The Protein Ontology (PRO) provides a formal, logically-based classification of specific protein classes including structured representations of protein isoforms, variants and modified forms. Initially focused on proteins found in human, mouse and Escherichia coli, PRO now includes representations of protein complexes. The PRO Consortium works in concert with the developers of other biomedical ontologies and protein knowledge bases to provide the ability to formally organize and integrate representations of precise protein forms so as to enhance accessibility to results of (...) protein research. PRO (http://pir.georgetown.edu/pro) is part of the Open Biomedical Ontologies (OBO) Foundry. (shrink)

The Protein Ontology (PRO) web resource provides an integrative framework for protein-centric exploration and enables specific and precise annotation of proteins and protein complexes based on PRO. Functionalities include: browsing, searching and retrieving, terms, displaying selected terms in OBO or OWL format, and supporting URIs. In addition, the PRO website offers multiple ways for the user to request, submit, or modify terms and/or annotation. We will demonstrate the use of these tools for protein research and annotation.

The Protein Ontology (PRO; http://proconsortium.org) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates to (...) UniProtKB in that PRO’s organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO’s representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments. (shrink)

The Protein Ontology (PRO; http://purl.obolibrary.org/obo/pr) formally defines and describes taxon-specific and taxon-neutral protein-related entities in three major areas: proteins related by evolution; proteins produced from a given gene; and protein-containing complexes. PRO thus serves as a tool for referencing protein entities at any level of specificity. To enhance this ability, and to facilitate the comparison of such entities described in different resources, we developed a standardized representation of proteoforms using UniProtKB as a sequence reference and PSI-MOD as a (...) post-translational modification reference. We illustrate its use in facilitating an alignment between PRO and Reactome protein entities. We also address issues of scalability, describing our first steps into the use of text mining to identify protein-related entities, the large-scale import of proteoform information from expert curated resources, and our ability to dynamically generate PRO terms. Web views for individual terms are now more informative about closely-related terms, including for example an interactive multiple sequence alignment. Finally, we describe recent improvement in semantic utility, with PRO now represented in OWL and as a SPARQL endpoint. These developments will further support the anticipated growth of PRO and facilitate discoverability of and allow aggregation of data relating to protein entities. (shrink)

Biomedical ontologies are emerging as critical tools in genomic and proteomic research where complex data in disparate resources need to be integrated. A number of ontologies exist that describe the properties that can be attributed to proteins; for example, protein functions are described by Gene Ontology, while human diseases are described by Disease Ontology. There is, however, a gap in the current set of ontologies—one that describes the protein entities themselves and their relationships. We have designed a PRotein Ontology (...) (PRO) to facilitate protein annotation and to guide new experiments. The components of PRO extend from the classification of proteins on the basis of evolutionary relationships to the representation of the multiple protein forms of a gene (products generated by genetic variation, alternative splicing, proteolytic cleavage, and other post-translational modification). PRO will allow the specification of relationships between PRO, GO and other OBO Foundry ontologies. Here we describe the initial development of PRO, illustrated using human proteins from the TGF-beta signaling pathway. (shrink)

The Protein Ontology (PRO) is designed as a formal and principled Open Biomedical Ontologies (OBO) Foundry ontology for proteins. The components of PRO extend from a classification of proteins on the basis of evolutionary relationships at the homeomorphic level to the representation of the multiple protein forms of a gene, including those resulting from alternative splicing, cleavage and/or posttranslational modifications. Focusing specifically on the TGF-beta signaling proteins, we describe the building, curation, usage and dissemination of PRO. PRO (...) provides a framework for the formal representation of protein classes and protein forms in the OBO Foundry. It is designed to enable data retrieval and integration and machine reasoning at the molecular level of proteins, thereby facilitating cross-species comparisons, pathway analysis, disease modeling and the generation of new hypotheses. (shrink)

Representing species-specific proteins and protein complexes in ontologies that are both human and machine-readable facilitates the retrieval, analysis, and interpretation of genome-scale data sets. Although existing protin-centric informatics resources provide the biomedical research community with well-curated compendia of protein sequence and structure, these resources lack formal ontological representations of the relationships among the proteins themselves. The Protein Ontology (PRO) Consortium is filling this informatics resource gap by developing ontological representations and relationships among proteins and their variants and (...) modified forms. Because proteins are often functional only as members of stable protein complexes, the PRO Consortium, in collaboration with existing protein and pathway databases, has launched a new initiative to implement logical and consistent representation of protein complexes. We describe here how the PRO Consortium is meeting the challenge of representing species-specific protein complexes, how protein complex representation in PRO supports annotation of protein complexes and comparative biology, and how PRO is being integrated into existing community bioinformatics resources. The PRO resource is accessible at http://pir.georgetown.edu/pro/. (shrink)

Mitchell & Gronenborn propose that we account for the presence of multiple models of protein structure, each produced in different contexts, through the framework of integrative pluralism. I argue that two interpretations of this framework are available, neither of which captures the relationship between a model and the protein structure it represents or between multiple models of protein structure. Further, it inclines us toward concluding prematurely that models of protein structure are right in their contexts and makes extrapolation of findings (...) from one context to another seem unwarranted. Instead, protein structure determination ought to be understood as modestly monistic. There is one model for every protein in each physicochemical context, and models of the same protein produced in different contexts are compatible with one another. ‘Integrating’ multiple models amounts to extrapolating from one context to another; this is possible because the effect of context on protein folding is relatively weak and predictable. Modest monism better describes the practice of protein structure determination than integrative pluralism and enables greater attention to how context affects protein folding. (shrink)

