搜索结果：Annual review of cancer biology

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.

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.

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

This technical monograph provides a comprehensive overview of the field of quantum biology. It approaches quantum biology from a physical perspective with core quantum mechanical concepts presented foremost to provide a theoretical foundation for the field. An extensive body of research is covered to clarify the significance of quantum biology as a scientific field, outlining the field's long-standing importance in the historical development of quantum theory. This lays the essential groundwork to enable further advances in nanomedicine and biotechnology. Written for academics, biological science researchers, physicists, biochemists, medical technologists, and students of quantum mechanics, this text brings clarity to fundamental advances being made in the emerging science of quantum biology.

Understanding the biological mechanisms of disease is crucial for medicine, and in particular, for drug discovery. AI-powered analysis of genome-scale biological data holds great potential in this regard. The increasing availability of single-cell RNA sequencing data has enabled the development of large foundation models for disease biology. However, existing foundation models only modestly improve over task-specific models in downstream applications. Here, we explored two avenues for improving single-cell foundation models. First, we scaled the pre-training data to a diverse collection of 116 million cells, which is larger than those used by previous models. Second, we leveraged the availability of large-scale biological annotations as a form of supervision during pre-training. We trained the \model family of models comprising six transformer-based state-of-the-art single-cell foundation models with 70 million, 160 million, and 400 million parameters. We vetted our models on several downstream evaluation tasks, including identifying the underlying disease state of held-out donors not seen during training, distinguishing between diseased and healthy cells for disease conditions and

Spatially annotated single-cell datasets provide unprecedented opportunities to dissect cell-cell communication in development and disease. Heterotypic signaling includes interactions between different cell types and is well established in tissue development and spatial organization. Epithelial organization requires several different programs that are tightly regulated. Planar cell polarity is the organization of epithelial cells along the planar axis orthogonal to the apical-basal axis. In this study, we investigate planar cell polarity factors and explore the implications of developmental regulators as malignant drivers. Utilizing cancer systems biology analysis, we derive gene expression network for WNT-ligands (WNT) and their cognate frizzled (FZD) receptors in skin cutaneous melanoma. The profiles supported by unsupervised clustering of multiple-sequence alignments identify ligand-independent signaling and implications for metastatic progression based on the underpinning developmental spatial program. Omics studies and spatial biology connect developmental programs with oncological events and explain key spatial features of metastatic aggressiveness. Dysregulation of prominent

Direct detection experiments, which are designed to detect the scattering of dark matter off nuclei in detectors, are a critical component in the search for the Universe's missing matter. The count rate in these experiments should experience an annual modulation due to the relative motion of the Earth around the Sun. This modulation, not present for most known background sources, is critical for solidifying the origin of a potential signal as dark matter. In this article, we review the physics of annual modulation, discussing the practical formulae needed to interpret a modulating signal. We focus on how the modulation spectrum changes depending on the particle and astrophysics models for the dark matter. For standard assumptions, the count rate has a cosine dependence with time, with a maximum in June and a minimum in December. Well-motivated generalizations of these models, however, can affect both the phase and amplitude of the modulation. We show how a measurement of an annually modulating signal could teach us about the presence of substructure in the Galactic halo or about the interactions between dark and baryonic matter. Although primarily a theoretical review, we briefly d

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

Embryology has long played a foundational role in shaping our scientific understanding of animal evolution. In recent decades, growing evidence has also highlighted its role in cancer. Despite the indisputable similarities between embryonic development and cancer, there has been limited discussion on the profound embryological implications for the disease. This article explores the understanding of cancer as an embryological and evolutionary phenomenon, offering a fresh perspective on the disease and discussing immediate consequences in the search for therapeutic approaches

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.

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

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.

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

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

A review of the Annual Review of Astronomy and Astrophysics Volume 52, 2014 (Ed. S.M. Faber, Ewine van Dishoeck, and John Kormendy) is given, with a perspective of understanding the current trends in Astronomy and Astrophysics. The impact of high volume data, high connectivity, and fast computations is clearly seen in the various research areas discussed in this volume. This has provided unprecedented development in the understanding of various astrophysical phenomena. At the same time, some negative trends like commodification of science, ignoring dissenting views are also evident.

Recently, there has been great interest in developing Artificial Intelligence (AI) enabled computer-aided diagnostics solutions for the diagnosis of skin cancer. With the increasing incidence of skin cancers, low awareness among a growing population, and a lack of adequate clinical expertise and services, there is an immediate need for AI systems to assist clinicians in this domain. A large number of skin lesion datasets are available publicly, and researchers have developed AI-based image classification solutions, particularly deep learning algorithms, to distinguish malignant skin lesions from benign lesions in different image modalities such as dermoscopic, clinical, and histopathology images. Despite the various claims of AI systems achieving higher accuracy than dermatologists in the classification of different skin lesions, these AI systems are still in the very early stages of clinical application in terms of being ready to aid clinicians in the diagnosis of skin cancers. In this review, we discuss advancements in the digital image-based AI solutions for the diagnosis of skin cancer, along with some challenges and future opportunities to improve these AI systems to support d

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

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. They are involved in key biological processes and then may play a major role in the development of human diseases including cancer, in particular their involvement in breast cancer metastasis has been confirmed. Recently, the authors of ref.(\cite{key1} have found that miR-429 may have a role in the inhibition of breast cancer metastasis and have identified its target gene CRKL as a potential candidate. In this paper, by using systems biology tools we have shown that CRKL is involved in positive regulation of ERK1/2 signaling pathway and contribute to the regulation of LYN through a topological generalization of feed forward loop.

This article frames the relation between biology and physics by characterizing the former as a subdiscipline rather than a special case of the latter. To do this, we posit biological physics as the science of living matter in contrast to classic biophysics, the study of organismal properties by physical techniques. At the scale of the individual cell, living matter is nonunitary, i.e., not composed of aggregated subunits, and has features (e.g., intracellular organizational arrangements and biomolecular condensates) that are unlike any materials of the nonliving world. In transiently or constitutively multicellular forms (social microorganisms, animals, plants), living matter sustains physical processes that are generic (shared with nonliving matter, e.g., subunit communication by molecular diffusion in cellular slime molds), biogeneric (analogous to nonliving matter but realized through cellular activities, e.g., subunit demixing in animal embryos) or nongeneric (pertaining to sui generis materials, e.g., budding of active solids in plants). This "forms of matter" perspective is philosophically situated in the dialectical materialism of Engels and Hessen and the multilevel physica