The moral machine experiment on large language models.

As large language models (LLMs) have become more deeply integrated into various sectors, understanding how they make moral judgements has become crucial, particularly in the realm of autonomous driving. This study used the moral machine framework to investigate the ethical decision-making tendencies of prominent LLMs, including GPT-3.5, GPT-4, PaLM 2 and Llama 2, to compare their responses with human preferences. While LLMs' and humans' preferences such as prioritizing humans over pets and favouring saving more lives are broadly aligned, PaLM 2 and Llama 2, especially, evidence distinct deviations. Additionally, despite the qualitative similarities between the LLM and human preferences, there are significant quantitative disparities, suggesting that LLMs might lean toward more uncompromising decisions, compared with the milder inclinations of humans. These insights elucidate the ethical frameworks of LLMs and their potential implications for autonomous driving.

Revisiting the political biases of ChatGPT.

Although ChatGPT promises wide-ranging applications, there is a concern that it is politically biased; in particular, that it has a left-libertarian orientation. Nevertheless, following recent trends in attempts to reduce such biases, this study re-evaluated the political biases of ChatGPT using political orientation tests and the application programming interface. The effects of the languages used in the system as well as gender and race settings were evaluated. The results indicate that ChatGPT manifests less political bias than previously assumed; however, they did not entirely dismiss the political bias. The languages used in the system, and the gender and race settings may induce political biases. These findings enhance our understanding of the political biases of ChatGPT and may be useful for bias evaluation and designing the operational strategy of ChatGPT.

Adversarial attacks on voter model dynamics in complex networks.

This paper investigates adversarial attacks conducted to distort voter model dynamics in complex networks. Specifically, a simple adversarial attack method is proposed to hold the state of opinions of an individual closer to the target state in the voter model dynamics. This indicates that even when one opinion is the majority the vote outcome can be inverted (i.e., the outcome can lean toward the other opinion) by adding extremely small (hard-to-detect) perturbations strategically generated in social networks. Adversarial attacks are relatively more effective in complex (large and dense) networks. These results indicate that opinion dynamics can be unknowingly distorted.

Universal adversarial attacks on deep neural networks for medical image classification.

BACKGROUND: Deep neural networks (DNNs) are widely investigated in medical image classification to achieve automated support for clinical diagnosis. It is necessary to evaluate the robustness of medical DNN tasks against adversarial attacks, as high-stake decision-making will be made based on the diagnosis. Several previous studies have considered simple adversarial attacks. However, the vulnerability of DNNs to more realistic and higher risk attacks, such as universal adversarial perturbation (UAP), which is a single perturbation that can induce DNN failure in most classification tasks has not been evaluated yet. METHODS: We focus on three representative DNN-based medical image classification tasks (i.e., skin cancer, referable diabetic retinopathy, and pneumonia classifications) and investigate their vulnerability to the seven model architectures of UAPs. RESULTS: We demonstrate that DNNs are vulnerable to both nontargeted UAPs, which cause a task failure resulting in an input being assigned an incorrect class, and to targeted UAPs, which cause the DNN to classify an input into a specific class. The almost imperceptible UAPs achieved > 80% success rates for nontargeted and targeted attacks. The vulnerability to UAPs depended very little on the model architecture. Moreover, we discovered that adversarial retraining, which is known to be an effective method for adversarial defenses, increased DNNs' robustness against UAPs in only very few cases. CONCLUSION: Unlike previous assumptions, the results indicate that DNN-based clinical diagnosis is easier to deceive because of adversarial attacks. Adversaries can cause failed diagnoses at lower costs (e.g., without consideration of data distribution); moreover, they can affect the diagnosis. The effects of adversarial defenses may not be limited. Our findings emphasize that more careful consideration is required in developing DNNs for medical imaging and their practical applications.

Vulnerability of deep neural networks for detecting COVID-19 cases from chest X-ray images to universal adversarial attacks.