In the beginning of the 20th century the groundbreaking work of Ramon y Cajal firmly established the neuron doctrine, according to which neurons are the basic structural and functional units of the nervous system. Von Weldeyer coined the term “neuron” in 1891, but the huge leap forward in neuroscience was due to Cajal’s meticulous microscopic observations of brain sections stained with an improved version of Golgi’s la reazione nera (black reaction). The latter improvement of Golgi’s technique made it possible to (...) visualize the arborizations of single neurons that were “colored brownish black even to their finest branchlets, standing out with unsurpassable clarity upon a transparent yellow background. All was sharp as a sketch with Chinese ink”. The high quality of both the visualization of individual nerve cells and the work performed on studying the anatomy of the central nervous system lead Ramon y Cajal to the conclusion that axons output the nervous impulses to the dendrites or the soma of other target neurons. (shrink)

Biochemical kinds such as proteins pose interesting problems for philosophers of science, as they can be studied from the points of view of both biology and chemistry. The relationship between the biological functions of biochemical kinds and the microstructures that they are related to is the key question. This leads us to a more general discussion about ontological reductionism, microstructuralism, and multiple realization at the biology-chemistry interface. On the face of it, biochemical kinds seem to pose a challenge for (...) ontological reductionism and hence motivate a dual theory of chemical and biological kinds, a type of pluralism about natural kinds. But it will be argued that the challenge, which is based on multiple realization, can be addressed. The upshot is that there are reasonable prospects for ontological reductionism about biochemical kinds, which corroborates natural kind monism. (shrink)

It is widely understood that protein functions can be exhaustively described in terms of no single parameter, whether this be amino acid sequence or the three-dimensional structure of the underlying protein molecule. This means that a number of different attributes must be used to create an ontology of protein functions. Certainly much of the required information is already stored in databases such as Swiss-Prot, Protein Data Bank, SCOP and MIPS. But the latter have been developed for different purposes and the (...) separate data-structures which they employ are not conducive to the needed data integration. When we attempt to classify the entities in the domain of proteins, we find ourselves faced with a number of cross-cutting principles of classification. Our question here is: how can we bring together these separate taxonomies in order to describe protein functions? Our proposed answer is: via a careful top-level ontological analysis of the relevant principles of classification, combined with a new framework for the simultaneous manipulation of classifications constructed for different purposes. (shrink)

The short paper introduces the concept of possible branches of double-stranded DNA (later sometimes called palindromes): Certain sequences of nucleotides may be followed, after a short unpaired stretch, by a complementary sequence in reversed order, such that each DNA strand can fold back on itself, and the DNA assumes a cruciform or tree-like structure. This is postulated to interact with regulatory proteins. -/- .

The Protein Ontology provides terms for and supports annotation of species-specific protein complexes in an ontology framework that relates them both to their components and to species-independent families of complexes. Comprehensive curation of experimentally known forms and annotations thereof is expected to expose discrepancies, differences, and gaps in our knowledge. We have annotated the early events of innate immune signaling mediated by Toll-Like Receptor 3 and 4 complexes in human, mouse, and chicken. The resulting ontology and annotation data set has (...) allowed us to identify species-specific gaps in experimental data and possible functional differences between species, and to employ inferred structural and functional relationships to suggest plausible resolutions of these discrepancies and gaps. (shrink)

Protein α-helices provide an ordered biological environment that is conducive to soliton-assisted energy transport. The nonlinear interaction between amide I excitons and phonon deformations induced in the hydrogen-bonded lattice of peptide groups leads to self-trapping of the amide I energy, thereby creating a localized quasiparticle (soliton) that persists at zero temperature. The presence of thermal noise, however, could destabilize the protein soliton and dissipate its energy within a finite lifetime. In this work, we have computationally solved the system of stochastic (...) differential equations that govern the quantum dynamics of protein solitons at physiological temperature, T=310 K, for either a single isolated α-helix spine of hydrogen bonded peptide groups or the full protein α-helix comprised of three parallel α-helix spines. The simulated stochastic dynamics revealed that although the thermal noise is detrimental for the single isolated α-helix spine, the cooperative action of three amide I exciton quanta in the full protein α-helix ensures soliton lifetime of over 30 ps, during which the amide I energy could be transported along the entire extent of an 18-nm-long α-helix. Thus, macromolecular protein complexes, which are built up of protein α-helices could harness soliton-assisted energy transport at physiological temperature. Because the hydrolysis of a single adenosine triphosphate molecule is able to initiate three amide I exciton quanta, it is feasible that multiquantal protein solitons subserve a variety of specialized physiological functions in living systems. (shrink)

Biological order provided by α-helical secondary protein structures is an important resource exploitable by living organisms for increasing the efficiency of energy transport. In particular, self-trapping of amide I energy quanta by the induced phonon deformation of the hydrogen-bonded lattice of peptide groups is capable of generating either pinned or moving solitary waves following the Davydov quasiparticle/soliton model. The effect of applied in-phase Gaussian pulses of amide I energy, however, was found to be strongly dependent on the site of application. (...) Moving solitons were only launched when the amide I energy was applied at one of the α-helix ends, whereas pinned solitons were produced in the α-helix interior. In this paper, we describe a general mechanism that launches moving solitons in the interior of the α-helix through phase-modulated Gaussian pulses of amide I energy. We also compare the predicted soliton velocity based on effective soliton mass and the observed soliton velocity in computer simulations for different parameter values of the isotropy of the exciton-phonon interaction. The presented results demonstrate the capacity for explicit control of soliton velocity in protein α-helices, and further support the plausibility of gradual optimization of quantum dynamics for achieving specialized protein functions through natural selection. (shrink)

