GraphIX: Graph-based In silico XAI(explainable artificial intelligence) for drug repositioning from biopharmaceutical network

Drug repositioning holds great promise because it can reduce the time and cost of new drug development. While drug repositioning can omit various R&D processes, confirming pharmacological effects on biomolecules is essential for application to new diseases. Biomedical explainability in a drug repositioning model can support appropriate insights in subsequent in-depth studies. However, the validity of the XAI methodology is still under debate, and the effectiveness of XAI in drug repositioning prediction applications remains unclear. In this study, we propose GraphIX, an explainable drug repositioning framework using biological networks, and quantitatively evaluate its explainability. GraphIX first learns the network weights and node features using a graph neural network from known drug indication and knowledge graph that consists of three types of nodes (but not given node type information): disease, drug, and protein. Analysis of the post-learning features showed that node types that were not known to the model beforehand are distinguished through the learning process based on the graph structure. From the learned weights and features, GraphIX then predicts the disease-drug association and calculates the contribution values of the nodes located in the neighborhood of the predicted disease and drug. We hypothesized that the neighboring protein node to which the model gave a high contribution is important in understanding the actual pharmacological effects. Quantitative evaluation of the validity of protein nodes' contribution using a real-world database showed that the high contribution proteins shown by GraphIX are reasonable as a mechanism of drug action. GraphIX is a framework for evidence-based drug discovery that can present to users new disease-drug associations and identify the protein important for understanding its pharmacological effects from a large and complex knowledge base.Comment: add supplementary material

Discriminative application of string similarity methods to chemical and non-chemical names for biomedical abbreviation clustering

BACKGROUND: Various computational methods are presently available to classify whether a protein variation is disease-associated or not. However data derived from recent technological advancements make it feasible to extend the annotation of disease-associated variations in order to include specific phenotypes. Here we tackle the problem of distinguishing between genetic variations associated to cancer and variations associated to other genetic diseases. RESULTS: We implement a new method based on Support Vector Machines that takes as input the protein variant and the protein function, as described by its associated Gene Ontology terms. Our approach succeeds in discriminating between germline variants that are likely to be cancer-associated from those that are related to other genetic disorders. The method performs with values of 90% accuracy and 0.61 Matthews correlation coefficient on a set comprising 6478 germline variations (16% are cancer-associated) in 592 proteins. The sensitivity and the specificity on the cancer class are 69% and 66%, respectively. Furthermore the method is capable of correctly excluding some 96% of 3392 somatic cancer-associated variations in 1983 proteins not included in the training/testing set. CONCLUSIONS: Here we prove feasible that a large set of cancer associated germline protein variations can be successfully discriminated from those associated to other genetic disorders. This is a step further in the process of protein variant annotation. Scoring largely improves when protein function as encoded by Gene Ontology terms is considered, corroborating the role of protein function as a key feature for a correct annotation of its variations

Socio-spatial cognition in cats: Mentally mapping owner’s location from voice

予期せぬ場所から聞こえる飼い主の声にびっくり --ネコは耳で飼い主の位置を捉えている--. 京都大学プレスリリース. 2021-11-22.Many animals probably hold mental representations about the whereabouts of others; this is a form of socio-spatial cognition. We tested whether cats mentally map the spatial position of their owner or a familiar cat to the source of the owner’s or familiar cat’s vocalization. In Experiment 1, we placed one speaker outside a familiar room (speaker 1) and another (speaker 2) inside the room, as far as possible from speaker 1, then we left the subject alone in the room. In the habituation phase, the cat heard its owner’s voice calling its name five times from speaker 1. In the test phase, shortly after the 5th habituation phase vocalization, one of the two speakers played either the owner’s voice or a stranger’s voice calling the cat’s name once. There were four test combinations of speaker location and sound: Same[sound] Same[location], Same[sound] Diff[location], Diff[sound] Same[location], Diff[sound] Diff[location]. In line with our prediction, cats showed most surprise in the Same[sound] Diff[location] condition, where the owner suddenly seemed to be in a new place. This reaction disappeared when we used cat vocalizations (Experiment 2) or non-vocal sounds (Experiment 3) as the auditory stimuli. Our results suggest that cats have mental representations about their out-of-sight owner linked to hearing the owner’s voice, indicating a previously unidentified socio-spatial cognitive ability

