Human Diversity Research Articles

7939 Impact of genetic background on chronic inflammation in a letrozole-induced mouse model of PCOS

Abstract Disclosure: N. Ujagar: None. G. De Robles: None. L.M. Velez: None. M. Seldin: None. D. Nicholas: None. The etiology behind polycystic ovary syndrome (PCOS) is elusive due to the heterogeneity of its symptoms and varying severity in patients. There are a wide variety of factors associated with PCOS, like hyperinsulinemia, hyperandrogenism, endotoxemia and chronic inflammation that have been implicated as causal factors in the condition. However mechanisms of cause and effect are difficult to establish in human cohorts. Endotoxemia, observed in humans and mouse models of PCOS, is known to trigger chronic inflammation by activating immune cells. Although correlation of chronic inflammation with PCOS has been established, the type of inflammation in PCOS patients has not been defined, in part due to the genetic variance from person to person. Using a systems immunology approach to mimic human genetic diversity, combined with a letrozole-induced PCOS mouse model, we aim to distinguish the types of inflammation present in PCOS. We analyzed the immune cells from lymph nodes and spleens of 21 different strains of PCOS induced and control mice (130 mice in total), and found that based on genetic background the reproductive and metabolic phenotypes differed- similar to how PCOS presents clinically. We were able to categorize each letrozole-induced mouse strain into the sub-phenotypes of PCOS based on the current guidelines for diagnosing PCOS published in 2023 and extensive characterization of each strain. Splenocytes from these control and PCOS mice were activated in vitro to trigger T cell and myeloid cell cytokine secretion, which was measured via luminex. Clustering analysis of these multi-analyte cytokine measurements together with flow cytometry of the immune cells allowed us to identify T-helper 17 (Th17) cells as the prominent immune cell driving inflammation in letrozole-induce mouse model of PCOS independent of genetic background. This systems immunology approach has allowed us to define PCOS associated inflammation and will be the basis for integrating human inflammation in PCOS with mouse models that appropriately recapitulate disease. The discovery of Th17 cells as key inflammatory mediators provide targets for understanding the mechanisms linking chronic inflammation to reproductive and metabolic outcomes in PCOS, and will assist in future development of anti-inflammatory therapies. Presentation: 6/2/2024

7939 Impact of genetic background on chronic inflammation in a letrozole-induced mouse model of PCOS

Abstract Disclosure: N. Ujagar: None. G. De Robles: None. L.M. Velez: None. M. Seldin: None. D. Nicholas: None. The etiology behind polycystic ovary syndrome (PCOS) is elusive due to the heterogeneity of its symptoms and varying severity in patients. There are a wide variety of factors associated with PCOS, like hyperinsulinemia, hyperandrogenism, endotoxemia and chronic inflammation that have been implicated as causal factors in the condition. However mechanisms of cause and effect are difficult to establish in human cohorts. Endotoxemia, observed in humans and mouse models of PCOS, is known to trigger chronic inflammation by activating immune cells. Although correlation of chronic inflammation with PCOS has been established, the type of inflammation in PCOS patients has not been defined, in part due to the genetic variance from person to person. Using a systems immunology approach to mimic human genetic diversity, combined with a letrozole-induced PCOS mouse model, we aim to distinguish the types of inflammation present in PCOS. We analyzed the immune cells from lymph nodes and spleens of 21 different strains of PCOS induced and control mice (130 mice in total), and found that based on genetic background the reproductive and metabolic phenotypes differed- similar to how PCOS presents clinically. We were able to categorize each letrozole-induced mouse strain into the sub-phenotypes of PCOS based on the current guidelines for diagnosing PCOS published in 2023 and extensive characterization of each strain. Splenocytes from these control and PCOS mice were activated in vitro to trigger T cell and myeloid cell cytokine secretion, which was measured via luminex. Clustering analysis of these multi-analyte cytokine measurements together with flow cytometry of the immune cells allowed us to identify T-helper 17 (Th17) cells as the prominent immune cell driving inflammation in letrozole-induce mouse model of PCOS independent of genetic background. This systems immunology approach has allowed us to define PCOS associated inflammation and will be the basis for integrating human inflammation in PCOS with mouse models that appropriately recapitulate disease. The discovery of Th17 cells as key inflammatory mediators provide targets for understanding the mechanisms linking chronic inflammation to reproductive and metabolic outcomes in PCOS, and will assist in future development of anti-inflammatory therapies. Presentation: 6/2/2024