The essential biological processes that sustain life are catalyzed by protein nano-engines, which maintain living systems in far-from-equilibrium ordered states. To investigate energetic processes in proteins, we have analyzed the system of generalized Davydov equations that govern the quantum dynamics of multiple amide I exciton quanta propagating along the hydrogen-bonded peptide groups in α-helices. Computational simulations have confirmed the generation of moving Davydov solitons by applied pulses of amide I energy for protein α-helices of varying length. The stability and (...) mobility of these solitons depended on the uniformity of dipole-dipole coupling between amide I oscillators, and the isotropy of the exciton-phonon interaction. Davydov solitons were also able to quantum tunnel through massive barriers, or to quantum interfere at collision sites. The results presented here support a nontrivial role of quantum effects in biological systems that lies beyond the mechanistic support of covalent bonds as binding agents of macromolecular structures. Quantum tunneling and interference of Davydov solitons provide catalytically active macromolecular protein complexes with a physical mechanism allowing highly efficient transport, delivery, and utilization of free energy, besides the evolutionary mandate of biological order that supports the existence of such genuine quantum phenomena, and may indeed demarcate the quantum boundaries of life. (shrink)

Applying mild methods of preparation, part of the ribosomes of rabbit reticulocytes are found in aggregates (later called polyribosomes) of up to six ribosomal units. Upon treatment with RNA-ase, they desintegrate into single ribosomes. The fast-sedimenting aggregates are found to be more active in protein synthesis in terms of incorporation of radioactive amino acids, whereas the single ribosomes are more receptive to stimulation by the artificial messenger RNA poly-U. The findings indicate that the linkage of ribosomes into aggregates is due (...) to the messenger RNA. They support a tape-reading mechanism of protein synthesis whereby growth of the peptide chain is accompanied by shifting the active site of the ribosome from one coding group of nucleotides of the messenger RNA to the next. (shrink)

Abstract: Sickle cell disease (SCD) comprises an inherited blood disorder that is life long and affects many people globally. Despite progress in therapy, SCA is a considerable cause of mortality and morbidity. This study was designed to measure the immunological and inflammatory parameters of patients with sickle cell disease (SCD) and to found if there is any role of it in the pathogenicity of the disease. This study included A total of 32 patients, their ages ranged from 16 to 55 (...) years patients with Sickle cell disease who have been evaluated during vaso occlusive crisis and had been followed up till they attained steady state, and there are 32 normal control subjects matched with patients in age and sex. In general there was elevation in all parameters the study were included in patients than control and particularly in crisis, despite the IgM value which was insignificantly decrease, but the statically significant elevation reported only in CRP, IgG, IgA. (shrink)

Macromolecular protein complexes catalyze essential physiological processes that sustain life. Various interactions between protein subunits could increase the effective mass of certain peptide groups, thereby compartmentalizing protein α-helices. Here, we study the differential effects of applied massive barriers upon the soliton-assisted energy transport within proteins. We demonstrate that excentric barriers, localized onto a single spine in the protein α-helix, reflect or trap three-spine solitons as effectively as concentric barriers with comparable total mass. Furthermore, wider protein solitons, whose energy is (...) lower, require heavier massive barriers for soliton reflection or trapping. Regulation of energy transport, delivery and utilization at protein active sites could thus be achieved through control of the soliton width, or of the effective mass of the protein subunits. (shrink)

that can serve as a foundation for more refined ontologies in the field of proteomics. Standard data sources classify proteins in terms of just one or two specific aspects. Thus SCOP (Structural Classification of Proteins) is described as classifying proteins on the basis of structural features; SWISSPROT annotates proteins on the basis of their structure and of parameters like post-translational modifications. Such data sources are connected to each other by pairwise term-to-term mappings. However, there are obstacles (...) which stand in the way of combining them together to form a robust meta-classification of the needed sort. We discuss some formal ontological principles which should be taken into account within the existing datasources in order to make such a metaclassification possible, taking into account also the Gene Ontology (GO) and its application to the annotation of proteins. (shrink)

Chemical kinds (e.g. gold) are generally treated as having timelessly fixed identities. Biological kinds (e.g. goldfinches) are generally treated as evolved and/or evolving entities. So what kind of kind is a biochemical kind? This paper defends the thesis that biochemical molecules are clustered chemical kinds, some of which–namely, evolutionarily conserved units–are also biological kinds.On this thesis, a number of difficulties that have recently occupied philosophers concerned with proteins and kinds are shown to be resolved or dissolved.

The problem with reductionism in biology is not the reduction, but the implicit attitude of determinism that usually accompanies it. Methodological reductionism is supported by deterministic beliefs, but making such a connection is problematic when it is based on an idea of determinism as fixed predictability. Conflating determinism with predictability gives rise to inaccurate models that overlook the dynamic complexity of our world, as well as ignore our epistemic limitations when we try to model it. Furthermore, the assumption of a (...) strictly deterministic framework is unnecessarily hindering to biology. By removing the dogma of determinism, biological methods, including reductive methods, can be expanded to include stochastic models and probabilistic interpretations. Thus, the dogma of reductionism can be saved once its ties with determinism are severed. In this paper, I analyze two problems that have faced molecular biology for the last 50 years—protein folding and cancer. Both cases demonstrate the long influence of reductionism and determinism on molecular biology, as well as how abandoning determinism has opened the door to more probabilistic and unconstrained reductive methods in biology. (shrink)

