In recent years, cancer genome sequencing and other high-throughput studies of cancer genomes have generated many notable discoveries. In this review, Novel genomic alteration mechanisms, such as chromothripsis (chromosomal crisis) and kataegis (mutation storms), and their implications for cancer are discussed. Genomic alterations spur cancer genome evolution. Thus, the relationship between cancer clonal evolution and cancer stems cells is commented. The key question in cancer biology concerns how these genomic alterations support cancer development and metastasis in the context of biological functioning. Thus far, efforts such as pathway analysis have improved the understanding of the functional contributions of genetic mutations and DNA copy number variations to cancer development, progression and metastasis. However, the known pathways correspond to a small fraction, plausibly 5-10%, of somatic mutations and genes with an altered copy number. To develop a comprehensive understanding of the function of these genomic alterations in cancer, an integrative network framework is proposed and discussed. Finally, the challenges and the directions of studying cancer omic data using an in
Cancer data, particularly cancer incidence and mortality, are fundamental to understand the cancer burden, to set targets for cancer control and to evaluate the evolution of the implementation of a cancer control policy. However, the complexity of data collection, classification, validation and processing result in cancer incidence figures often lagging two to three years behind the calendar year. In response, national or regional population-based cancer registries (PBCRs) are increasingly interested in methods for forecasting cancer incidence. However, in many countries there is an additional difficulty in projecting cancer incidence as regional registries are usually not established in the same year and therefore cancer incidence data series between different regions of a country are not harmonised over time. This study addresses the challenge of forecasting cancer incidence with incomplete data at both regional and national levels. To achieve this, we propose the use of multivariate spatio-temporal shared component models that jointly model mortality data and available cancer incidence data. We evaluate the performance of these multivariate models using lung cancer incidence dat
Recent tumor genome sequencing confirmed that one tumor often consists of multiple cell subpopulations (clones) which bear different, but related, genetic profiles such as mutation and copy number variation profiles. Thus far, one tumor has been viewed as a whole entity in cancer functional studies. With the advances of genome sequencing and computational analysis, we are able to quantify and computationally dissect clones from tumors, and then conduct clone-based analysis. Emerging technologies such as single-cell genome sequencing and RNA-Seq could profile tumor clones. Thus, we should reconsider how to conduct cancer systems biology studies in the genome sequencing era. We will outline new directions for conducting cancer systems biology by considering that genome sequencing technology can be used for dissecting, quantifying and genetically characterizing clones from tumors. Topics discussed in Part 1 of this review include computationally quantifying of tumor subpopulations; clone-based network modeling, cancer hallmark-based networks and their high-order rewiring principles and the principles of cell survival networks of fast-growing clones.
Nanorobots are a promising development in targeted drug delivery and the treatment of neurological disorders, with potential for crossing the blood-brain barrier (BBB). These small devices leverage advancements in nanotechnology and bioengineering for precise navigation and targeted payload delivery, particularly for conditions like brain tumors, Alzheimer's disease, and Parkinson's disease. Recent progress in artificial intelligence (AI) and machine learning (ML) has improved the navigation and effectiveness of nanorobots, allowing them to detect and interact with cancer cells through biomarker analysis. This study presents a new reinforcement learning (RL) framework for optimizing nanorobot navigation in complex biological environments, focusing on cancer cell detection by analyzing the concentration gradients of surrounding biomarkers. We utilize a computer simulation model to explore the behavior of nanorobots in a three-dimensional space with cancer cells and biological barriers. The proposed method uses Q-learning to refine movement strategies based on real-time biomarker concentration data, enabling nanorobots to autonomously navigate to cancerous tissues for targeted drug d
Prostate cancer (PCa) is the most prevalent cancer among men in the United States, accounting for nearly 300,000 cases, 29\% of all diagnoses and 35,000 total deaths in 2024. Traditional screening methods such as prostate-specific antigen (PSA) testing and magnetic resonance imaging (MRI) have been pivotal in diagnosis, but have faced limitations in specificity and generalizability. In this paper, we explore the potential of enhancing PCa gland segmentation using a novel MRI modality called synthetic correlated diffusion imaging (CDI$^s$). We employ several state-of-the-art deep learning models, including U-Net, SegResNet, Swin UNETR, Attention U-Net, and LightM-UNet, to segment prostate glands from a 200 CDI$^s$ patient cohort. We find that SegResNet achieved superior segmentation performance with a Dice-Sorensen coefficient (DSC) of $76.68 \pm 0.8$. Notably, the Attention U-Net, while slightly less accurate (DSC $74.82 \pm 2.0$), offered a favorable balance between accuracy and computational efficiency. Our findings demonstrate the potential of deep learning models in improving prostate gland segmentation using CDI$^s$ to enhance PCa management and clinical support.