Challenges and Opportunities for Psychological Research in the Majority World

How can psychology transform itself into an inclusive science that engages with the rich cultural diversity of humanity? How can we strive towards a broader and deeper understanding of human behavior that is both generalizable across populations and attentive to its diversity? To address these major questions of our field, relying on scholars from different world regions, we outline first the opportunities associated with conducting psychological research in these and other majority world regions, highlighting international collaborations. Cross-cutting research themes in psychological research in the majority world are presented along with the urgent need to adopt a more critical lens to research and knowledge production within psychology. Indigenization, critical, transformative and liberatory approaches to understanding psychological phenomena framed within the decolonial imperative are presented as future options for a more diverse and equitable psychological science. Next, we address challenges, including limited institutional research infrastructure, limited national investment in research, political and social challenges these regions face, and the impact of imported (rather than locally produced) psychological knowledge. We conclude by offering recommendations to enable psychological science to be more representative of the world’s population. Our aim is to facilitate a broader, better-informed, and more empathic conversation among psychological scientists worldwide about ways to make psychological science more representative, culturally informed and inclusive.

Diversification of Antibodies: From V(D)J Recombination to Somatic Exon Shuffling.

Antibodies that gain specificity by a large insert encoding for an extra domain were described for the first time in 2016. In malaria-exposed individuals, an exon deriving from the leukocyte-associated immunoglobulin-like 1 (LAIR1) gene integrated via a copy-and-paste insertion into the immunoglobulin heavy chain encoding region. A few years later, a second example was identified, namely a dual exon integration from the leukocyte immunoglobulin-like receptor B1 (LILRB1) gene that is located in close proximity to LAIR1. A dedicated high-throughput characterization of chimeric immunoglobulin heavy chain transcripts unraveled, that insertions from distant genomic regions (including mitochondrial DNA) can contribute to human antibody diversity. This review describes the modalities of insert-containing antibodies. The role of known DNA mobility aspects, such as genomic translocation, gene conversion, and DNA fragility, is discussed in the context of insert-antibody generation. Finally, the review covers why insert antibodies were omitted from the past repertoire analyses and how insert antibodies can contribute to protective immunity or an autoreactive response.

Refugees’ employment: Adapting a structural inequality framework for multinational corporations

Multinational corporations (MNCs), through action or inaction, directly and indirectly shape vertical, horizontal, or internal structural inequalities in labour markets. The refugee employment literature has given scant attention to the role of MNCs, and how these corporations can or do contribute to achieving equality in employment outcomes for diverse social groups such as refugees. In this paper, we explore how MNCs seek to address challenges associated with structural inequalities to achieve greater equality in employment outcomes for refugees. To do so, we draw on the refugee employment literature, industry evidence, and business reports. Our findings reveal that MNCs require global and national-level responses to address structural inequalities associated with vertical, horizontal, or internal inequalities. We synthesise these inequalities into a conceptual framework and illustrate the need for MNCs to balance standardisation vs localisation strategies in human resource and diversity management, sourcing and supply chain management, corporate social responsibility, marketing and branding, and external engagement. Such MNC strategies contribute to refugees’ ability to navigate structural factors that create employment inequalities.

