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QuantAnts machines discover biomarkers for RAS signaling activation and design sgRNAs for CRISPR to target complex CD9, CD34, and CD74.

Nam Nguyen

Published Dec 6, 2022• 0 citations
Publisher

Abstract

Abstract In this work, we introduce a quantum algorithm for biomarker identification in oncology, named QuantAnts machines, pronounced "quantant machine." Our proposed machine intelligence allows sampling biomarker-verse for the targeted RAS signaling activation, revealing combinations of biomarkers with therapeutic applications. Notable, the QuantAnts for Clinical Oncology model, ASCO(ant-4) discovers the complex CD9, CD34, and CD74 as targeting for RAS pathway for some cancer phenotypes such as gastric, colorectal (with/without metastasis), ovarian, breast and brain cancer. To the end, we show the generalization of QuantAnts machines by altering the model for genetic code designs (named QuantAnts-CRISPR), which enabling optimized sgRNA for CRISPR-Cas9 to target the complex CD9, CD34, and CD74 all-together. The found sgRNA designs are optimized by reversing mutation processes over the targeted complex, i.e., balancing the mutated contents over the input biomarker-verse.

DOI
10.21203/rs.3.rs-2347890/v1

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Abstract In this work, we introduce a quantum algorithm for biomarker identification in oncology, named QuantAnts machines, pronounced "quantant machine." Our proposed machine intelligence allows sampling biomarker-verse for the targeted RAS signaling activation, revealing combinations of biomarkers with therapeutic applications. Notable, the QuantAnts for Clinical Oncology model, ASCO(ant-4) discovers the complex CD9, CD34, and CD74 as targeting for RAS pathway for some cancer phenotypes such as gastric, colorectal (with/without metastasis), ovarian, breast and brain cancer. To the end, we show the generalization of QuantAnts machines by altering the model for genetic code designs (named QuantAnts-CRISPR), which enabling optimized sgRNA for CRISPR-Cas9 to target the complex CD9, CD34, and CD74 all-together. The found sgRNA designs are optimized by reversing mutation processes over the targeted complex, i.e., balancing the mutated contents over the input biomarker-verse.
The discovery of biomarker sets for a targeted pathway is a challenging problem in biomedical medicine, which is computationally prohibited on classical algorithms due to the massive search space. Here, I present a quantum algorithm named QuantAnts Machine to address the task. The proposed algorithm is a quantum analog of the classical Ant Colony Optimization (ACO). We create the mixture of multi-domain from genetic networks by representation theory, enabling the search of biomarkers from the multi-modality of the human genome. Although the proposed model can be generalized, we investigate the RAS-mutational activation in this work. To the end, QuantAnts Machine discovers rarely-known biomarkers in clinical-associated domain for RAS-activation pathway, including COL5A1, COL5A2, CCT5, MTSS1 and NCAPD2. Besides, the model also suggests several therapeutic-targets such as JUP, CD9, CD34 and CD74.
Quantum machine learning offers a promising new paradigm for computational biology by leveraging quantum mechanical principles to enhance cancer classification, biomarker discovery, and bioinformatics diagnostics. In this study, we apply QML to identify subtype specific biomarkers for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two predominant forms of non-small cell lung cancer. Our methodology involves a two-phase process: in Phase 1, differential expression analysis and methylation analysis between tumor and normal samples allows us to identify LUAD-specific and LUSC-specific genes, revealing potential prognostic biomarkers for cancer subtypes. Phase 2 focuses on developing a quantum classifier capable of distinguishing between LUAD and LUSC tumors, as well as between tumor and normal samples. This classifier not only enhances diagnostic precision but also demonstrates the quantum advantage in processing large-scale multiomic datasets. Our results consistently demonstrated that Sample3, representing the combined gene set, achieved the highest overall predictive performance in all metrics. These results demonstrate that QML provides an effective and scalable approach for biomarker discovery and subtype specific cancer classification. GO enrichment analysis highlighted the significant involvement of genes in synaptic signaling, ion channel regulation, and neuronal development. In the quantum phase, KEGG analysis further identified enrichment in cancer-associated pathways, including neurotrophin, MAPK, Ras, and PI3KAkt signaling, with key genes such as NGFR, NTRK2, and NTF3 suggesting a central role in neurotrophinmediated oncogenic processes. Our findings highlight the growing potential of quantum computing to advance precision oncology and next-generation biomedical analytics.