The cashew nut is essential for physical and emotional well-being. It is an energetic diet and the best food medication for many illnesses. Nuts protects from malignant growth, coronary illness, circulatory strain, and various degenerative infirmities connected to aging. It can be used for several medicinal purposes. Every part of cashew has some important medicinal properties. Cashew kernel contains proteins, carbohydrates, vitamins, and fats which help gain energy. Cashew nuts are used for many purposes like blood sugar, weight loss, (...) cancer, cold and flu, aging, urinary disorders, digestive disorders, and bone relaxation. In comparing cashew with other nuts, Cashew kernels have good properties, including proteins, carbohydrates, fibers, and minerals, then almond, hazelnut, and walnuts. Cashew kernels contain the highest number of proteins (21%) when compared with Almonds (20.8%), Hazelnuts (15.6%), and Macadamia Nuts (60.9%). Cashew contain large amount of carbohydrate (22%) compared to other nuts like almonds, walnuts, etc. There are some strong benefits of Cashew for health. They boost the immune system, act as an antioxidant, remove gallstones, and beneficial for anemia. They are good sources of healthy fats that are necessary for our body to absorb fat-soluble vitamins. Its bark is known as the antihypertensive and glucose-lowering part. It has beneficial effect on the eyes and skin. This is rich in vitamin C, so it can be used for skin problems like acne, flawless freckles, skin lines and protects from aging. (shrink)

The biomedical literature makes extensive use of the concept of a genetic program. So far, however, the nature of genetic programs has received no satisfactory elucidation from the standpoint of computer science. This unsettling omission has led to doubts about the very existence of genetic programs, on the grounds that gene regulatory networks lack a predetermined schedule of execution, which may seem to contradict the very idea of a program. I show, however, that we can make perfect sense of genetic (...) programs, if only we abandon the preconception that all computers have a von Neumann architecture. Instead, genetic programs instantiate the computational architecture of Post–Newell Production Systems. That is, genetic programs are unordered sets of conditional instructions, instructions that fire independently when their conditions are matched. For illustration I present a paradigm Production System that regulates the functioning of the well-known lac operon of E. coli. On close reflection it turns out that not only genes, but also proteins encode instructions. I propose, therefore, to rename genetic programs to biomolecular programs. Biomolecular and/or genetic programs, and the cellular computers than run them, are to be understood not as von Neumann computers, but as Post–Newell production systems. (shrink)

Modern life sciences research is increasingly relying on artificial intelligence (AI) approaches to model biological systems, primarily centered around the use of machine learning (ML) models. Although ML is undeniably useful for identifying patterns in large, complex data sets, its widespread application in biological sciences represents a significant deviation from traditional methods of scientific inquiry. As such, the interplay between these models and scientific understanding in biology is a topic with important implications for the future of scientific research, yet it (...) is a subject that has received little attention. Here, we draw from an epistemological toolkit to contextualize recent applications of ML in biological sciences under modern philosophical theories of understanding, identifying general principles that can guide the design and application of ML systems to model biological phenomena and advance scientific knowledge. We propose that conceptions of scientific understanding as information compression, qualitative intelligibility, and dependency relation modelling provide a useful framework for interpreting ML-mediated understanding of biological systems. Through a detailed analysis of two key application areas of ML in modern biological research – protein structure prediction and single cell RNA-sequencing – we explore how these features have thus far enabled ML systems to advance scientific understanding of their target phenomena, how they may guide the development of future ML models, and the key obstacles that remain in preventing ML from achieving its potential as a tool for biological discovery. Consideration of the epistemological features of ML applications in biology will improve the prospects of these methods to solve important problems and advance scientific understanding of living systems. (shrink)

Upon separation of the protein from the nucleic acid component of tobacco mosaic virus by phenol, using a fast and gentle procedure, the nucleic acid is infective in assays on tobacco leaves. A series of qualitative and quantitative control experiments demonstrates that the biological activity cannot depend on residual proteins in the preparation, but is a property of isolated nucleic acid which is thus the genetic material of the virus.

A classic analytic approach to biological phenomena seeks to refine definitions until classes are sufficiently homogenous to support prediction and explanation, but this approach founders on cases where a single process produces objects with similar forms but heterogeneous behaviors. I introduce object spaces as a tool to tackle this challenging diversity of biological objects in terms of causal processes with well-defined formal properties. Object spaces have three primary components: (1) a combinatorial biological process such as protein synthesis that generates objects (...) with parts that are modular, independent, and organized according to an invariant syntax; (2) a notion of “distance” that relates the objects according to rules of change over time as found in nature or useful for algorithms; (3) mapping functions defined on the space that map its objects to other spaces or apply an evaluative criterion to measure an important quality, such as parsimony or biochemical function. Once defined, an object space can be used to represent and simulate the dynamics of phenomena on multiple scales; it can also be used as a tool for predicting higher-order properties of the objects, including stitching together series of causal processes. Object spaces are the basis for a strategy of theorizing, discovery, and analysis in biology: as heuristic idealizations of biology, they help us transform inchoate, intractable problems into articulated, well-structured ones. Developing an object space is a research strategy with a long, successful history under many other names, and it offers a unifying but not overreaching approach to biological theory. (shrink)

I consider some hitherto unexplored examples of teleological language in the sciences. In explicating these examples, I aim to show (a) that such language is not the sole preserve of the biological sciences, and (b) that not all such talk is reducible to the ascription of functions. In chemistry and biochemistry, scientists explaining molecular rearrangements and protein folding talk informally of molecules rearranging “in order to” maximize stability. Evolutionary biologists, meanwhile, often speak of traits evolving “in order to” optimize some (...) fitness-relevant variable. I argue that in all three contexts such locutions are best interpreted as shorthands for more detailed explanations which, were we to spell them out in full, would show that the relevant process would robustly converge towards the same end-point despite variation in initial conditions. This suggests that, in biology, such talk presupposes a substantial form of adaptationism. The upshot is that such shorthands may be more applicable in the physical sciences than the biological. (shrink)