Effect of Body Size and Sugar Meals on Oviposition of the Yellow Fever Mosquito, Aedes aegypti (Diptera: Culicidae)

The effects of dietary sugar and body size on the oviposition of Ae. aegypti were studied under laboratory conditions. In female mosquitoes provided with sugar, the start of maximum fecundity was significantly delayed and the oviposition period was longer than in females provided with water. The peak of oviposition was also delayed in sugar-fed females. Large females oviposited more eggs per day than small females at maximum fecundity and during eight days of observations. Large females also visited significantly more water-containing cups in their cages per day than small females at maximum fecundity. During the eight days of observations, large females and sugar-fed females visited more watercontaining cups in their cages than water-fed small females. Both large females and sugar-fed females oviposited their eggs at sites higher above the water line than water-fed small females. These results suggested that large and sugar-fed female Ae. aegypti mosquitoes had more energy reserves and oviposited their eggs at higher sites, which would lead to a time lag in hatching

Effect of Digestibility of Soy Protein Concentrate on Rat Nutrition(1) : Effect of Proteolytic Pretreatment of Soy Protein Concentrate on Amino Acid Pattern in Small Intestine and Activities of Enzymes related with Digestion and Metabolism of Protein

The digestion and metabolism of protein of rats fed soy protein concentrate (SP) pretreated by protease was investigated, and the nutritive value of the pretreated SP was discussed. Glutamate-pyruvate transaminase, arginase and xanthine oxidase activities in liver of rats fed heated SP are lower than those fed SP pretreated by protease and amino acid mixture simulated SP. There is more quantity of peptide in small intestine of rats fed SP pretreated by protease than that fed the amino acid mixture. In free amino acid pattern, however, no difference was shown between SP groups, but the patterns of SP groups, especially on the bases of methionine content, were different with that of amino acid mixture group. No difference is shown in the digestion and the biological values between SP groups. From these results, it was found that the pretreatment of SP by protease, which might improve the digestibility of SP, was effective for raising the availability of SP. It may be considered, furthermore, that methionine in SP is difficult to liberate in small intestine, which causes a wasteful absorption of amino acids for rat

Lead exposure assessment among pregnant women, newborns, and children: case study from Karachi, Pakistan.

Lead (Pb) in petrol has been banned in developed countries. Despite the control of Pb in petrol since 2001, high levels were reported in the blood of pregnant women and children in Pakistan. However, the identification of sources of Pb has been elusive due to its pervasiveness. In this study, we assessed the lead intake of pregnant women and one- to three-year-old children from food, water, house dust, respirable dust, and soil. In addition, we completed the fingerprinting of the Pb isotopic ratios (LIR) of petrol and secondary sources (food, house-dust, respirable dust, soil, surma (eye cosmetics)) of exposure within the blood of pregnant women, newborns, and children. Eight families, with high (~50 μg/dL), medium (~20 μg/dL), and low blood levels (~10 μg/dL), were selected from 60 families. The main sources of exposure to lead for children were food and house-dust, and those for pregnant women were soil, respirable dust, and food. LIR was determined by inductively coupled plasma quadrupole mass spectrometry (ICP-QMS) with a two sigma uncertainty of ±0.03%. The LIR of mothers and newborns was similar. In contrast, surma, and to a larger extent petrol, exhibited a negligible contribution to both the child’s and mother’s blood Pb. Household wet-mopping could be effective in reducing Pb exposure. This intake assessment could be replicated for other developing countries to identify sources of lead and the burden of lead exposure in the population