Owing the epidemic of the novel coronavirus disease 2019 (COVID-19), chest X-ray computed tomography imaging is being used for effectively screening COVID-19 patients. The development of computer-aided systems based on deep neural networks (DNNs) has become an advanced open source to rapidly and accurately detect COVID-19 cases because the need for expert radiologists, who are limited in number, forms a bottleneck for screening. However, thus far, the vulnerability of DNN-based systems has been poorly evaluated, although realistic and high-risk attacks using universal adversarial perturbation (UAP), a single (input image agnostic) perturbation that can induce DNN failure in most classification tasks, are available. Thus, we focus on representative DNN models for detecting COVID-19 cases from chest X-ray images and evaluate their vulnerability to UAPs. We consider non-targeted UAPs, which cause a task failure, resulting in an input being assigned an incorrect label, and targeted UAPs, which cause the DNN to classify an input into a specific class. The results demonstrate that the models are vulnerable to non-targeted and targeted UAPs, even in the case of small UAPs. In particular, the 2% norm of the UAPs to the average norm of an image in the image dataset achieves >85% and >90% success rates for the non-targeted and targeted attacks, respectively. Owing to the non-targeted UAPs, the DNN models judge most chest X-ray images as COVID-19 cases. The targeted UAPs allow the DNN models to classify most chest X-ray images into a specified target class. The results indicate that careful consideration is required in practical applications of DNNs to COVID-19 diagnosis; in particular, they emphasize the need for strategies to address security concerns. As an example, we show that iterative fine-tuning of DNN models using UAPs improves the robustness of DNN models against UAPs.

The brain-derived neurotrophic factor Val66Met polymorphism increases segregation of structural correlation networks in healthy adult brains.

BACKGROUND: Although structural correlation network (SCN) analysis is an approach to evaluate brain networks, the neurobiological interpretation of SCNs is still problematic. Brain-derived neurotrophic factor (BDNF) is well-established as a representative protein related to neuronal differentiation, maturation, and survival. Since a valine-to-methionine substitution at codon 66 of the BDNF gene (BDNF Val66Met single nucleotide polymorphism (SNP)) is well-known to have effects on brain structure and function, we hypothesized that SCNs are affected by the BDNF Val66Met SNP. To gain insight into SCN analysis, we investigated potential differences between BDNF valine (Val) homozygotes and methionine (Met) carriers in the organization of their SCNs derived from inter-regional cortical thickness correlations. METHODS: Forty-nine healthy adult subjects (mean age = 41.1 years old) were divided into two groups according to their genotype (n: Val homozygotes = 16, Met carriers = 33). We obtained regional cortical thickness from their brain T1 weighted images. Based on the inter-regional cortical thickness correlations, we generated SCNs and used graph theoretical measures to assess differences between the two groups in terms of network integration, segregation, and modularity. RESULTS: The average local efficiency, a measure of network segregation, of BDNF Met carriers' network was significantly higher than that of the Val homozygotes' (permutation p-value = 0.002). Average shortest path lengths (a measure of integration), average local clustering coefficient (another measure of network segregation), small-worldness (a balance between integration and segregation), and modularity (a representative measure for modular architecture) were not significantly different between group (permutation p-values ≧ 0.01). DISCUSSION AND CONCLUSION: Our results suggest that the BDNF Val66Met polymorphism may potentially influence the pattern of brain regional morphometric (cortical thickness) correlations. Comparing networks derived from inter-regional cortical thickness correlations, Met carrier SCNs have denser connections with neighbors and are more distant from random networks than Val homozygote networks. Thus, it may be necessary to consider potential effects of BDNF gene mutations in SCN analyses. This is the first study to demonstrate a difference between Val homozygotes and Met carriers in brain SCNs.

Revisiting the hypothesis of an energetic barrier to genome complexity between eukaryotes and prokaryotes.