Impact of Human Immunological Responses and Viral Genetic Diversity on Outbreak of Human Monkeypox Virus. A Comprehensive Literature Review Study

Monkeypox was caused by Monkeypox Virus (MPXV) and can infect both humans and animals. An understanding of the interplay between host immunity and genetic diversity was necessary to understand the etiology and epidemiology of monkeypox disease. Objective: To clarify how genetic differences and host immune responses interact when a moneypox infection occurs. Furthermore, we also aim to provide insights into individual variability in illness outcomes and possible treatment targets by investigating how distinct genetic profiles affect immune system activation and efficacy. Methods: Recent research on monkeypox, concentrating on the immune response mechanisms of the host and genetic variables linked to virus vulnerability have thoroughly analyzed. For this purpose, the data were searched from various research engines such as google scholar, pubmed, medline etc., by using different key words i.e., monkeypox and host immunity, monkeypox and antibodies interactions, monkeypox outbreak, mnkeypox strains. Conclusions: The way a monkeypox infection progresses and turns out was greatly influenced by the interplay between host genetic differences and immunological responses. Public health initiatives and the creation of tailored treatment plans can both benefit from the identification of genetic markers linked to immunological response profiles and vulnerability.

국내 ESG 경영 우수기업의 지속가능경영보고서에 나타난 DEI 실천 분석

The purpose of this study was to identify the current status and characteristics of diversity, equity, and inclusion (DEI) activities implemented by companies in South Korea and to provide insights into future directions for development. To achieve this, the study analyzed the DEI-related activities of companies consistently rated as excellent in ESG management evaluations, based on their sustainability reports. Texts relevant to DEI from 86 sustainability reports for the year 2023, covering activities from January to December 2022, were collected and analyzed. The results revealed that, first, the term “D&I” is used more frequently than “DEI” in sustainability reports, and DEI is often presented in the context of human rights management. Second, within the Plan (input) - Do (execution) - See (output) framework, categories identified include in the Plan area: the establishment of DEI management principles, setting DEI promotion strategies, and constructing DEI governance; in the Do area: fostering a DEI organizational culture, DEI-based talent development, and DEI-based human resource management; and in the See (output) area: managing human diversity, board diversity, and DEI performance management. Based on the findings, both academic and practical implications were presented, along with suggestions for the future role of HRD in relation to DEI

Representation in best-selling preschool storybook apps in the United States

ABSTRACT In this study, we examine preschool storybook apps to identify the types of characters represented in these stories and how they relate to design quality and opportunities for children to build their vocabularies – a significant predictor of later success in learning to read. Specifically, we sought to understand (a) how storybook apps portray gender, race, and disability status; (b) how these characteristics compare in apps that contain the most and least opportunities to learn vocabulary; and (c) how these characteristics compare in apps with design features that might provide additional support for children’s word learning. To do so, we conducted a content analysis of 70 best-selling preschool storybook apps in the United States. Results indicate that most protagonists in these apps are animals, while human characters are overwhelmingly white, able-bodied, and male, particularly in apps with the highest percentage of advanced vocabulary and design qualities that are most likely to support children’s word learning. Thus, apps with the greatest learning potential lack human diversity, raising significant concerns for inclusive education.

Revisiting biochemical pathways for lead and cadmium tolerance by domain bacteria, eukarya, and their joint action in bioremediation.

With the advent rise is in urbanization and industrialization, heavy metals (HMs) such as lead (Pb) and cadmium (Cd) contamination have increased considerably. It is among the most recalcitrant pollutants majorly affecting the biotic and abiotic components of the ecosystem like human well-being, animals, soil health, crop productivity, and diversity of prokaryotes (bacteria) and eukaryotes (plants, fungi, and algae). At higher concentrations, these metals are toxic for their growth and pose a significant environmental threat, necessitating innovative and sustainable remediation strategies. Bacteria exhibit diverse mechanisms to cope with HM exposure, including biosorption, chelation, and efflux mechanism, while fungi contribute through mycorrhizal associations and hyphal networks. Algae, especially microalgae, demonstrate effective biosorption and bioaccumulation capacities. Plants, as phytoremediators, hyperaccumulate metals, providing a nature-based approach for soil reclamation. Integration of these biological agents in combination presents opportunities for enhanced remediation efficiency. This comprehensive review aims to provide insights into joint action of prokaryotic and eukaryotic interactions in the management of HM stress in the environment.

