arXiv Quantitative Biology @arxiv_bio@qoto.org

Human addiction, as a learned behaviour, has and is constantly being treated psychologically, with specific and timely interventions from Neuroscience. We endorse that human addiction can receive further boost as regards treatment, when we firmly understand how it works from a quantum scale. This is majorly because the dopaminergic pathway (DP) that is well elaborated in the brain of every addict is connected to the memory pathway. This further implies that the recall process in the brain of the addict, as regards his/her addiction is fully functional in line with the pleasure that arises from the element of his/her addiction. This dopamine-led pathway shows itself as prominent in what pertains to addiction, this is because of the role it plays in reward. As a neurotransmitter, dopamine flickers when reward is in the offing. It should be noted that a full understanding of the dimensions of addiction in the human person has not be attained to, therefore, we seek to add to this ongoing research, by considering excerpts arising from Quantum Field Theory. We are introducing excerpts from QFT, because DP, is an attendant element in the process of reward and motivation. In clear terms, we are alluding that it all begins with the memory.

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN - a multi-view, weakly-supervised deep clustering method - which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer's disease and brain endophenotypes associated with hypertension, from MRI and SNP data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-driven neuroimaging phenotypes.

Learning from 3D biological macromolecules with artificial intelligence technologies has been an emerging area. Computational protein design, known as the inverse of protein structure prediction, aims to generate protein sequences that will fold into the defined structure. Analogous to protein design, RNA design is also an important topic in synthetic biology, which aims to generate RNA sequences by given structures. However, existing RNA design methods mainly focus on the secondary structure, ignoring the informative tertiary structure, which is commonly used in protein design. To explore the complex coupling between RNA sequence and 3D structure, we introduce an RNA tertiary structure modeling method to efficiently capture useful information from the 3D structure of RNA. For a fair comparison, we collect abundant RNA data and split the data according to tertiary structures. With the standard dataset, we conduct a benchmark by employing structure-based protein design approaches with our RNA tertiary structure modeling method. We believe our work will stimulate the future development of tertiary structure-based RNA design and bridge the gap between the RNA 3D structures and sequences.

Protein-ligand binding prediction is a fundamental problem in AI-driven drug discovery. Prior work focused on supervised learning methods using a large set of binding affinity data for small molecules, but it is hard to apply the same strategy to other drug classes like antibodies as labelled data is limited. In this paper, we explore unsupervised approaches and reformulate binding energy prediction as a generative modeling task. Specifically, we train an energy-based model on a set of unlabelled protein-ligand complexes using SE(3) denoising score matching and interpret its log-likelihood as binding affinity. Our key contribution is a new equivariant rotation prediction network called Neural Euler's Rotation Equations (NERE) for SE(3) score matching. It predicts a rotation by modeling the force and torque between protein and ligand atoms, where the force is defined as the gradient of an energy function with respect to atom coordinates. We evaluate NERE on protein-ligand and antibody-antigen binding affinity prediction benchmarks. Our model outperforms all unsupervised baselines (physics-based and statistical potentials) and matches supervised learning methods in the antibody case.

The use of biodegradable polymers simplifies the development of therapeutic devices with regards to transient implants and three-dimensional platform suitable for tissue engineering. Further advances have also occurred in the controlled released mechanism of bioactive compounds encapsulated in biodegradable polymers. This application requires the understanding of the physicochemical properties of the polymeric materials and their inherent impact on the delivery of encapsulated bioactive. Hence, the objective of this study was to evaluate the effect of surfactant and sonication time on the bio-accessibility of lycopene encapsulated polymeric nanoparticles. The emulsion evaporation method was used to encapsulate lycopene in poly-lactic co-glycolic acid (PLGA) with surfactant concentration, sonication time and polymer concentration as independent variables. Physicochemical and morphological characteristics were measured with a zetasizer and SEM, while the encapsulation efficiency and controlled release kinetics with spectrophotometric, and the dialysis method was used to estimate bioaccessibility. The results have shown sonication time to have significantly (p < 0.05) influenced the encapsulation efficiency. Hence, the sonication time of 4 min yield an encapsulation efficiency of 78% and increased to 97% with increase sonication time (6 min). Increased sonication time had a decreasing effect on the hydrodynamic diameter and stability of the encapsulated nanoparticles. The slow release of lycopene was observed during the first 12 days, followed by a burst release of about 44% on the 13th day in-vitro. The study will have significant impact on the manufacturing of functional food with encapsulated ingredients and provide an understanding of their inherent control release mechanism in the GIT.