Biomolecules and particularly proteins and DNA exhibit some mysterious features that cannot find satisfactory explanation by quantum mechanical modes of atoms. One of them, known as a Levinthal’s paradox, is the ability to preserve their complex three-dimensional structure in appropriate environments. Another one is that they possess some unknown energy mechanism. The Basic Structures of Matter Supergravitation Unified Theory (BSM-SG) allows uncovering the real physical structures of the elementary particles and their spatial arrangement in atomic nuclei. The resulting physical (...) models of the atoms are characterized by the same interaction energies as the quantum mechanical models, while the structure of the elementary particles influence their spatial arrangement in the nuclei. The resulting atomic models with fully identifiable parameters and angular positions of the quantum orbits permit studying the physical conditions behind the structural and bonding restrictions of the atoms connected in molecules. A new method for a theoretical analysis of biomolecules is proposed. The analysis of a DNA molecule leads to formulation of hypotheses about the energy storage mechanism in DNA and its role in the cell cycle synchronization. This permits shedding a light on the DNA feature known as a C-value paradox. The analysis of a tRNA molecule leads to formulation of a hypothesis about a binary decoding mechanism behind the 20 flavors of the complex aminoacyle-tRNA synthetases - tRNA, known as a paradox. (shrink)

Because factory-farmed meat production inflicts gratuitous suffering upon animals and wreaks havoc on the environment, there are morally compelling reasons to become vegetarian. Yet industrial plant agriculture causes the death of many field animals, and this leads some to question whether consumers ought to get some of their protein from certain kinds of non factory-farmed meat. Donald Bruckner, for instance, boldly argues that the harm principle implies an obligation to collect and consume roadkill and that strict vegetarianism is thus immoral. (...) But this argument works only if the following claims are true: all humans have access to roadkill, roadkill would go to waste if those who happen upon it don’t themselves consume it, it’s impossible to harvest vegetables without killing animals, the animals who are killed in plant production are all-things-considered harmed by crop farming, and the best arguments for vegetarianism all endorse the harm principle. As I will argue in this paper, each claim is deeply problematic. Consequently, in most cases, humans ought to strictly eat plants and save the roadkill for cats. (shrink)

While Darwin is commonly supposed to have demonstrated the inapplicability of the Aristotelian ontology of species to biological science, recent developments, especially in the wake of the Human Genome Project, have given rise to a new golden age of classification in which ontological ideas -- as for example in the Gene Ontology, the Cell Ontology, the Protein Ontology, and so forth -- are once again playing an important role. In regard to species, on the other hand, matters are more complex. (...) We provide a brief overview of recent proposals concerning the ontology of species, dealing with species as sets, classes and as collections, the views of Ernst Meyr, and mereological views. (shrink)

It has become customary to conceptualize the living cell as an intricate piece of machinery, different to a man-made machine only in terms of its superior complexity. This familiar understanding grounds the conviction that a cell's organization can be explained reductionistically, as well as the idea that its molecular pathways can be construed as deterministic circuits. The machine conception of the cell owes a great deal of its success to the methods traditionally used in molecular biology. However, the recent introduction (...) of novel experimental techniques capable of tracking individual molecules within cells in real time is leading to the rapid accumulation of data that are inconsistent with an engineering view of the cell. This paper examines four major domains of current research in which the challenges to the machine conception of the cell are particularly pronounced: cellular architecture, protein complexes, intracellular transport, and cellular behaviour. It argues that a new theoretical understanding of the cell is emerging from the study of these phenomena which emphasizes the dynamic, self-organizing nature of its constitution, the fluidity and plasticity of its components, and the stochasticity and non-linearity of its underlying processes. (shrink)

Background: A bean is the seed of one of several genera of the flowering plant family Fabaceae, which are used as vegetables for human or animal food. They can be cooked in many different ways, including boiling, frying, and baking, and are used in many traditional dishes throughout the world. Beans are one of the longest-cultivated plants. Broad beans, also called fava beans, in their wild state the size of a small fingernail, were gathered in Afghanistan and the Himalayan foothills. (...) In a form improved from naturally occurring types, Beans were an important source of protein throughout old and new world history, and still are today. Objectives: The main goal of this expert system is to get the appropriate diagnosis of disease and the correct treatment. Methods: In this paper, the design of the proposed Expert System was produced to help farmers and those interested in agriculture in diagnosing many of the Bean diseases such as Fusarium wilt, Charcoal rot or ashy stem blight, Bacterial leaf spot and blight, Mung bean yellow mosaic virus, Cercospora leaf spot. The proposed expert system presents an overview of Bean diseases are given, the cause of diseases outlined and the treatment of disease whenever possible is given out. CLIPS Expert System language was used for designing and implementing the proposed expert system. Results: The proposed Bean diseases diagnosis expert system was evaluated by Agricultural experts and some friends interested in agriculture and they were satisfied with its performance. Conclusions: The proposed expert system is very useful for Farmers and those interested in agriculture. (shrink)

Following Kripke and Putnam, the received view of chemical kinds has been a microstructuralist one. To be a microstructuralist about chemical kinds is to think that membership in said kinds is conferred by microstructural properties. Recently, the received microstructuralist view has been elaborated and defended, but it has also been attacked on the basis of complexities, both chemical and ontological. Here, I look at which complexities really challenge the microstructuralist view; at how the view itself might be made more complicated (...) in order to accommodate such challenges; and finally, at what this increasingly complicated picture implies for our standard assessment of chemical kindhood—primarily, for the widespread assumption that chemical kinds in general are more neat and tidy than those messy biological ones. _1_ The Received View _2_ A Taxonomy of Chemical Kinds _3_ Atomic Number _4_ H2O, H3O+, OH−, and More _5_ Complicating the Microstructuralist Picture _6_ Concrete and Other Mixtures _7_ Macromolecules, Especially Proteins _8_ Abandoning Sameness of Elemental Composition _9_ Not So Different after All. (shrink)