The absence of genome complexity in prokaryotes, being the evolutionary precursors to eukaryotic cells comprising all complex life (the prokaryote-eukaryote divide), is a long-standing question in evolutionary biology. A previous study hypothesized that the divide exists because prokaryotic genome size is constrained by bioenergetics (prokaryotic power per gene or genome being significantly lower than eukaryotic ones). However, this hypothesis was evaluated using a relatively small dataset due to lack of data availability at the time, and is therefore controversial. Accordingly, we constructed a larger dataset of genomes, metabolic rates, cell sizes and ploidy levels to investigate whether an energetic barrier to genome complexity exists between eukaryotes and prokaryotes while statistically controlling for the confounding effects of cell size and phylogenetic signals. Notably, we showed that the differences in bioenergetics between prokaryotes and eukaryotes were less significant than those previously reported. More importantly, we found a limited contribution of power per genome and power per gene to the prokaryote-eukaryote dichotomy. Our findings indicate that the prokaryote-eukaryote divide is hard to explain from the energetic perspective. However, our findings may not entirely discount the traditional hypothesis; in contrast, they indicate the need for more careful examination.

Difficulty in inferring microbial community structure based on co-occurrence network approaches.

BACKGROUND: Co-occurrence networks-ecological associations between sampled populations of microbial communities inferred from taxonomic composition data obtained from high-throughput sequencing techniques-are widely used in microbial ecology. Several co-occurrence network methods have been proposed. Co-occurrence network methods only infer ecological associations and are often used to discuss species interactions. However, validity of this application of co-occurrence network methods is currently debated. In particular, they simply evaluate using parametric statistical models, even though microbial compositions are determined through population dynamics. RESULTS: We comprehensively evaluated the validity of common methods for inferring microbial ecological networks through realistic simulations. We evaluated how correctly nine widely used methods describe interaction patterns in ecological communities. Contrary to previous studies, the performance of the co-occurrence network methods on compositional data was almost equal to or less than that of classical methods (e.g., Pearson's correlation). The methods described the interaction patterns in dense and/or heterogeneous networks rather inadequately. Co-occurrence network performance also depended upon interaction types; specifically, the interaction patterns in competitive communities were relatively accurately predicted while those in predator-prey (parasitic) communities were relatively inadequately predicted. CONCLUSIONS: Our findings indicated that co-occurrence network approaches may be insufficient in interpreting species interactions in microbiome studies. However, the results do not diminish the importance of these approaches. Rather, they highlight the need for further careful evaluation of the validity of these much-used methods and the development of more suitable methods for inferring microbial ecological networks.

Brain structural connectivity and neuroticism in healthy adults.

Understanding the neural correlates of the neurotic brain is important because neuroticism is a risk factor for the development of psychopathology. We examined the correlation between brain structural networks and neuroticism based on NEO Five-Factor Inventory (NEO-FFI) scores. Fifty-one healthy participants (female, n = 18; male, n = 33; mean age, 38.5 ± 11.7 years) underwent the NEO-FFI test and magnetic resonance imaging (MRI), including diffusion tensor imaging and 3D T1WI. Using MRI data, for each participant, we constructed whole-brain interregional connectivity matrices by deterministic tractography and calculated the graph theoretical network measures, including the characteristic path length, global clustering coefficient, small-worldness, and betweenness centrality (BET) in 83 brain regions from the Desikan-Killiany atlas with subcortical segmentation using FreeSurfer. In relation to the BET, neuroticism score had a negative correlation in the left isthmus cingulate cortex, left superior parietal, left superior temporal, right caudal middle frontal, and right entorhinal cortices, and a positive correlation in the bilateral frontal pole, left caudal anterior cingulate cortex, and left fusiform gyrus. No other measurements showed significant correlations. Our results imply that the brain regions related to neuroticism exist in various regions, and that the neuroticism trait is likely formed as a result of interactions among these regions. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network) from the Ministry of Education, Science, Sports and Culture of Japan.

Decomposing the effects of ocean environments on predator-prey body-size relationships in food webs.