Topological data analysis (TDA) is an emerging field in mathematics and data science. Its central technique, persistent homology, has had tremendous success in many science and engineering disciplines. However, persistent homology has limitations, including its incapability of describing the homotopic shape evolution of data during filtration. Persistent topological Laplacians (PTLs), such as persistent Laplacian and persistent sheaf Laplacian, were proposed to overcome the drawback of persistent homology. In this work, we examine the modeling and analysis power of PTLs in the study of the protein structures of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor binding domain (RBD) and its variants, i.e., Alpha, Beta, Gamma, BA.1, and BA.2. First, we employ PTLs to study how the RBD mutation-induced structural changes of RBD-angiotensin-converting enzyme 2 (ACE2) binding complexes are captured in the changes of spectra of the PTLs among SARS-CoV-2 variants. Additionally, we use PTLs to analyze the binding of RBD and ACE2-induced structural changes of various SARS-CoV-2 variants. Finally, we explore the impacts of computationally generated RBD structures on PTL-based machine learning, including deep learning, and predictions of deep mutational scanning datasets for the SARS-CoV-2 Omicron BA.2 variant. Our results indicate that PTLs have advantages over persistent homology in analyzing protein structural changes and provide a powerful new TDA tool for data science.

Contemporary approaches to instance segmentation in cell science use 2D or 3D convolutional networks depending on the experiment and data structures. However, limitations in microscopy systems or efforts to prevent phototoxicity commonly require recording sub-optimally sampled data regimes that greatly reduces the utility of such 3D data, especially in crowded environments with significant axial overlap between objects. In such regimes, 2D segmentations are both more reliable for cell morphology and easier to annotate. In this work, we propose the Projection Enhancement Network (PEN), a novel convolutional module which processes the sub-sampled 3D data and produces a 2D RGB semantic compression, and is trained in conjunction with an instance segmentation network of choice to produce 2D segmentations. Our approach combines augmentation to increase cell density using a low-density cell image dataset to train PEN, and curated datasets to evaluate PEN. We show that with PEN, the learned semantic representation in CellPose encodes depth and greatly improves segmentation performance in comparison to maximum intensity projection images as input, but does not similarly aid segmentation in region-based networks like Mask-RCNN. Finally, we dissect the segmentation strength against cell density of PEN with CellPose on disseminated cells from side-by-side spheroids. We present PEN as a data-driven solution to form compressed representations of 3D data that improve 2D segmentations from instance segmentation networks.

Music is frequently used to establish atmosphere and to enhance/alter emotion in dramas and films. During music listening, visual imagery is a common mechanism underlying emotion induction. The present functional magnetic resonance imaging (fMRI) study examined the neural substrates of the emotional processing of music and imagined scene. A factorial design was used with factors emotion valence (positive; negative) and music (withoutMUSIC: script-driven imagery of emotional scenes; withMUSIC: script-driven imagery of emotional scenes and simultaneously listening to affectively congruent music). The baseline condition was imagery of neutral scenes in the absence of music. Eleven females and five males participated in this fMRI study. The contrasts of positive and negative withoutMUSIC conditions minus the baseline (imagery of neutral scenes) showed no significant activation. When comparing the withMUSIC to withoutMUSIC conditions, activity in a number of emotion-related regions was observed, including the temporal pole (TP), amygdala, hippocampus, hypothalamus, anterior ventral tegmental area (VTA), locus coeruleus, and anterior cerebellum. We hypothesized that the TP may integrate music and the imagined scene to extract socioemotional significance, initiating the subcortical structures to generate subjective feelings and bodily responses. For the withMUSIC conditions, negative emotions were associated with enhanced activation in the posterior VTA compared to positive emotions. Our findings replicated and extended previous research which suggests that different subregions of the VTA are sensitive to rewarding and aversive stimuli. Taken together, this study suggests that emotional music embedded in an imagined scenario is a salient social signal that prompts preparation of approach/avoidance behaviours and emotional responses in listeners.

The major intrinsic protein (MIP) of the lens fiber cell membrane plays a role in lens biogenesis and maintenance. Its polypeptide chains span the membrane six times, and the protein is naturally divided into two halves. We use modern sequence analysis to identify differences between halves for humans (common to animals) and chickens (common to birds).