We present a general computational theory of cancer and its developmental dynamics. The theory is based on a theory of the architecture and function of developmental control networks which guide the formation of multicellular organisms. Cancer networks are special cases of developmental control networks. Cancer results from transformations of normal developmental networks. Our theory generates a natural classification of all possible cancers based on their network architecture. Each cancer network has a unique topology and semantics and developmental dynamics that result in distinct clinical tumor phenotypes. We apply this new theory with a series of proof of concept cases for all the basic cancer types. These cases have been computationally modeled, their behavior simulated and mathematically described using a multicellular systems biology approach. There are fascinating correspondences between the dynamic developmental phenotype of computationally modeled {\em in silico} cancers and natural {\em in vivo} cancers. The theory lays the foundation for a new research paradigm for understanding and investigating cancer. The theory of cancer networks implies that new diagnostic methods
Tumor protein P53 is believed to be involved in over half of human cancers cases, the prediction of malignancies plays essential roles not only in advance detection for cancer, but also in discovering effective prevention and treatment of cancer, till now there isn't approach be able in prediction the mutated in tumor protein P53 which is caused high ratio of human cancers like breast, Blood, skin, liver, lung, bladder etc. This research proposed a new approach for prediction pre-cancer via detection malignant mutations in tumor protein P53 using bioinformatics tools like FASTA, BLAST, CLUSTALW and TP53 databases worldwide. Implement and apply this new approach of prediction pre-cancer through mutations at tumor protein P53 shows an effective result when used more specific parameters/features to extract the prediction result that means when the user increase the number of filters of the results which obtained from the database gives more specific diagnosis and classify, addition that the detecting pre-cancer via prediction mutated tumor protein P53 will reduces a person's cancers in the future by avoiding exposure to toxins, radiation or monitoring themselves at older ages by chang
With the advances in artificial intelligence (AI), data-driven algorithms are becoming increasingly popular in the medical domain. However, due to the nonlinear and complex behavior of many of these algorithms, decision-making by such algorithms is not trustworthy for clinicians and is considered a black-box process. Hence, the scientific community has introduced explainable artificial intelligence (XAI) to remedy the problem. This systematic scoping review investigates the application of XAI in breast cancer detection and risk prediction. We conducted a comprehensive search on Scopus, IEEE Explore, PubMed, and Google Scholar (first 50 citations) using a systematic search strategy. The search spanned from January 2017 to July 2023, focusing on peer-reviewed studies implementing XAI methods in breast cancer datasets. Thirty studies met our inclusion criteria and were included in the analysis. The results revealed that SHapley Additive exPlanations (SHAP) is the top model-agnostic XAI technique in breast cancer research in terms of usage, explaining the model prediction results, diagnosis and classification of biomarkers, and prognosis and survival analysis. Additionally, the SHAP mo
A tumor often consists of multiple cell subpopulations (clones). Current chemo-treatments often target one clone of a tumor. Although the drug kills that clone, other clones overtake it and the tumor reoccurs. Genome sequencing and computational analysis allows to computational dissection of clones from tumors, while singe-cell genome sequencing including RNA-Seq allows to profiling of these clones. This opens a new window for treating a tumor as a system in which clones are evolving. Future cancer systems biology studies should consider a tumor as an evolving system with multiple clones. Therefore, topics discussed in Part 2 of this review include evolutionary dynamics of clonal networks, early-warning signals for formation of fast-growing clones, dissecting tumor heterogeneity, and modeling of clone-clone-stroma interactions for drug resistance. The ultimate goal of the future systems biology analysis is to obtain a whole-system understanding of a tumor and therefore provides a more efficient and personalized management strategies for cancer patients.
Environmental and genetic mutations can transform the cells in a co-operating healthy tissue into an ecosystem of individualistic tumour cells that compete for space and resources. Various selection forces are responsible for driving the evolution of cells in a tumour towards more malignant and aggressive phenotypes that tend to have a fitness advantage over the older populations. Although the evolutionary nature of cancer has been recognised for more than three decades (ever since the seminal work of Nowell) it has been only recently that tools traditionally used by ecological and evolutionary researchers have been adopted to study the evolution of cancer phenotypes in populations of individuals capable of co-operation and competition. In this chapter we will describe game theory as an important tool to study the emergence of cell phenotypes in a tumour and will critically review some of its applications in cancer research. These applications demonstrate that game theory can be used to understand the dynamics of somatic cancer evolution and suggest new therapies in which this knowledge could be applied to gain some control over the evolution of the tumour.