Body-size relationships between predators and their prey are important in ecological studies because they reflect the structure and function of food webs. Inspired by studies on the impact of global warming on food webs, the effects of temperature on body-size relationships have been widely investigated; however, the impact of environmental factors on body-size relationships has not been fully evaluated because climate warming affects various ocean environments. Thus, here, we comprehensively investigated the effects of ocean environments and predator-prey body-size relationships by integrating a large-scale dataset of predator-prey body-size relationships in marine food webs with global oceanographic data. We showed that various oceanographic parameters influence prey size selection. In particular, oxygen concentration, primary production and salinity, in addition to temperature, significantly alter body-size relationships. Furthermore, we demonstrated that variability (seasonality) of ocean environments significantly affects body-size relationships. The effects of ocean environments on body-size relationships were generally remarkable for small body sizes, but were also significant for large body sizes and were relatively weak for intermediate body sizes, in the cases of temperature seasonality, oxygen concentration and salinity variability. These findings break down the complex effects of ocean environments on body-size relationships, advancing our understanding of how ocean environments influence the structure and functioning of food webs.

MAPLE 2.3.0: an improved system for evaluating the functionomes of genomes and metagenomes.

MAPLE is an automated system for inferring the potential comprehensive functions harbored by genomes and metagenomes. To reduce runtime in MAPLE analyzing the massive amino acid datasets of over 1 million sequences, we improved it by adapting the KEGG automatic annotation server to use GHOSTX and verified no substantial difference in the MAPLE results between the original and new implementations.

PREvaIL, an integrative approach for inferring catalytic residues using sequence, structural, and network features in a machine-learning framework.

Determining the catalytic residues in an enzyme is critical to our understanding the relationship between protein sequence, structure, function, and enhancing our ability to design novel enzymes and their inhibitors. Although many enzymes have been sequenced, and their primary and tertiary structures determined, experimental methods for enzyme functional characterization lag behind. Because experimental methods used for identifying catalytic residues are resource- and labor-intensive, computational approaches have considerable value and are highly desirable for their ability to complement experimental studies in identifying catalytic residues and helping to bridge the sequence-structure-function gap. In this study, we describe a new computational method called PREvaIL for predicting enzyme catalytic residues. This method was developed by leveraging a comprehensive set of informative features extracted from multiple levels, including sequence, structure, and residue-contact network, in a random forest machine-learning framework. Extensive benchmarking experiments on eight different datasets based on 10-fold cross-validation and independent tests, as well as side-by-side performance comparisons with seven modern sequence- and structure-based methods, showed that PREvaIL achieved competitive predictive performance, with an area under the receiver operating characteristic curve and area under the precision-recall curve ranging from 0.896 to 0.973 and from 0.294 to 0.523, respectively. We demonstrated that this method was able to capture useful signals arising from different levels, leveraging such differential but useful types of features and allowing us to significantly improve the performance of catalytic residue prediction. We believe that this new method can be utilized as a valuable tool for both understanding the complex sequence-structure-function relationships of proteins and facilitating the characterization of novel enzymes lacking functional annotations.

Large-scale aggregation analysis of eukaryotic proteins reveals an involvement of intrinsically disordered regions in protein folding.

A subset of the proteome is prone to aggregate formation, which is prevented by chaperones in the cell. To investigate whether the basic principle underlying the aggregation process is common in prokaryotes and eukaryotes, we conducted a large-scale aggregation analysis of ~500 cytosolic budding yeast proteins using a chaperone-free reconstituted translation system, and compared the obtained data with that of ~3,000 Escherichia coli proteins reported previously. Although the physicochemical properties affecting the aggregation propensity were generally similar in yeast and E. coli proteins, the susceptibility of aggregation in yeast proteins were positively correlated with the presence of intrinsically disordered regions (IDRs). Notably, the aggregation propensity was not significantly changed by a removal of IDRs in model IDR-containing proteins, suggesting that the properties of ordered regions in these proteins are the dominant factors for aggregate formation. We also found that the proteins with longer IDRs were disfavored by E. coli chaperonin GroEL/ES, whereas both bacterial and yeast Hsp70/40 chaperones have a strong aggregation-prevention effect even for proteins possessing IDRs. These results imply that a key determinant to discriminate the eukaryotic proteomes from the prokaryotic proteomes in terms of protein folding would be the attachment of IDRs.

