Quantitative Biology

COVID-19 is now a global pandemic, and an effective vaccine may be many months away. Over 100 years ago, Spanish flu fatalities were attenuated when doctors began treating patients with blood plasma donated by recovered (or convalesced) survivors. Passive immunity transfer via administration of convalesced blood product (CBP) appears to represent a readily available and promising avenue for mitigating mortalities, expediting recovery time, and even prophylaxis against the SARS-CoV-2 virus. Here, we review challenges to CBP efficacy, and present a graph theoretical model of transmission dynamics that identifies evolving hubs of COVID-19 cases. Importantly, this model suggests that CBP efficacy may rest on an efficient and distributed global sampling scheme as opposed to CBP pooled from local donors alone.

The usage frequencies for codons belonging to quartets are analized, over the whole exonic region, for 92 biological species. Correlation is put into evidence, between the usage frequencies of synonymous codons with third nucleotide A and C and between the usage frequencies of non synonymous codons, belonging to suitable subsets of the quartets, with the same third nucleotide. A correlation is pointed out between amino acids belonging to subsets of the set encoded by quartets of codons. It is remarked that the computed Shannon entropy for quartets is weakly dependent on the biological species. The observed correlations well fit in the mathematical scheme of the crystal basis model of the genetic code.

Aging is analyzed as the spontaneous loss of adaptivity and increase in fragility that characterizes dynamic systems. Cybernetics defines the general regulatory mechanisms that a system can use to prevent or repair the damage produced by disturbances. According to the law of requisite variety, disturbances can be held in check by maximizing buffering capacity, range of compensatory actions, and knowledge about which action to apply to which disturbance. This suggests a general strategy for rejuvenating the organism by increasing its capabilities of adaptation. Buffering can be optimized by providing sufficient rest together with plenty of nutrients: amino acids, antioxidants, methyl donors, vitamins, minerals, etc. Knowledge and the range of action can be extended by subjecting the organism to an as large as possible variety of challenges. These challenges are ideally brief so as not to deplete resources and produce irreversible damage. However, they should be sufficiently intense and unpredictable to induce an overshoot in the mobilization of resources for damage repair, and to stimulate the organism to build stronger capabilities for tackling future challenges. This allows them to override the trade-offs and limitations that evolution has built into the organism's repair processes in order to conserve potentially scarce resources. Such acute, "hormetic" stressors strengthen the organism in part via the "order from noise" mechanism that destroys dysfunctional structures by subjecting them to strong, random variations. They include heat and cold, physical exertion, exposure, stretching, vibration, fasting, food toxins, micro-organisms, environmental enrichment and psychological challenges.

Evolution consists of distinct stages: cosmological, biological, linguistic. Since biology verges on natural sciences and linguistics, we expect that it shares structures and features from both forms of knowledge. Indeed, in DNA we encounter the biological "atoms", the four nucleotide molecules. At the same time these four nucleotides may be considered as the "letters" of an alphabet. These four "letters", through a genetic code, generate biological "words", "phrases", "sentences" (aminoacids, proteins, cells, living organisms). In this spirit we may consider equally well a DNA strand as a mathematical statement. Inspired by the work of Kurt Gödel, we attach to each DNA strand a Gödel's number, a product of prime numbers raised to appropriate powers. To each DNA chain corresponds a single Gödel's number G , and inversely given a Gödel's number G , we can specify the DNA chain it stands for. Next, considering a single DNA strand composed of N bases, we study the statistical distribution of g , the logarithm of G . Our assumption is that the choice of the m -th term is random and with equal probability for the four possible outcomes. The "experiment", to some extent, appears as throwing N times a four-faces die. Through the moment generating function we obtain the discrete and then the continuum distribution of g . There is an excellent agreement between our formalism and simulated data. At the end we compare our formalism to actual data, to specify the presence of traces of non-random dynamics.

Point mutations can surely be dangerous but what is worst than to lose the reading frame?! Does DNA evolved a strategy to try to limit frameshift mutations?! Here we investigate if DNA sequences effectively evolved a system to minimize frameshift mutations analyzing the transcripts of proteins with high molecular weights.

The theory of cometary panspermia, developed by the late Sir Fred Hoyle and the present author argues that life originated cosmically as a unique event in one of a great multitude of comets or planetary bodies in the Universe. Life on Earth did not originate here but was introduced by impacting comets, and its further evolution was driven by the subsequent acquisition of cosmically derived genes. Explicit predictions of this theory published in 1979-1981, stating how the acquisition of new genes drives evolution, are compared with recent developments in relation to horizontal gene transfer, and the role of retroviruses in evolution. Precisely-stated predictions of the theory of cometary panspermia are shown to have been verified.

Some bacterial and viral DNA sequences have been found to induce low frequency electromagnetic waves in high aqueous dilutions. This phenomenon appears to be triggered by the ambient electromagnetic background of very low frequency. We discuss this phenomenon in the framework of quantum field theory. A scheme able to account for the observations is proposed. The reported phenomenon could allow to develop highly sensitive detection systems for chronic bacterial and viral infections.

The sophisticated tools and techniques employed by Nature for purposeful storage of information stand in stark contrast to the primitive and relatively inefficient means used by man. We describe some impressive features of biological data storage, and speculate on approaches to research and development that could benefit the storage industry in the coming decades.

Modern biology frequently relies on machine learning to provide predictions and improve decision processes. There have been recent calls for more scrutiny on machine learning performance and possible limitations. Here we present a set of community-wide recommendations aiming to help establish standards of supervised machine learning validation in biology. Adopting a structured methods description for machine learning based on data, optimization, model, evaluation (DOME) will aim to help both reviewers and readers to better understand and assess the performance and limitations of a method or outcome. The recommendations are formulated as questions to anyone wishing to pursue implementation of a machine learning algorithm. Answers to these questions can be easily included in the supplementary material of published papers.

What is life. Schrodingers question is discussed here for a specific protein, villin, which builds cells in tissues that detect taste and sound. Villin is represented by a sequence of 827 amino acids bound to a peptide backbone chain. We focus attention on a limited problem, the Darwinian evolution of villin sequences from chickens to humans. This biophysical problem is analyzed using a new physicical method based on thermodynamic domain scaling, a technique that bridges the gap between physical concepts, self-organized criticality, and conventional biostructural practice. It turns out that the evolutionary changes can be explained by Darwinian selection, which is not generally accepted by biologists at the protein level. The presentation is self-contained, and requires no prior experience with proteins at the molecular level.