Upaya Pemerintah Dalam Mengelola Diversity Sumber Daya Manusia Di Kecamatan Gunungsitoli Barat

Kecamatan Gunungsitoli Barat is an area rich in cultural diversity, religion and strong customary traditions, and is inhabited by people with diverse ethnic backgrounds, including Batak and Malay. This diversity, although a great potential, also presents challenges for sub-district government organizations, especially in managing ethnic and cultural differences that can trigger social tensions. Issues of discrimination and unequal access to economic resources and employment opportunities are also issues that require serious attention. In addition, the limited political participation of some groups threatens the balance of representation in the sub-district government. This research uses a qualitative approach with a case study method to identify the challenges faced by the sub-district government in managing human resource diversity. The results show that appropriate strategies and policies are needed to create harmony in managing such diversity. Three main efforts that can be made by the sub-district government include: a) organizing cross-cultural training programs, b) implementing inclusive policies to ensure equal opportunities for all individuals, and c) building a monitoring and evaluation system to ensure effectiveness and transparency in managing HR diversity.

Abstract B012: Prioritization of ancestry-specific variations in disease data helps to alleviate bias in genomic data

Abstract 95% of sequencing data is from individuals of European descent. Underrepresentation of non- European individuals in genomic resources has limited our understanding of the effects of population-specific variants on complex traits and disease. Human populations have undergone selection for variants beneficial to survival in their environment, resulting in individuals with genetic variants unique to their ancestral populations. While these variants can impact disease occurrence and treatment outcome, genetic ancestry is often unaccounted for in disease modeling. Lack of ancestral population representation in data has led to disparate disease outcomes and treatment. While the primary proposed solution to this problem is more diverse sequencing of patients, these efforts will take years of effort and continual work to maintain the diversity balance. Additionally, they will not solve the issue; clinical trials cannot expect to capture human global diversity at every stage. Here we show we can mitigate data bias by utilizing readily available genomic population databases to target genes with ancestrally relevant variations. Our AI model, PhyloFrame, creates equitable gene signatures from transcriptomic input data. PhyloFrame corrects for ancestral bias in data by utilizing genomic population databases and functional interaction networks to identify genes both relevant to disease and associated with a variant unique to a single ancestry. PhyloFrame uses gnomAD data to quantify genome-wide ancestry-specific allele frequencies from a large cohort of healthy individuals, which PhyloFrame uses to create ancestry-agnostic signatures when modeling disease data. Our model demonstrates the utility of including readily available population-level data from healthy individuals in AI methods to overcome existing genomic data bias. PhyloFrame serves also as a demonstration of how equitable AI methods create gene signatures applicable across ancestries without requiring sample-specific ancestry information. Our model demonstrates how AI can be used to help mitigate ancestral bias in genomic data using preexisting data and contribute to equitable representation in medical research. Citation Format: Leslie A. Smith, Kiley Graim, James A. Cahill. Prioritization of ancestry-specific variations in disease data helps to alleviate bias in genomic data [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B012.

Abstract A007: Beyond continental ancestry categories: trans-population genomic similarity continuum reveals overlooked somatic-germline interactions across cancer types