The mathematical universe hypothesis is a theory that the physical universe is not merely described by mathematics, but is mathematics, specifically a mathematical structure. Our research provides evidence that the mathematical structure of the universe is biological in nature and all systems, processes, and objects within the universe function in harmony with biological patterns. Living organisms are the result of the universe’s biological pattern and are embedded within their physiology the patterns of this biological universe. Therefore physiological patterns in living (...) organisms can be used as models to structurally map analogies from the biological domain to any target domain to reveal and understand the biological nature of the target domain. Our paper explores various analogies, structurally mapping a red blood cell to a cup; proteins produced from ribosomes to music produced from instruments; a beating heart to the melting and freezing of Antartica; cells, tissue, organs and blood, to people, organizations, industries, and money, and; bio-economic concepts in cellular society to socioeconomic concepts in human society. It also discusses how phenomena in cellular mitosis can help explain phenomena in the universe, such as black holes, dark matter, dark energy, and the structure of the universe. Building upon the concept of perennial wisdom, our research has provided evidence that the ideas of a biological universe were expressed across many past cultures and historical periods. The implications of this theory are vast, encompassing fields such as physics, science, philosophy, religion, law, economics, politics, and engineering, thus serving as a unifying theory for all knowledge. Our theory is supported by meta-analysis of scientific, historic, and religious literature, observations and first principles logic. (shrink)

Forty years’ experience as a bacterial geneticist has taught me that bacteria possess many cognitive, computational and evolutionary capabilities unimaginable in the first six decades of the twentieth century. Analysis of cellular processes such as metabolism, regulation of protein synthesis, and DNA repair established that bacteria continually monitor their external and internal environments and compute functional outputs based on information provided by their sensory apparatus. Studies of genetic recombination, lysogeny, antibiotic resistance and my own work on transposable elements revealed multiple (...) widespread bacterial systems for mobilizing and engineering DNA molecules. Examination of colony development and organization led me to appreciate how extensive multicellular collaboration is among the majority of bacterial species. Contemporary research in many laboratories on cell–cell signaling, symbiosis and pathogenesis show that bacteria utilise sophisticated mechanisms for intercellular communication and even have the ability to commandeer the basic cell biology of ‘higher’ plants and animals to meet their own needs. This remarkable series of observations requires us to revise basic ideas about biological information processing and recognise that even the smallest cells are sentient beings. Previous article in issue. (shrink)

In a now classic paper published in 1991, Alberch introduced the concept of genotype–phenotype (G!P) mapping to provide a framework for a more sophisticated discussion of the integration between genetics and developmental biology that was then available. The advent of evo-devo first and of the genomic era later would seem to have superseded talk of transitions in phenotypic space and the like, central to Alberch’s approach. On the contrary, this paper shows that recent empirical and theoretical advances have only sharpened (...) the need for a different conceptual treat- ment of how phenotypes are produced. Old-fashioned metaphors like genetic blueprint and genetic programme are not only woefully inadequate but positively misleading about the nature of G!P, and are being replaced by an algorithmic approach emerging from the study of a variety of actual G!P maps. These include RNA folding, protein function and the study of evolvable soft- ware. Some generalities are emerging from these disparate fields of analysis, and I suggest that the concept of ‘developmental encoding’ (as opposed to the classical one of genetic encoding) provides a promising computational–theoretical underpinning to coherently integrate ideas on evolvability, modularity and robustness and foster a fruitful framing of the G!P mapping problem. (shrink)

In the future, human destiny may depend on our ethics. In particular, biotechnology and expansion in space can transform life, raising profound questions. Guidance may be found in Life-centered ethics, as biotic ethics that value the basic patterns of organic gene/protein life, and as panbiotic ethics that always seek to expand life. These life-centered principles can be based on scientific insights into the unique place of life in nature, and the biological unity of all life. Belonging to life then implies (...) a human purpose: to safeguard and propagate life. Expansion in space will advance this purpose but will also raise basic questions. Should we expand all life or only intelligent life? Should we aim to create populations of trillions? Should we seed other solar systems? How far can we change but still preserve the human species, and life itself? The future of all life may be in our hands, and it can depend on our guiding ethics whether life will fulfil its full potentials. Given such profound powers, life-centered ethics can best secure future generations. Our descendants may then understand nature more deeply, and seek to extend life indefinitely. In that future, our human existence can find a cosmic purpose. (shrink)

I present a reconstruction of F.H.C. Crick's two 1957 hypotheses "Sequence Hypothesis" and "Central Dogma" in terms of a contemporary philosophical theory of causation. Analyzing in particular the experimental evidence that Crick cited, I argue that these hypotheses can be understood as claims about the actual difference-making cause in protein synthesis. As these hypotheses are only true if restricted to certain nucleic acids in certain organisms, I then examine the concept of causal specificity and its potential to counter claims about (...) causal parity of DNA and other cellular components. I first show that causal specificity is a special kind of invariance under interventions, namely invariance of generalizations that range over finite sets of discrete variables. Then, I show that this notion allows the articulation of a middle ground in the debate over causal parity. (shrink)

We introduce a new type of pluralism about biological function that, in contrast to existing, demonstrates a practical integration among the term’s different meanings. In particular, we show how to generalize Sandra Mitchell’s notion of integrative pluralism to circumstances where multiple epistemic tools of the same type are jointly necessary to solve scientific problems. We argue that the multiple definitions of biological function operate jointly in this way based on how biologists explain the evolution of protein function. To clarify how (...) our account relates to existing views, we introduce a general typology for monist and pluralist accounts along with standardized criteria for judging which is best supported by evidence. (shrink)

Different chemical species are often cited as paradigm examples of structurally delimited natural kinds. While classificatory monism may thus seem plausible for simple molecules, it looks less attractive for complex biological macromolecules. I focus on the case of proteins that are most plausibly individuated by their functions. Is there a single, objective count of proteins? I argue that the vagaries of function individuation infect protein classification. We should be pluralists about macromolecular classification.