Background Precise prediction of cancer types is vital for cancer diagnosis and therapy. Important cancer marker genes can be inferred through predictive model. Several studies have attempted to build machine learning models for this task however none has taken into consideration the effects of tissue of origin that can potentially bias the identification of cancer markers. Results In this paper, we introduced several Convolutional Neural Network (CNN) models that take unstructured gene expression inputs to classify tumor and non-tumor samples into their designated cancer types or as normal. Based on different designs of gene embeddings and convolution schemes, we implemented three CNN models: 1D-CNN, 2D-Vanilla-CNN, and 2D-Hybrid-CNN. The models were trained and tested on combined 10,340 samples of 33 cancer types and 731 matched normal tissues of The Cancer Genome Atlas (TCGA). Our models achieved excellent prediction accuracies (93.9-95.0%) among 34 classes (33 cancers and normal). Furthermore, we interpreted one of the models, known as 1D-CNN model, with a guided saliency technique and identified a total of 2,090 cancer markers (108 per class). The concordance of differential e
In modern collider experiments, the quest to explore fundamental interactions between elementary particles has reached unparalleled levels of precision. Signatures from particle physics detectors are low-level objects (such as energy depositions or tracks) encoding the physics of collisions (the final state particles of hard scattering interactions). The complete simulation of them in a detector is a computational and storage-intensive task. To address this computational bottleneck in particle physics, alternative approaches have been developed, introducing additional assumptions and trade off accuracy for speed.The field has seen a surge in interest in surrogate modeling the detector simulation, fueled by the advancements in deep generative models. These models aim to generate responses that are statistically identical to the observed data. In this paper, we conduct a comprehensive and exhaustive taxonomic review of the existing literature on the simulation of detector signatures from both methodological and application-wise perspectives. Initially, we formulate the problem of detector signature simulation and discuss its different variations that can be unified. Next, we classify
This study focuses on comparing deep learning methods for the segmentation and quantification of uncertainty in prostate segmentation from MRI images. The aim is to improve the workflow of prostate cancer detection and diagnosis. Seven different U-Net-based architectures, augmented with Monte-Carlo dropout, are evaluated for automatic segmentation of the central zone, peripheral zone, transition zone, and tumor, with uncertainty estimation. The top-performing model in this study is the Attention R2U-Net, achieving a mean Intersection over Union (IoU) of 76.3% and Dice Similarity Coefficient (DSC) of 85% for segmenting all zones. Additionally, Attention R2U-Net exhibits the lowest uncertainty values, particularly in the boundaries of the transition zone and tumor, when compared to the other models.
In this article, I put forward the idea that the neoplastic process (NP) has deep evolutionary roots and make specific predictions about the connection between cancer and the formation of the first embryo, which allowed for the evolutionary radiation of metazoans. My main hypothesis is that the NP is at the heart of cellular mechanisms responsible for animal morphogenesis and, given its embryological basis, also at the center of animal evolution. It is thus understood that NP-associated mechanisms are deeply rooted in evolutionary history and tied to the formation of the first animal embryo. In my consideration of these arguments, I expound on how cancer biology is perfectly intertwined with evolutionary biology. I describe essential cellular components of unicellular holozoans that served as a basis for the formation of the neoplastic functional module (NFM) and its subsequent exaptation, which brought forth two great biophysical revolutions within the first embryo. Finally, I examine the role of Physics in the modeling of the NFM and its contribution to morphogenesis to reveal the totipotency of the zygote.