Abstract A growing body of research highlighted a strong presence of continuums that describe human genomic diversity. Historical scholarship has also extensively investigated the use of discrete classification systems in human genomics further questioning their validity. To investigate the limiting effect of pre-defined stratification, we performed a wide comparative driver GWAS analysis at the trans-population (i.e. without stratification) vs continent-based population levels across 16 cancer types. Results demonstrate that in the MSK-IMPACT cohort (n = 56,826 samples), the analysis of the trans-population genomic similarity continuum captures significant somatic-germline interactions (p < 5x10-8) in cancer type-specific and pancancer cohorts, with a set of interactions overlooked by the discrete continent-based paradigm. We demonstrate that overlooked germline SNPs have similar allele frequencies and directional relationships with somatic alterations across pre-defined discrete categories, and that earlier stratification prevents their detection due to lowered statistical power. PheWAS analysis of detected germline variants revealed associations with cancer and non-cancer phenotypes reported in previous studies as well as novel hits. To expand the scope of the trans-population lens, we carried out a comparative analysis on 17 whole-exome TCGA cohorts to identify potential cancer drivers based on mutational frequencies. Results similarly revealed known and potential cancer drivers at the trans-population level that would be overlooked when pre-defined continent-based stratification is applied. The lens we adopt further highlights the necessity for new quantitative perspectives to comprehensively detect genomic patterns and to leverage entire genomic datasets without pre-defined stratification schemes. Citation Format: Hussein Mohsen, Tomin Perea-Chamblee, Jian Carrot-Zhang. Beyond continental ancestry categories: trans-population genomic similarity continuum reveals overlooked somatic-germline interactions across cancer types [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A007.

9,000 years of genetic continuity in southernmost Africa demonstrated at Oakhurst rockshelter

Southern Africa has one of the longest records of fossil hominins and harbours the largest human genetic diversity in the world. Yet, despite its relevance for human origins and spread around the globe, the formation and processes of its gene pool in the past are still largely unknown. Here, we present a time transect of genome-wide sequences from nine individuals recovered from a single site in South Africa, Oakhurst Rockshelter. Spanning the whole Holocene, the ancient DNA of these individuals allows us to reconstruct the demographic trajectories of the indigenous San population and their ancestors during the last 10,000 years. We show that, in contrast to most regions around the world, the population history of southernmost Africa was not characterized by several waves of migration, replacement and admixture but by long-lasting genetic continuity from the early Holocene to the end of the Later Stone Age. Although the advent of pastoralism and farming substantially transformed the gene pool in most parts of southern Africa after 1,300 bp, we demonstrate using allele-frequency and identity-by-descent segment-based methods that the ‡Khomani San and Karretjiemense from South Africa still show direct signs of relatedness to the Oakhurst hunter-gatherers, a pattern obscured by recent, extensive non-Southern African admixture. Yet, some southern San in South Africa still preserve this ancient, Pleistocene-derived genetic signature, extending the period of genetic continuity until today.

Universality versus Cultural relativism in International Human Rights: A Case Study of the Anti-Homosexuality Act of Uganda 2023

This research examines the frequent conflict that has emerged between the universal human rights standard and the indigenous cultural practices with special attention paid to the Anti-Homosexuality Act of Uganda of 2023. The Act criminalized same-sex relationships, an act that is in violation of universal human rights principles and showed a probable conflict between international norms and local cultural values. This review unravels how the Anti-Homosexuality Act of Uganda fits with or goes against international human rights commitments and further to determine more general implications of balancing universal principles against cultural relativism. The doctrinal approach adopted in this study includes a review of relevant international treaties, Uganda’s legislation and academic literature. The findings reveal that the Act, to an extent, undermines universal principles of human rights through the violation of rights to privacy, dignity, and equality. Such tug of war will require a lot of inclusive dialogue with the local communities and advocacy for protection of human rights which respects the cultural context. In addition, international organizations should support capacity building and facilitate debates that improve tolerance and respect for human rights. The work will engender a debate in reconciling universal human rights and cultural diversity, as well as emerging lessons for more effective and sensitive strategies in international human rights advocacy. Keywords: Universality, Cultural relativism, Human Rights and Homosexuality

Few-Human-Interaction Reinforcement Learning for Autonomous Transbronchial Intervention.

