搜索结果：Journal of molecular biology

The understanding of molecular cell biology requires insight into the structure and dynamics of networks that are made up of thousands of interacting molecules of DNA, RNA, proteins, metabolites, and other components. One of the central goals of systems biology is the unraveling of the as yet poorly characterized complex web of interactions among these components. This work is made harder by the fact that new species and interactions are continuously discovered in experimental work, necessitating the development of adaptive and fast algorithms for network construction and updating. Thus, the "reverse-engineering" of networks from data has emerged as one of the central concern of systems biology research. A variety of reverse-engineering methods have been developed, based on tools from statistics, machine learning, and other mathematical domains. In order to effectively use these methods, it is essential to develop an understanding of the fundamental characteristics of these algorithms. With that in mind, this chapter is dedicated to the reverse-engineering of biological systems. Specifically, we focus our attention on a particular class of methods for reverse-engineering, namely th

Achieving complete reproducibility in science, particularly in research fields such as biodiversity, is challenging due to analytical choices, bias and interpretation. Here, we examine examples of reproducibility in biological systematics, ecology, and molecular biology. To mitigate the impact of interpretation and analytical choices, Artificial Intelligence (AI) has provided potential tools. In the present work, while emphasizing the need for methodological rigor and transparency, we acknowledge the role of interpretation in activities such as coding biological characters and detecting morphological patterns in nature. We explore the opportunities and limitations associated with the synergy between big data and AI in molecular biology, emphasizing the need for a more comprehensive and integrated approach based on dataset quality and usefulness. We conclude by advocating for AI-based tools to assist biologists, reinforcing consilience as a criterion for scientific validity without hindering scientific progress.

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

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.

Using the Scopus dataset (1996-2007) a grand matrix of aggregated journal-journal citations was constructed. This matrix can be compared in terms of the network structures with the matrix contained in the Journal Citation Reports (JCR) of the Institute of Scientific Information (ISI). Since the Scopus database contains a larger number of journals and covers also the humanities, one would expect richer maps. However, the matrix is in this case sparser than in the case of the ISI data. This is due to (i) the larger number of journals covered by Scopus and (ii) the historical record of citations older than ten years contained in the ISI database. When the data is highly structured, as in the case of large journals, the maps are comparable, although one may have to vary a threshold (because of the differences in densities). In the case of interdisciplinary journals and journals in the social sciences and humanities, the new database does not add a lot to what is possible with the ISI databases.

A number of journal classification systems have been developed in bibliometrics since the launch of the Citation Indices by the Institute of Scientific Information (ISI) in the 1960s. These systems are used to normalize citation counts with respect to field-specific citation patterns. The best known system is the so-called "Web-of-Science Subject Categories" (WCs). In other systems papers are classified by algorithmic solutions. Using the Journal Citation Reports 2014 of the Science Citation Index and the Social Science Citation Index (n of journals = 11,149), we examine options for developing a new system based on journal classifications into subject categories using aggregated journal-journal citation data. Combining routines in VOSviewer and Pajek, a tree-like classification is developed. At each level one can generate a map of science for all the journals subsumed under a category. Nine major fields are distinguished at the top level. Further decomposition of the social sciences is pursued for the sake of example with a focus on journals in information science (LIS) and science studies (STS). The new classification system improves on alternative options by avoiding the problem

A review of the mechanisms of speciation is performed. The mechanisms of the evolution of species, taking into account the feedback of the state of the environment and mechanisms of the emergence of complexity, are considered. It is shown that these mechanisms, at the molecular level, cannot work steadily in terms of classical mechanics. Quantum mechanisms of changes in the genome, based on the long-range interaction potential between biologically important molecules, are proposed as one of possible explanation. Different variants of interactions of the organism and environment based on molecular recognition and leading to new species origins are considered. Experiments to verify the model are proposed. This bio-physical study is completed by the general operational model of based on quantum information theory. The latter is applied to model epigenetic evolution.

Some astrobiological models suggest that molecular clouds may serve as habitats for extraterrestrial life. This study reviews recent theoretical work addressing the physical and biochemical prerequisites for life in such environments, with particular focus on three subjects: (1) bioenergetic pathways under extreme low-temperature conditions; (2) the emergence and preservation of biomolecular chirality; and (3) detection methodologies for potential biosignatures. In this paper, we formally introduce the molecular cloud biology concept, which integrates all physicochemical and metabolic processes hypothesized to sustain life within molecular clouds. As a potential branch of astrobiology, molecular cloud biology warrants interdisciplinary collaborative research to validate its foundational assumptions and explore its scientific implications.

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

Using "Analyze Results" at the Web of Science, one can directly generate overlays onto global journal maps of science. The maps are based on the 10,000+ journals contained in the Journal Citation Reports (JCR) of the Science and Social Science Citation Indices (2011). The disciplinary diversity of the retrieval is measured in terms of Rao-Stirling's "quadratic entropy." Since this indicator of interdisciplinarity is normalized between zero and one, the interdisciplinarity can be compared among document sets and across years, cited or citing. The colors used for the overlays are based on Blondel et al.'s (2008) community-finding algorithms operating on the relations journals included in JCRs. The results can be exported from VOSViewer with different options such as proportional labels, heat maps, or cluster density maps. The maps can also be web-started and/or animated (e.g., using PowerPoint). The "citing" dimension of the aggregated journal-journal citation matrix was found to provide a more comprehensive description than the matrix based on the cited archive. The relations between local and global maps and their different functions in studying the sciences in terms of journal lit

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.