Artificial intelligence has made significant advances in recent years and this has had an impact on the field of neuroscience. As a result, different architectures have been implemented to extract features from EEG signals in real time. However, the use of such architectures requires a lot of computing power. As a result, EEG devices typically act only as transmitters of EEG data, with the actual data processing taking place in a third-party device. That's expensive and not compact. In this paper, we present a shield that allows a single-board computer, the Jetson Nano from Nvidia, to be converted into a brain-computer interface and, most importantly, the Jetson Nano's capabilities allow machine learning tools to be used directly on the data collection device. Here we present the test results of the developed device. https://github.com/HackerBCI/EEG-with-JetsonNano

Humans perceive discrete events such as "restaurant visits" and "train rides" in their continuous experience. One important prerequisite for studying human event perception is the ability of researchers to quantify when one event ends and another begins. Typically, this information is derived by aggregating behavioral annotations from several observers. Here we present an alternative computational approach where event boundaries are derived using a large language model, GPT-3, instead of using human annotations. We demonstrate that GPT-3 can segment continuous narrative text into events. GPT-3-annotated events are significantly correlated with human event annotations. Furthermore, these GPT-derived annotations achieve a good approximation of the "consensus" solution (obtained by averaging across human annotations); the boundaries identified by GPT-3 are closer to the consensus, on average, than boundaries identified by individual human annotators. This finding suggests that GPT-3 provides a feasible solution for automated event annotations, and it demonstrates a further parallel between human cognition and prediction in large language models. In the future, GPT-3 may thereby help to elucidate the principles underlying human event perception.

For reaction networks arising in systems biology, the capacity for two or more steady states, that is, multistationarity, is an important property that underlies biochemical switches. Another property receiving much attention recently is absolute concentration robustness (ACR), which means that some species concentration is the same at all positive steady states. In this work, we investigate the prevalence of each property while paying close attention to when the properties occur together. Specifically, we consider a stochastic block framework for generating random networks, and prove edge-probability thresholds at which - with high probability - multistationarity appears and ACR becomes rare. We also show that the small window in which both properties occur only appears in networks with many species. Taken together, our results confirm that, in random reversible networks, ACR and multistationarity together, or even ACR on its own, is highly atypical. Our proofs rely on two prior results, one pertaining to the prevalence of networks with deficiency zero, and the other "lifting" multistationarity from small networks to larger ones.

Plant phenotyping is typically a time-consuming and expensive endeavor, requiring large groups of researchers to meticulously measure biologically relevant plant traits, and is the main bottleneck in understanding plant adaptation and the genetic architecture underlying complex traits at population scale. In this work, we address these challenges by leveraging few-shot learning with convolutional neural networks (CNNs) to segment the leaf body and visible venation of 2,906 P. trichocarpa leaf images obtained in the field. In contrast to previous methods, our approach (i) does not require experimental or image pre-processing, (ii) uses the raw RGB images at full resolution, and (iii) requires very few samples for training (e.g., just eight images for vein segmentation). Traits relating to leaf morphology and vein topology are extracted from the resulting segmentations using traditional open-source image-processing tools, validated using real-world physical measurements, and used to conduct a genome-wide association study to identify genes controlling the traits. In this way, the current work is designed to provide the plant phenotyping community with (i) methods for fast and accurate image-based feature extraction that require minimal training data, and (ii) a new population-scale data set, including 68 different leaf phenotypes, for domain scientists and machine learning researchers. All of the few-shot learning code, data, and results are made publicly available.

How the architecture of gene regulatory networks ultimately shapes gene expression patterns is an open question, which has been approached from a multitude of angles. The dominant strategy has been to identify non-random features in these networks and then argue for the function of these features using mechanistic modelling. Here we establish the foundation of an alternative approach by studying the correlation of eigenvectors with synthetic gene expression data simulated with a basic and popular model of gene expression dynamics -- attractors of Boolean threshold dynamics in signed directed graphs. Eigenvectors of the graph Laplacian are known to explain collective dynamical states (stationary patterns) in Turing dynamics on graphs. In this study, we show that eigenvectors can also predict collective states (attractors) for a markedly different type of dynamics, Boolean threshold dynamics, and category of graphs, signed directed graphs. However, the overall predictive power depends on details of the network architecture, in a predictable fashion. Our results are a set of statistical observations, providing the first systematic step towards a further theoretical understanding of the role of eigenvectors in dynamics on graphs.