The transbronchial interventional surgery presents challenges with winding and convoluted pathways, prone to compression and friction. Current autonomous planning struggles to reach deeper bronchial positions, and hard to consider multiple conflicting goals simultaneously. This article introduces an innovative planning scheme with preference weights to achieve smooth, frictionless, and collision-free autonomous transbronchial intervention with continuum robot (CR). A few-human-interaction twin-delayed deep deterministic policy gradient (FHITD3) generated from surgeon preference guidance is proposed, which determines the optimal strategy for the motion of CR. Preference knowledge is generated through interaction between human and few diversity samples. An abstract actuator space description is proposed for the posture and position representation of CR during movement within bronchus. A contact motion analysis strategy is proposed to calculate real-time attitude of CR in contact with bronchus. In addition, an oscillation suppression approach to address CR's unsmooth distal end trajectory is proposed. Simulated experiments show that the CR autonomously completes intervention tasks with a smooth and stable trajectory, reducing distal end oscillation by over 45%. It achieves a target endpoint within the fourth level bronchus (approximately 5 mm diameter) with over 90% probability.

Challenging Misconceptions about Race in Undergraduate Genetics.

Racial biases, which harm marginalized and excluded communities, may be combatted by clarifying misconceptions about race during biology lessons. We developed a human genetics laboratory activity that challenges the misconception that race is biological (biological essentialism). We assessed the relationship between this activity and student outcomes using a survey of students' attitudes about biological essentialism and color-evasive ideology and a concept inventory about phylogeny and human diversity. Students in the human genetics laboratory activity showed a significant decrease in their acceptance of biological essentialism compared with a control group, but did not show changes in color-evasive ideology. Students in both groups exhibited increased knowledge in both areas of the concept inventory, but the gains were larger in the human genetics laboratory. In the second iteration of this activity, we found that only white students' decreases in biological essentialist beliefs were significant and the activity failed to decrease color-evasive ideologies for all students. Concept inventory gains were similar and significant for both white and non-white students in this iteration. Our findings underscore the effectiveness of addressing misconceptions about the biological origins of race and encourage more research on ways to effectively change damaging student attitudes about race in undergraduate genetics education.

Small populations of Palaeolithic humans in Cyprus hunted endemic megafauna to extinction.

The hypothesized main drivers of megafauna extinctions in the late Quaternary have wavered between over-exploitation by humans and environmental change, with recent investigations demonstrating more nuanced synergies between these drivers depending on taxon, spatial scale, and region. However, most studies still rely on comparing archaeologically based chronologies of timing of initial human arrival into naïve ecosystems and palaeontologically inferred dates of megafauna extinctions. Conclusions arising from comparing chronologies also depend on the reliability of dated evidence, dating uncertainties, and correcting for the low probability of preservation (Signor-Lipps effect). While some models have been developed to test the susceptibility of megafauna to theoretical offtake rates, none has explicitly linked human energetic needs, prey choice, and hunting efficiency to examine the plausibility of human-driven extinctions. Using the island of Cyprus in the terminal Pleistocene as an ideal test case because of its late human settlement (~14.2-13.2 ka), small area (~11 000 km2), and low megafauna diversity (2 species), we developed stochastic models of megafauna population dynamics, with offtake dictated by human energetic requirements, prey choice, and hunting-efficiency functions to test whether the human population at the end of the Pleistocene could have caused the extinction of dwarf hippopotamus (Phanourios minor) and dwarf elephants (Palaeoloxodon cypriotes). Our models reveal not only that the estimated human population sizes (n = 3000-7000) in Late Pleistocene Cyprus could have easily driven both species to extinction within < 1000 years, the model predictions match the observed, Signor-Lipps-corrected chronological sequence of megafauna extinctions inferred from the palaeontological record (P. minor at ~12-11.1 ka, followed by P. cypriotes at ~10.3-9.1 ka).

Evaluation of genotype imputation using Glimpse tools on low coverage ancient DNA.