Network resilience of mutualistic ecosystems and environmental changes: an empirical study.

It is theorized that a mutualistic ecosystem's resilience against perturbations (e.g. species extinction) is determined by a single macroscopic parameter (network resilience), calculable from the network. Given that such perturbations occur owing to environmental changes (e.g. climate change and human impact), it has been predicted that mutualistic ecosystems that exist despite extensive environmental changes exhibit higher network resilience; however, such a prediction has not been confirmed using real-world data. Thus, in this study, the effects of climate change velocity and human activities on mutualistic network resilience were investigated. A global dataset of plant-animal mutualistic networks was used, and spatial analysis was performed to examine the effects. Moreover, the potential confounding effects of network size, current climate and altitude were statistically controlled. It was demonstrated that mutualistic network resilience was globally influenced by warming velocity and human impact, in addition to current climate. Specifically, pollination network resilience increased in response to human impact, and seed-dispersal network resilience increased with warming velocity. The effect of environmental changes on network resilience for plants was remarkable. The results confirmed the prediction obtained based on the theory and imply that real-world mutualistic networks have a structure that increases ecosystem resilience against environmental changes. These findings will enhance the understanding of ecosystem resilience.

Limitations of a metabolic network-based reverse ecology method for inferring host-pathogen interactions.

BACKGROUND: Host-pathogen interactions are important in a wide range of research fields. Given the importance of metabolic crosstalk between hosts and pathogens, a metabolic network-based reverse ecology method was proposed to infer these interactions. However, the validity of this method remains unclear because of the various explanations presented and the influence of potentially confounding factors that have thus far been neglected. RESULTS: We re-evaluated the importance of the reverse ecology method for evaluating host-pathogen interactions while statistically controlling for confounding effects using oxygen requirement, genome, metabolic network, and phylogeny data. Our data analyses showed that host-pathogen interactions were more strongly influenced by genome size, primary network parameters (e.g., number of edges), oxygen requirement, and phylogeny than the reserve ecology-based measures. CONCLUSION: These results indicate the limitations of the reverse ecology method; however, they do not discount the importance of adopting reverse ecology approaches altogether. Rather, we highlight the need for developing more suitable methods for inferring host-pathogen interactions and conducting more careful examinations of the relationships between metabolic networks and host-pathogen interactions.

Exosomes in mammals with greater habitat variability contain more proteins and RNAs.

Factors determining habitat variability are poorly understood despite possible explanations based on genome and physiology. This is because previous studies only focused on primary measures such as genome size and body size. In this study, we hypothesize that specific gene functions determine habitat variability in order to explore new factors beyond primary measures. We comprehensively evaluate the relationship between gene functions and the climate envelope while statistically controlling for potentially confounding effects by using data on the habitat range, genome, body size and metabolism of various mammals. Our analyses show that the number of proteins and RNAs contained in exosomes is predominantly associated with the climate envelope. This finding indicates the importance of exosomes to habitat range expansion of mammals and provides a new hypothesis for the relationship between the genome and habitat variability.

Data integration aids understanding of butterfly-host plant networks.