In the wake of the advent of genome editing technology CRISPR-Cas9 (clustered regularly interspaced palindromic repeat (CRISPR)-associated protein 9), there has been a global debate around the implications of manipulating the human genome. While CRISPR-based germline gene editing is new, the debate about the ethics of gene editing is not – for several decades now, scholars have debated the ethics of making heritable changes to the human genome. The arguments that have been raised both for and against the use of (...) genetic technologies in human reproduction reiterate much of the arguments made in the pre-CRISPR debate. As such, it is instructive for South Africa to reflect on these arguments now, in considering our position on the regulation of the use of this novel biotechnology. There are two dominant schools of thought in this area, bioliberalism and bioconservatism. Bioconservatives raise concerns about the risks of genetic manipulation, and argue that it ought to be limited or prohibited to avert these risks to human health and human nature. Bioliberal scholars are more open to the prospect of genetic manipulation, because of its potential utility. In this article, I conclude that in liberal democracies such as our own, bioliberal arguments ought to be seriously considered when formulating policy on human genome editing because of the extent to which they resonate with our Constitutional values and human rights. I further suggest that there is a need for an enquiry into the relevance of African perspectives on the ethical questions that arise concerning germline genome editing. (shrink)

Terms loaded with informational connotations are often employed to refer to genes and their dynamics. Indeed, genes are usually perceived by biologists as basically ‘the carriers of hereditary information.’ Nevertheless, a number of researchers consider such talk as inadequate and ‘just metaphorical,’ thus expressing a skepticism about the use of the term ‘information’ and its derivatives in biology as a natural science. First, because the meaning of that term in biology is not as precise as it is, for instance, in (...) the mathematical theory of communication. Second, because it seems to refer to a purported semantic property of genes without theoretically clarifying if any genuinely intrinsic semantics is involved. Biosemiotics, a field that attempts to analyze biological systems as semiotic systems, makes it possible to advance in the understanding of the concept of information in biology. From the perspective of Peircean biosemiotics, we develop here an account of genes as signs, including a detailed analysis of two fundamental processes in the genetic information system (transcription and protein synthesis) that have not been made so far in this field of research. Furthermore, we propose here an account of information based on Peircean semiotics and apply it to our analysis of transcription and protein synthesis. (shrink)

This paper examines the adequacy of causal graph theory as a tool for modeling biological phenomena and formalizing biological explanations. I point out that the causal graph approach reaches it limits when it comes to modeling biological phenomena that involve complex spatial and structural relations. Using a case study from molecular biology, DNA-binding and -recognition of proteins, I argue that causal graph models fail to adequately represent and explain causal phenomena in this field. The inadequacy of these models is (...) due to their failure to include relevant spatial and structural information in a way that does not render the model non-explanatory, unmanageable, or inconsistent with basic assumptions of causal graph theory. (shrink)

The fields of quantum biology and physics are now starting to unite to solve the mysteries associated with the field of evolutionary biology. One such question is the origination and propagation of consciousness which has always been ambiguous and in order to understand this concept, many theories have been proposed by several philosophers and scientists. This review paper agrees with the idea, that evolution is not a random process but hypothesizes, that its succession was managed by the expanding level of (...) consciousness due to cell division and cell differentiation. Several theories propose that the cytoskeleton and its proteins are promoters for consciousness in the brain, which propagates by means of super-conductance. A better correlation of cytoskeletal evolution and consciousness could help solve the enigma of the origination, propagation and existence of consciousness. This review is a compilation of theories, evidences and scientific studies which intends to bring an association between propagation of consciousness and the evolution of the cytoskeleton and its proteins. (shrink)

The current COVID-19 pandemic and the previous SARS/MERS outbreaks of 2003 and 2012 have resulted in a series of major global public health crises. We argue that in the interest of developing effective and safe vaccines and drugs and to better understand coronaviruses and associated disease mechenisms it is necessary to integrate the large and exponentially growing body of heterogeneous coronavirus data. Ontologies play an important role in standard-based knowledge and data representation, integration, sharing, and analysis. Accordingly, we initiated the (...) development of the community-based Coronavirus Infectious Disease Ontology in early 2020. -/- As an Open Biomedical Ontology (OBO) library ontology, CIDO is open source and interoperable with other existing OBO ontologies. CIDO is aligned with the Basic Formal Ontology and Viral Infectious Disease Ontology. CIDO has imported terms from over 30 OBO ontologies. For example, CIDO imports all SARS-CoV-2 protein terms from the Protein Ontology, COVID-19-related phenotype terms from the Human Phenotype Ontology, and over 100 COVID-19 terms for vaccines (both authorized and in clinical trial) from the Vaccine Ontology. CIDO systematically represents variants of SARS-CoV-2 viruses and over 300 amino acid substitutions therein, along with over 300 diagnostic kits and methods. CIDO also describes hundreds of host-coronavirus protein-protein interactions (PPIs) and the drugs that target proteins in these PPIs. CIDO has been used to model COVID-19 related phenomena in areas such as epidemiology. The scope of CIDO was evaluated by visual analysis supported by a summarization network method. CIDO has been used in various applications such as term standardization, inference, natural language processing (NLP) and clinical data integration. We have applied the amino acid variant knowledge present in CIDO to analyze differences between SARS-CoV-2 Delta and Omicron variants. CIDO's integrative host-coronavirus PPIs and drug-target knowledge has also been used to support drug repurposing for COVID-19 treatment. -/- CIDO represents entities and relations in the domain of coronavirus diseases with a special focus on COVID-19. It supports shared knowledge representation, data and metadata standardization and integration, and has been used in a range of applications. (shrink)