Ancient DNA provides a unique frame for directly studying human population genetics in time and space. Still, since most of the ancient genomic data is low coverage, analysis is confronted with a low number of SNPs, genotype uncertainties, and reference-bias. Here, we for the first time benchmark the two distinct versions of Glimpse tools on 120 ancient human genomes from Eurasia including those largely from previously under-evaluated regions and compare the performance of genotype imputation with de facto analysis approaches for low coverage genomic data analysis. We further investigate the impact of two distinct reference panels on imputation accuracy for low coverage genomic data. We compute accuracy statistics and perform PCA and f4-statistics to explore the behaviour of genotype imputation on low coverage data regarding (i)two versions of Glimpse, (ii)two reference panels, (iii)four post-imputation filters and coverages, as well as (iv)data type and geographical origin of the samples on the analyses. Our results reveal that even for 0.1X coverage ancient human genomes, genotype imputation using Glimpse-v2 is suitable. Additionally, using the 1000 Genomes merged with Human Genome Diversity Panel improves the accuracy of imputation for the rare variants with low MAF, which might be important not only for ancient genomics but also for modern human genomic studies based on low coverage data and for haplotype-based analysis. Most importantly, we reveal that genotype imputation of low coverage ancient human genomes reduces the genetic affinity of the samples towards human reference genome. Through solving one of the most challenging biases in data analysis, so-called reference bias, genotype imputation using Glimpse v2 is promising for low coverage ancient human genomic data analysis and for rare-variant-based and haplotype-based analysis.

GGTyper: genotyping complex structural variants using short-read sequencing data.

Complex structural variants (SVs) are genomic rearrangements that involve multiple segments of DNA. They contribute to human diversity and have been shown to cause Mendelian disease. Nevertheless, our abilities to analyse complex SVs are very limited. As opposed to deletions and other canonical types of SVs, there are no established tools that have explicitly been designed for analysing complex SVs. Here, we describe a new computational approach that we specifically designed for genotyping complex SVs in short-read sequenced genomes. Given a variant description, our approach computes genotype-specific probability distributions for observing aligned read pairs with a wide range of properties. Subsequently, these distributions can be used to efficiently determine the most likely genotype for any set of aligned read pairs observed in a sequenced genome. In addition, we use these distributions to compute a genotyping difficulty for a given variant, which predicts the amount of data needed to achieve a reliable call. Careful evaluation confirms that our approach outperforms other genotypers by making reliable genotype predictions across both simulated and real data. On up to 7829 human genomes, we achieve high concordance with population-genetic assumptions and expected inheritance patterns. On simulated data, we show that precision correlates well with our prediction of genotyping difficulty. This together with low memory and time requirements makes our approach well-suited for application in biomedical studies involving small to very large numbers of short-read sequenced genomes. Source code is available at https://github.com/kehrlab/Complex-SV-Genotyping.

The Ethics of Artificial Intelligence and Autonomous Systems: Review

Artificial intelligence (AI) and autonomous systems are rapidly advancing technologies that offer significant benefits but also pose new ethical challenges. This review aims to comprehensively analyze the key ethical issues related to AI and autonomy through an expanded discussion of relevant literature. The development of advanced AI and autonomous systems could enable unprecedented capabilities but also risks that are unprecedented in their nature and scale. Ensuring these technologies are developed and applied in an ethical manner will require addressing issues around safety, transparency, accountability, and the prioritization of human values. Researchers have proposed technical and philosophical approaches to building "friendly" or "beneficial" AI that avoids potential harms. However, many open questions remain about how to properly specify and validate ethical constraints for systems that may surpass human levels of intelligence. Autonomous systems like self-driving vehicles also introduce new ethical dilemmas around responsibility and decision- making in safety-critical situations. Standards are needed to help guide the design of autonomous functions to be transparent, predictable, and respectful of human dignity and diversity. Governments and international organizations have begun outlining policy recommendations for developing AI that is trustworthy and compatible with human rights, privacy, and democratic values.