Although host-plant selection is a central topic in ecology, its general underpinnings are poorly understood. Here, we performed a case study focusing on the publicly available data on Japanese butterflies. A combined statistical analysis of plant-herbivore relationships and taxonomy revealed that some butterfly subfamilies in different families feed on the same plant families, and the occurrence of this phenomenon more than just by chance, thus indicating the independent acquisition of adaptive phenotypes to the same hosts. We consequently integrated plant-herbivore and plant-compound relationship data and conducted a statistical analysis to identify compounds unique to host plants of specific butterfly families. Some of the identified plant compounds are known to attract certain butterfly groups while repelling others. The additional incorporation of insect-compound relationship data revealed potential metabolic processes that are related to host plant selection. Our results demonstrate that data integration enables the computational detection of compounds putatively involved in particular interspecies interactions and that further data enrichment and integration of genomic and transcriptomic data facilitates the unveiling of the molecular mechanisms involved in host plant selection.

Importance of metabolic rate to the relationship between the number of genes in a functional category and body size in Peto's paradox for cancer.

Elucidation of tumour suppression mechanisms is a major challenge in cancer biology. Therefore, Peto's paradox, or low cancer incidence in large animals, has attracted focus. According to the gene-abundance hypothesis, which considers the increase/decrease in cancer-related genes with body size, researchers evaluated the associations between gene abundance and body size. However, previous studies only focused on a few specific gene functions and have ignored the alternative hypothesis (metabolic rate hypothesis): in this hypothesis, the cellular metabolic rate and subsequent oxidative stress decreases with increasing body size. In this study, we have elected to explore the gene-abundance hypothesis taking into account the metabolic rate hypothesis. Thus, we comprehensively investigated the correlation between the number of genes in various functional categories and body size while at the same time correcting for the mass-specific metabolic rate (Bc). A number of gene functions that correlated with body size were initially identified, but they were found to be artefactual due to the decrease in Bc with increasing body size. By contrast, immune system-related genes were found to increase with increasing body size when the correlation included this correction for Bc. These findings support the gene-abundance hypothesis and emphasize the importance of also taking into account the metabolic rate when evaluating gene abundance-body size relationships. This finding may be useful for understanding cancer evolution and tumour suppression mechanisms as well as for determining cancer-related genes and functions.

An automated system for evaluation of the potential functionome: MAPLE version 2.1.0.

Metabolic and physiological potential evaluator (MAPLE) is an automatic system that can perform a series of steps used in the evaluation of potential comprehensive functions (functionome) harboured in the genome and metagenome. MAPLE first assigns KEGG Orthology (KO) to the query gene, maps the KO-assigned genes to the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional modules, and then calculates the module completion ratio (MCR) of each functional module to characterize the potential functionome in the user's own genomic and metagenomic data. In this study, we added two more useful functions to calculate module abundance and Q-value, which indicate the functional abundance and statistical significance of the MCR results, respectively, to the new version of MAPLE for more detailed comparative genomic and metagenomic analyses. Consequently, MAPLE version 2.1.0 reported significant differences in the potential functionome, functional abundance, and diversity of contributors to each function among four metagenomic datasets generated by the global ocean sampling expedition, one of the most popular environmental samples to use with this system. MAPLE version 2.1.0 is now available through the web interface (http://www.genome.jp/tools/maple/) 17 June 2016, date last accessed.

Human Impacts and Climate Change Influence Nestedness and Modularity in Food-Web and Mutualistic Networks.

Theoretical studies have indicated that nestedness and modularity-non-random structural patterns of ecological networks-influence the stability of ecosystems against perturbations; as such, climate change and human activity, as well as other sources of environmental perturbations, affect the nestedness and modularity of ecological networks. However, the effects of climate change and human activities on ecological networks are poorly understood. Here, we used a spatial analysis approach to examine the effects of climate change and human activities on the structural patterns of food webs and mutualistic networks, and found that ecological network structure is globally affected by climate change and human impacts, in addition to current climate. In pollination networks, for instance, nestedness increased and modularity decreased in response to increased human impacts. Modularity in seed-dispersal networks decreased with temperature change (i.e., warming), whereas food web nestedness increased and modularity declined in response to global warming. Although our findings are preliminary owing to data-analysis limitations, they enhance our understanding of the effects of environmental change on ecological communities.