Synthetic biology (SynBio) covers two main areas: application engineering, exemplified by metabolic engi- neering, and the design of life from artificial building blocks. As the general public is often reluctant to embrace synthetic approaches, preferring nature to artifice, its immediate future will depend very much on the public’s reaction to the unmet needs created by the pervasive demands of sustainability. On the other hand, this reluctance should not have a negative impact on research that will now take into account the (...) existence of the multiple transitions that cells face over time. The ages of life—birth, development, maturation, senescence and death—reflect specific key transitions and have, until now, rarely been taken into account in SynBio designs. This results in a mismatch between novelty and the very long evolutionary time that led to the existing chassis [remember that this is the common term used to describe the cellular framework as seen by synthetic biologists (de Lorenzo & Danchin, 2008)]. It also implies that, in general, transitions between growth stages will be taken into account with the appro- priate embodiment of highly specific processes. This is particularly important when adapting new models to their host, whether natural or artificial. Adaptation fol- lows two stages, short-term accommodation of new entities and long-term assimilation into the cell as a whole. This requires discrimination between classes of entities. We suggest that proteins playing the essential role of Maxwell’ demons, here named Maxwell’s dis- criminators (MxDs) to refer to their original function, will permit the assimilation and accommodation of artificial constructs. As a consequence, we can foresee that class discrimination, beyond mere recognition, will be implemented in SynBio 2.0, leading to an authentic par- adigm shift (Kuhn, 1996), based on conceptions that embody information as a genuine currency of reality. (shrink)

In domains as disparate as playing Go and predicting the structure of proteins, artificial intelligence (AI) technologies have begun to perform at levels beyond which any humans can achieve. Does this fact represent something lamentable? Does superhuman AI performance somehow undermine the value of human achievements in these areas? Go grandmaster Lee Sedol suggested as much when he announced his retirement from professional Go, blaming the advances of Go-playing programs like AlphaGo for sapping his will to play the game (...) at a high level. In this paper, I attempt to make sense of Sedol’s lament. I consider a number of ways that the existence of superhuman-performing AI technologies could undermine the value of human achievements. I argue there is very little in the nature of the technology itself that warrants such despair. (Compare: does the existence of a fighter jet undermine the value of being the fastest human sprinter?) But I also argue there are several more localized domains where these technologies threaten to displace human beings from being able to achieve valuable things at all. This is a particular worry for those in unequal societies, I argue, given the difficulty of many achievements and the corresponding amount of resources needed to achieve great things. (shrink)

The Plant Ontology (PO; http://www.plantontology.org/) is a publicly-available, collaborative effort to develop and maintain a controlled, structured vocabulary (“ontology”) of terms to describe plant anatomy, morphology and the stages of plant development. The goals of the PO are to link (annotate) gene expression and phenotype data to plant structures and stages of plant development, using the data model adopted by the Gene Ontology. From its original design covering only rice, maize and Arabidopsis, the scope of the PO has been expanded (...) to include all green plants. The PO was the first multi-species anatomy ontology developed for the annotation of genes and phenotypes. Also, to our knowledge, it was one of the first biological ontologies that provides translations (via synonyms) in non-English languages such as Japanese and Spanish. There are about 2.2 million annotations linking PO terms to over 110,000 unique data objects representing genes or gene models, proteins, RNAs, germplasm and Quantitative Traits Loci (QTLs) from 22 plant species. In this paper, we focus on the plant anatomical entity branch of the PO, describing the organizing principles, resources available to users, and examples of how the PO is integrated into other plant genomics databases and web portals. We also provide two examples of comparative analyses, demonstrating how the ontology structure and PO-annotated data can be used to discover the patterns of expression of the LEAFY (LFY) and terpene synthase (TPS) gene homologs. (shrink)

Assembly of minimal genomes revealed many genes encoding unknown functions. Three overlooked functional categories account for some of them. Cells are prone to make errors and age. As a first key function, discrimination between proper and changed entities is indispensable. Discrimination requires management of information, an authentic, yet abstract, cur- rency of reality. For example proteins age, sometimes very fast. The cell must identify, then get rid of old proteins without destroying young ones. Implementing discrimination in cells leads (...) to the second set of functions, usually ignored. Being abstract, information must nevertheless be embodied into material entities, with unavoidable idiosyncratic properties. This brings about novel unmet needs. Hence, the buildup of cells elicits specific but awkward material implementations, ‘kludges’ that become essential under particular settings, while difficult to identify. Finally, a third functional category char- acterizes the need for growth, with metabolic implementations allowing the cell to put together the growth of its cytoplasm, membranes, and genome, spanning different spatial dimensions. Solving this metabolic quandary, critical for engineering novel synthetic biology chassis, uncovered an unexpected role for CTP synthetase as the coordinator of nonhomothetic growth. Because a significant number of SynBio constructs aim at creating cell factories we expect that they will be attacked by viruses (it is not by chance that the function of the CRISPR system was identified in industrial settings). Substantiating the role of CTP, natural selection has dealt with this hurdle via synthesis of the antimetabolite 30-deoxy-30,40-didehydro- CTP, recruited for antiviral immunity in all domains of life. (shrink)