There is a widening recognition that cancer cells are products of complex developmental processes. Carcinogenesis and metastasis formation are increasingly described as systems-level, network phenomena. Here we propose that malignant transformation is a two-phase process, where an initial increase of system plasticity is followed by a decrease of plasticity at late stages of carcinogenesis as a model of cellular learning. We describe the hallmarks of increased system plasticity of early, tumor initiating cells, such as increased noise, entropy, conformational and phenotypic plasticity, physical deformability, cell heterogeneity and network rearrangements. Finally, we argue that the large structural changes of molecular networks during cancer development necessitate a rather different targeting strategy in early and late phase of carcinogenesis. Plastic networks of early phase cancer development need a central hit, while rigid networks of late stage primary tumors or established metastases should be attacked by the network influence strategy, such as by edgetic, multi-target, or allo-network drugs. Cancer stem cells need special diagnosis and targeting, since their dormant and rapid
The integration of power electronics-based energy storage systems (PEESs) into power systems introduces potential instabilities. This study reviews efforts in dynamic analysis of both AC and DC power systems integrated with PEESs, covering dynamic modeling, analysis methods, and potential instability risks. Major conclusions are drawn as: 1) Simplified models of PEESs have been widely used for dynamic analysis of power systems. However, it may cause "error aggregation" as the scale of PEESs increases, leading to mistakes in results, which induces significant concerns. 2) Traditional stability mechanism analysis methods remain effective for single grid-connected PEES and large-scale PEESs with parallel and series connections. However, they are inadequate for PEESs with distributed connections. To fill in this gap, an idea of mechanism analysis based on "dynamic reconstruction" is proposed. 3) Potential instability risks caused by PEESs integration may differ from those caused by renewable energy integration due to differences in functional controls and bidirectional power flow. However, comprehensive investigations in this regard are lacking and require significant attention. To ens
This paper proposes a new methodology to automatically build semantic hierarchies suitable for image annotation and classification. The building of the hierarchy is based on a new measure of semantic similarity. The proposed measure incorporates several sources of information: visual, conceptual and contextual as we defined in this paper. The aim is to provide a measure that best represents image semantics. We then propose rules based on this measure, for the building of the final hierarchy, and which explicitly encode hierarchical relationships between different concepts. Therefore, the built hierarchy is used in a semantic hierarchical classification framework for image annotation. Our experiments and results show that the hierarchy built improves classification results. Ce papier propose une nouvelle methode pour la construction automatique de hierarchies semantiques adaptees a la classification et a l'annotation d'images. La construction de la hierarchie est basee sur une nouvelle mesure de similarite semantique qui integre plusieurs sources d'informations: visuelle, conceptuelle et contextuelle que nous definissons dans ce papier. L'objectif est de fournir une mesure qui est p
There are various algorithms and methodologies used for automated screening of cervical cancer by segmenting and classifying cervical cancer cells into different categories. This study presents a critical review of different research papers published that integrated AI methods in screening cervical cancer via different approaches analyzed in terms of typical metrics like dataset size, drawbacks, accuracy etc. An attempt has been made to furnish the reader with an insight of Machine Learning algorithms like SVM (Support Vector Machines), GLCM (Gray Level Co-occurrence Matrix), k-NN (k-Nearest Neighbours), MARS (Multivariate Adaptive Regression Splines), CNNs (Convolutional Neural Networks), spatial fuzzy clustering algorithms, PNNs (Probabilistic Neural Networks), Genetic Algorithm, RFT (Random Forest Trees), C5.0, CART (Classification and Regression Trees) and Hierarchical clustering algorithm for feature extraction, cell segmentation and classification. This paper also covers the publicly available datasets related to cervical cancer. It presents a holistic review on the computational methods that have evolved over the period of time, in chronological order in detection of maligna
Correlated electron systems are among the centerpieces of modern condensed matter sciences, where many interesting physical phenomena, such as metal-insulator transition and high-Tc superconductivity appear. Recent efforts have been focused on electrostatic doping of such materials to probe the underlying physics without introducing disorder as well as to build field-effect transistors that may complement conventional semiconductor metal-oxide-semiconductor field effect transistor (MOSFET) technology. This review focuses on metal-insulator transition mechanisms in correlated electron materials and three-terminal field effect devices utilizing such correlated oxides as the channel layer. We first describe how electron-disorder interaction, electron-phonon interaction and/or electron correlation in solids could modify the electronic properties of materials and lead to metal-insulator transitions. Then we analyze experimental efforts toward utilizing these transitions in field effect transistors and their underlying principles. It is pointed out that correlated electron systems show promise among these various materials displaying phase transitions for logic technologies. Furthermore,
Cancer is increasingly perceived as a systems-level, network phenomenon. The major trend of malignant transformation can be described as a two-phase process, where an initial increase of network plasticity is followed by a decrease of plasticity at late stages of tumor development. The fluctuating intensity of stress factors, like hypoxia, inflammation and the either cooperative or hostile interactions of tumor inter-cellular networks, all increase the adaptation potential of cancer cells. This may lead to the bypass of cellular senescence, and to the development of cancer stem cells. We propose that the central tenet of cancer stem cell definition lies exactly in the indefinability of cancer stem cells. Actual properties of cancer stem cells depend on the individual "stress-history" of the given tumor. Cancer stem cells are characterized by an extremely large evolvability (i.e. a capacity to generate heritable phenotypic variation), which corresponds well with the defining hallmarks of cancer stem cells: the possession of the capacity to self-renew and to repeatedly re-build the heterogeneous lineages of cancer cells that comprise a tumor in new environments. Cancer stem cells rep