BACKGROUND: Biomarker discovery is a challenging task due to the massive search space. Quantum computing and quantum Artificial Intelligence (quantum AI) can be used to address the computational problem of biomarker discovery from genetic data. METHOD: We propose a Quantum Neural Networks architecture to discover genetic biomarkers for input activation pathways. The Maximum Relevance-Minimum Redundancy criteria score biomarker candidate sets. Our proposed model is economical since the neural solution can be delivered on constrained hardware. RESULTS: We demonstrate the proof of concept on four activation pathways associated with CTLA4, including (1) CTLA4-activation stand-alone, (2) CTLA4-CD8A-CD8B co-activation, (3) CTLA4-CD2 co-activation, and (4) CTLA4-CD2-CD48-CD53-CD58-CD84 co-activation. CONCLUSION: The model indicates new genetic biomarkers associated with the mutational activation of CLTA4-associated pathways, including 20 genes: CLIC4, CPE, ETS2, FAM107A, GPR116, HYOU1, LCN2, MACF1, MT1G, NAPA, NDUFS5, PAK1, PFN1, PGAP3, PPM1G, PSMD8, RNF213, SLC25A3, UBA1, and WLS. We open source the implementation at: https://github.com/namnguyen0510/Biomarker-Discovery-with-Quantum-Neural-Networks .
This research project presents a PRISMA-guided systematic literature review exploring the application of quantum machine learning (QML) in oncology, a rapidly growing field with fragmented evidence. The study synthesizes peer-reviewed studies from six databases (ACM, IEEE, MDPI, Scopus, Wiley, and PubMed) published between 2020 and 2026, screening 212 records and selecting 49 studies for analysis. The review examines clinical tasks, cancer domains, QML architectures, challenges, and future directions, revealing that current research mainly focuses on classification and detection, particularly in breast cancer and brain tumors, using hybrid quantum-classical models. Despite promising results, progress is limited by hardware constraints, simulator dependence, and insufficient clinical validation. The findings provide a clear overview of current QML trends and highlight future priorities, including real quantum hardware testing, diverse clinical datasets, standardized benchmarking, and stronger collaboration between computing and oncology communities.
Quantum machine learning (QML) presents novel opportunities for resolving, accelerating, and refining computational biology challenges. In biomedical research and personalized medicine, multi-omics integration offers a comprehensive understanding of complex biological systems, bridging the gap between basic research and clinical applications. Recent advancements in quantum computing could enhance multi-omics integration by leveraging unique quantum principles, potentially revealing intricate patterns in multi-omics datasets and offering new insights into the molecular landscape of lung cancer. This study focuses on the integration, feature selection, diagnostic classification, and biomarker identification of lung cancer types-LUAD primary tumor and solid tissue normal-using QML. Given the heterogeneity and high dimensionality of the data, we aim to assess the performance of QML in feature selection, reduction, encoding, and diagnostic classification in integrated multi-omics cancer datasets. We demonstrate the efficacy of Quantum Neural Networks (QNNs) for classifying multi-omics lung cancer data from The Cancer Genome Atlas, comparing our framework with 16 and 64 dimensions of feature using QML. Our results show that the Multi-omic Quantum Machine Learning (MQML) framework achieves superior classification performance with smaller training datasets, as determined by significant and non-significant p-values. This study provides empirical evidence for the potential application of unconventional computing approaches in biomed-ical sciences, particularly in oncology research, including cancer subtype diagnostic, survival, and stage classification. Key results include the identification of sixteen genes and thirty-two genes with the hybrid quantum-classical neural net-work model, with notable genes such as MIR632, CYP19A1, RP11-108K3.1, C14orf39, THUMPD1, ACSM3, GSC, MIR92a-2, DYRK1B, DNAJA1, IRX1, FMR1, POU2F2, MIR9-2, ZNF274, MIR196a-1, MIR3653, MIR33b, MIR301a, MIR182, MIR520a, PYGO2, EMX2OS, EMX2, RP11-550F7.1, RPS11, MIR20a, EIF4G2, IGLV1-47, RP11-180M15.7, SCYL3, AC107081.5, C2orf47, FST, MIR7-1, SLC22A18, CLDN5, and AC007879.7 identified as having significant and non-significant p-values asso-ciated with LUAD patient predictions.
Mutations in the TP53 gene are among the most prevalent alterations in human cancers and are known to influence therapeutic responses. Accurate prediction of drug sensitivity based on TP53 mutation profiles remains a major challenge in precision oncology. In this study, we propose a quantum-enhanced framework for genomic classification using Quantum Boltzmann Machines (QBMs) applied to quantum-encoded DNA sequences. Exon 5–8 fragments of TP53 containing both wild-type and clinically relevant mutations were encoded using angle-based quantum rotations and input into a QBM architecture trained to predict binary drug response (sensitive vs resistant) based on half-maximal inhibitory concentration (IC50) thresholds. Simulated results demonstrate that the QBM achieved over 91%\mathbf{9 1 \%}91% accuracy in classifying drug sensitivity, outperforming classical Boltzmann models and revealing interpretable latent features. This work showcases the potential of QBMs in modeling sequence-driven phenotypes and supports their application in biomarker discovery, drug response prediction, and quantum-enabled precision medicine.