and enhance the development of more effective therapies, drug combinations for drug synergies [93,94], and drug repurposing [88,[95][96][97][98][99][100][101][102][103] for various other diseases [104][105][106][107][108][109][110].…”

Section: Examples Of Successful Drug Discovery Efforts Facilitated By Aimentioning

confidence: 99%

Tribulations and future opportunities for artificial intelligence in precision medicine

Carini,

Seyhan

2024

Upon a diagnosis, the clinical team faces two main questions: what treatment, and at what dose? Clinical trials' results provide the basis for guidance and support for official protocols that clinicians use to base their decisions. However, individuals do not consistently demonstrate the reported response from relevant clinical trials. The decision complexity increases with combination treatments where drugs administered together can interact with each other, which is often the case. Additionally, the individual's response to the treatment varies with the changes in their condition. In practice, the drug and the dose selection depend significantly on the medical protocol and the medical team's experience. As such, the results are inherently varied and often suboptimal. Big data and Artificial Intelligence (AI) approaches have emerged as excellent decision-making tools, but multiple challenges limit their application. AI is a rapidly evolving and dynamic field with the potential to revolutionize various aspects of human life. AI has become increasingly crucial in drug discovery and development. AI enhances decision-making across different disciplines, such as medicinal chemistry, molecular and cell biology, pharmacology, pathology, and clinical practice. In addition to these, AI contributes to patient population selection and stratification. The need for AI in healthcare is evident as it aids in enhancing data accuracy and ensuring the quality care necessary for effective patient treatment. AI is pivotal in improving success rates in clinical practice. The increasing significance of AI in drug discovery, development, and clinical trials is underscored by many scientific publications. Despite the numerous advantages of AI, such as enhancing and advancing Precision Medicine (PM) and remote patient monitoring, unlocking its full potential in healthcare requires addressing fundamental concerns. These concerns include data quality, the lack of well-annotated large datasets, data privacy and safety issues, biases in AI algorithms, legal and ethical challenges, and obstacles related to cost and implementation. Nevertheless, integrating AI in clinical medicine will improve diagnostic accuracy and treatment outcomes, contribute to more efficient healthcare delivery, reduce costs, and facilitate better patient experiences, making healthcare more sustainable. This article reviews AI applications in drug development and clinical practice, making healthcare more sustainable, and highlights concerns and limitations in applying AI.