Synthetic biology aims at designing modular genetic circuits that can be assembled according to the desired function. When embedded in a cell, a circuit module becomes a small subnetwork within a larger environmental network, and its dynamics is therefore affected by potentially unknown interactions with the environment. It is well-known that the presence of the environment not only causes extrinsic noise but also memory effects, which means that the dynamics of the subnetwork is affected by its past states via a memory function that is characteristic of the environment. We study several generic scenarios for the coupling between a small module and a larger environment, with the environment consisting of a chain of mono-molecular reactions. By mapping the dynamics of this coupled system onto random walks, we are able to give exact analytical expressions for the arising memory functions. Hence, our results give insights into the possible types of memory functions and thereby help to better predict subnetwork dynamics.

Numerous biological functions-such as enzymatic catalysis, the immune response system, and the DNA-protein regulatory network-rely on the ability of molecules to specifically recognize target molecules within a large pool of similar competitors in a noisy biochemical environment. Using the basic framework of signal detection theory, we treat the molecular recognition process as a signal detection problem and examine its overall performance. Thus, we evaluate the optimal properties of a molecular recognizer in the presence of competition and noise. Our analysis reveals that the optimal design undergoes a "phase transition" as the structural properties of the molecules and interaction energies between them vary. In one phase, the recognizer should be complementary in structure to its target (like a lock and a key), while in the other, conformational changes upon binding, which often accompany molecular recognition, enhance recognition quality. Using this framework, the abundance of conformational changes may be explained as a result of increasing the fitness of the recognizer. Furthermore, this analysis may be used in future design of artificial signal processing devices based on bio

The sampling of scale-free networks in Molecular Biology is usually achieved by growing networks from a seed using recursive algorithms with elementary moves which include the addition and deletion of nodes and bonds. These algorithms include the Barabasi-Albert algorithm. Later algorithms, such as the Duplication-Divergence algorithm, the Solé algorithm and the iSite algorithm, were inspired by biological processes underlying the evolution of protein networks, and the networks they produce differ essentially from networks grown by the Barabasi-Albert algorithm. In this paper the mean field analysis of these algorithms is reconsidered, and extended to variant and modified implementations of the algorithms. The degree sequences of scale-free networks decay according to a powerlaw distribution, namely $P(k) \sim k^{-γ}$, where $γ$ is a scaling exponent. We derive mean field expressions for $γ$, and test these by numerical simulations. Generally, good agreement is obtained. We also found that some algorithms do not produce scale-free networks (for example some variant Barabasi-Albert and Solé networks).

Quantum computers can in principle solve certain problems exponentially more quickly than their classical counterparts. We have not yet reached the advent of useful quantum computation, but when we do, it will affect nearly all scientific disciplines. In this review, we examine how current quantum algorithms could revolutionize computational biology and bioinformatics. There are potential benefits across the entire field, from the ability to process vast amounts of information and run machine learning algorithms far more efficiently, to algorithms for quantum simulation that are poised to improve computational calculations in drug discovery, to quantum algorithms for optimization that may advance fields from protein structure prediction to network analysis. However, these exciting prospects are susceptible to "hype", and it is also important to recognize the caveats and challenges in this new technology. Our aim is to introduce the promise and limitations of emerging quantum computing technologies in the areas of computational molecular biology and bioinformatics.

Scientific objectivity was not a problem in the early days of molecular biology. However, relativism seems to have invaded some areas of the field, damaging the objectivity of its analyses. This review reports on the status of this issue by investigating a number of cases.

In a recent paper, Wilmes et al. demonstrated a qualitative integration of omics data streams to gain a mechanistic understanding of cyclosporine A toxicity. One of their major conclusions was that cyclosporine A strongly activates the nuclear factor (erythroid-derived 2)-like 2 pathway (Nrf2) in renal proximal tubular epithelial cells exposed in vitro. We pursue here the analysis of those data with a quantitative integration of omics data with a differential equation model of the Nrf2 pathway. That was done in two steps: (i) Modeling the in vitro pharmacokinetics of cyclosporine A (exchange between cells, culture medium and vial walls) with a minimal distribution model. (ii) Modeling the time course of omics markers in response to cyclosporine A exposure at the cell level with a coupled PK-systems biology model. Posterior statistical distributions of the parameter values were obtained by Markov chain Monte Carlo sampling. Data were well simulated, and the known in vitro toxic effect EC50 was well matched by model predictions. The integration of in vitro pharmacokinetics and systems biology modeling gives us a quantitative insight into mechanisms of cyclosporine A oxidative-stress

The molecular machinery of life is largely created via self-organisation of individual molecules into functional assemblies. Minimal coarse-grained models, where a whole macromolecule is represented by a small number of particles, can be of great value in identifying the main driving forces behind self-organisation in cell biology. Such models can incorporate data from both molecular and continuum scales, and their results can be directly compared to experiments. Here we review the state of the art of models for studying the formation and biological function of macromolecular assemblies in cells. We outline the key ingredients of each model and their main findings. We illustrate the contribution of this class of simulations to identifying the physical mechanisms behind life and diseases, and discuss their future developments.

Publication patterns of 79 forest scientists awarded major international forestry prizes during 1990-2010 were compared with the journal classification and ranking promoted as part of the 'Excellence in Research for Australia' (ERA) by the Australian Research Council. The data revealed that these scientists exhibited an elite publication performance during the decade before and two decades following their first major award. An analysis of their 1703 articles in 431 journals revealed substantial differences between the journal choices of these elite scientists and the ERA classification and ranking of journals. Implications from these findings are that additional cross-classifications should be added for many journals, and there should be an adjustment to the ranking of several journals relevant to the ERA Field of Research classified as 0705 Forestry Sciences.