Lycopene, rich in red, yellow, or orange-colored fruits and vegetables, is the most potent antioxidant among the other carotenoids available in human blood plasma. It is evident that regular lycopene intake can prevent chronic diseases like cardiovascular diseases, type-2 diabetes, hypertension, kidney diseases and cancer. However, thermal processing, light, oxygen, and enzymes in gastrointestinal tract (GIT) compromise the bioaccessibility and bioavailability of lycopene ingested through diet. Nanoencapsulation provides a potential platform to prevent lycopene from light, air oxygen, thermal processing and enzymatic activity of the human digestive system. Physicochemical properties evidenced to be the potential indicator for determining the bioaccessibility of encapsulated bioactive compounds like lycopene. By manipulating the size or hydrodynamic diameter, zeta potential value or stability, polydispersity index or homogeneity and functional activity or retention of antioxidant properties observed to be the most prominent physicochemical properties to evaluate beneficial effect of implementation of nanotechnology on bioaccessibility study. Moreover, the molecular mechanism of the bioavailability of nanoparticles is not yet to be understood due to lack of comprehensive design to identify nanoparticles' behaviors if ingested through oral route as functional food ingredients. This review paper aims to study and leverage existing techniques about how nanotechnology can be used and verified to identify the bioaccessibility of lycopene before using it as a functional food ingredient for therapeutic treatments.

Diabetes Mellitus has no permanent cure to date and is one of the leading causes of death globally. The alarming increase in diabetes calls for the need to take precautionary measures to avoid/predict the occurrence of diabetes. This paper proposes HealthEdge, a machine learning-based smart healthcare framework for type 2 diabetes prediction in an integrated IoT-edge-cloud computing system. Numerical experiments and comparative analysis were carried out between the two most used machine learning algorithms in the literature, Random Forest (RF) and Logistic Regression (LR), using two real-life diabetes datasets. The results show that RF predicts diabetes with 6% more accuracy on average compared to LR.

Music is increasingly being used as a therapeutic tool in the field of rehabilitation medicine and psychophysiology. One of the main key components of music is its temporal organization. The characteristics of neurocognitive processes during music perception of meter in different tempo variations technique have been studied by using the event-related potentials technique. The study involved 20 volunteers (6 men, the median age of the participants was 23 years). The participants were asked to listen to 4 experimental series that differed in tempo (fast vs. slow) and meter (duple vs. triple). Each series consisted of 625 audio stimuli, 85% of which were organized with a standard metric structure (standard stimulus) and 15% were organized with a modified metric structure (deviant stimulus). The results revealed that the type of metric structure influences the detection of the change in it. The analysis revealed that the N200 wave occurred significantly faster for stimuli with duple meter and fast tempo and was the slowest for stimuli with triple meter and fast pace.

The major histocompatibility complex (MHC) molecules, which bind peptides for presentation on the cell surface, play an important role in cell-mediated immunity. In light of developing databases and technologies over the years, significant progress has been made in research on peptide binding affinity calculation. Several in techniques have been developed to predict peptide binding to MHC class I. Most of the research on MHC Class I due to its nature brings better performance and more. Considering the use of different methods and different technologies, and the approach of similar methods on different proteins, a classification was created according to the binding affinity of protein peptides.

We present a proof based on SEIR-models that shows it is impossible to identify the level of under reporting based on traditional observables of the disease dynamics alone. This means that the true attack rate must be determined through other means.

The depth of knowledge offered by post-genomic medicine has carried the promise of new drugs, and cures for multiple diseases. To explore the degree to which this capability has materialized, we extract meta-data from 356,403 clinical trials spanning four decades, aiming to offer mechanistic insights into the innovation practices in drug discovery. We find that convention dominates over innovation, as over 96% of the recorded trials focus on previously tested drug targets, and the tested drugs target only 12% of the human interactome. If current patterns persist, it would take 170 years to target all druggable proteins. We uncover two network-based fundamental mechanisms that currently limit target discovery: preferential attachment, leading to the repeated exploration of previously targeted proteins; and local network effects, limiting exploration to proteins interacting with highly explored proteins. We build on these insights to develop a quantitative network-based model of drug discovery. We demonstrate that the model is able to accurately recreate the exploration patterns observed in clinical trials. Most importantly, we show that a network-based search strategy can widen the scope of drug discovery by guiding exploration to novel proteins that are part of under explored regions in the human interactome.