Artificial Intelligence in Oncology Drug Discovery and Development

There exists a profound conflict at the heart of oncology drug development. The efficiency of the drug development process is falling, leading to higher costs per approved drug, at the same time personalised medicine is limiting the target market of each new medicine. Even as the global economic burden of cancer increases, the current paradigm in drug development is unsustainable. In this book, we discuss the development of techniques in machine learning for improving the efficiency of oncology drug development and delivering cost-effective precision treatment. We consider how to structure data for drug repurposing and target identification, how to improve clinical trials and how patients may view artificial intelligence

Characterization of chemical and bioactive properties of the grain of new inbred maize lines

The objective of this study was to early identify genotypes with increased potential for the development of hybrids with high nutritional and functional value, suitable for food production, by assessing the grain quality parameters of eleven new maize inbred lines. The inbreds, including nine standard yellow and two red kernel lines, were grown in the experimental field of the Maize Research Institute at the location of Zemun Polje, Serbia in 2020. Wholegrain maize flour was obtained by a dry grind process on a laboratory mill. The assessment of the chemical composition and content of certain bioactive compounds, as well as total antioxidant capacity, was conducted using standard laboratory procedures. The highest starch content (73.73%), was determined in Line 8, while Line 10 had the highest protein content (12.82%). The lowest oil content was determined in red kernel Line 7, namely 4.87%. Among soluble proteins, the α-zein fraction was dominant in most of the lines, ranging from 0.92% to 3.57%. The glutelin and albumin fraction were present in a lower percentage, followed by the globulin fraction. The highest content of total fibers (NDF) was determined in red kernel Line 9 (15.77%). Line 8 was the richest in total carotenoids (21.08 μg βCE/g d.m.), while Line 7 had the highest total antioxidant capacity (34.30 mmol Trolox/kg d.m.), which can be explained by the presence of anthocyanins in the red grain. Line 1 had the highest content of total sugars (3.36%), and Line 4 had the lowest (1.44%). All samples of new inbred lines investigated in this study showed good quality parameters regarding chemical composition and bioactive properties. The obtained results may provide some valuable guidelines needed in the following stages of maize breeding as well as open up various possibilities for the utilization of wholegrain maize flour in the food industry

Research and Creative Activity, July 1, 2019-June 30, 2020: Major Sponsored Programs and Faculty Accomplishments in Research and Creative Activity, University of Nebraska-Lincoln

Foreword by Bob Wilhelm, Vice Chancellor for Research and Economic Development: This booklet highlights successes in research, scholarship and creative activity by University of Nebraska–Lincoln faculty during the fiscal year running July 1, 2019, to June 30, 2020. It lists investigators, project titles and funding sources on major grants and sponsored awards received during the year; fellowships and other recognitions and honors bestowed on our faculty; books published by faculty; performances, exhibitions and other creative activity; and patents and licensing agreements issued. Based on your feedback, the Office of Research and Economic Development expanded this publication to include peer-reviewed journal articles and conference presentations and recognize students and faculty mentors participating in the Undergraduate Creative Activities and Research Experience Program (UCARE) and the First-Year Research Experiences program (FYRE). While metrics cannot convey the full story of our work, they are tangible measures of impact. Nebraska achieved a record $317 million in total research expenditures in FY 2019, a 26$450 million in research expenditures by 2025. Husker researchers are stimulating economic growth through university-sponsored industry activity. Nebraska Innovation Campus created 1,657 jobs statewide and had a total economic impact of $324.1 million in FY 2019. NUtech Ventures brought in$6.6 million in licensing income in FY 2020. The University of Nebraska system now ranks 65th among the top 100 academic institutions receiving U.S. patents, jumping 14 spots from 2019. I am proud of the Nebraska Research community for facing the challenges of 2020 with grit and determination. Our researchers quickly adapted to develop solutions for an evolving pandemic — all while working apart and keeping themselves and their families safe. As an institution, we made a commitment to embrace an anti-racism journey and work toward racial equity. Advancing conversations and developing lasting solutions is among the most important work we can do as scholars. Against the backdrop of the pandemic, rising racial and social tensions, and natural disasters, Nebraska researchers worked diligently to address other pressing issues, such as obesity and related diseases, nanomaterials, agricultural resilience and the state’s STEM workforce. Let’s continue looking forward to what we can accomplish together. Thank you for participating in the grand challenges process and helping identify the wicked problems that Nebraska has unique expertise to solve. Soon, ORED will unveil a Research Roadmap that outlines how our campus will develop research expertise; enrich creative activity; bolster commitment to diversity, equity and inclusion; enhance economic development; and much more. Amidst the uncertainty of 2020, I remain confident in our faculty’s talent and commitment. I am pleased to present this record of accomplishments. Contents Awards of $5 Million or More Awards of$1 Million to $4,999,999 Awards of$250,000 to $999,999 Early Career Awards Arts and Humanities Awards of$250,000 or More Arts and Humanities Awards of $50,000 to$249,999 Arts and Humanities Awards of $5,000 to$49,999 Patents License Agreements Creative Activity Books Recognitions and Honors Journal Articles Conference Presentations UCARE and FYRE Projects Glossar

Pacific Symposium on Biocomputing 2023

The Pacific Symposium on Biocomputing (PSB) 2023 is an international, multidisciplinary conference for the presentation and discussion of current research in the theory and application of computational methods in problems of biological significance. Presentations are rigorously peer reviewed and are published in an archival proceedings volume. PSB 2023 will be held on January 3-7, 2023 in Kohala Coast, Hawaii. Tutorials and workshops will be offered prior to the start of the conference.PSB 2023 will bring together top researchers from the US, the Asian Pacific nations, and around the world to exchange research results and address open issues in all aspects of computational biology. It is a forum for the presentation of work in databases, algorithms, interfaces, visualization, modeling, and other computational methods, as applied to biological problems, with emphasis on applications in data-rich areas of molecular biology.The PSB has been designed to be responsive to the need for critical mass in sub-disciplines within biocomputing. For that reason, it is the only meeting whose sessions are defined dynamically each year in response to specific proposals. PSB sessions are organized by leaders of research in biocomputing's 'hot topics.' In this way, the meeting provides an early forum for serious examination of emerging methods and approaches in this rapidly changing field

Genome-wide analyses to investigate the genetic factors underlying specific psychotic experiences in adolescence and their overlap with psychiatric disorders

Psychotic experiences (PEs) are non-clinical traits, which at the extreme resemble symptoms of psychotic disorders, such as schizophrenia. PEs during adolescence have been associated with a range of psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. Adolescent PEs are moderately heritable, however no genetic variant has been associated with adolescent PEs at genome-wide significance. There are limited and mixed findings regarding a common genetic overlap between adolescent PEs and psychiatric disorders. Following a systematic review of previous studies using genome-wide genetic data to investigate adolescent PEs, this thesis sets out to improve upon previous research through two main approaches: 1) the use of specific and quantitative measures of adolescent PEs, and 2) the combined analysis of multiple samples. In Chapter 2, a GWAS (genome-wide association study) is performed using specific and quantitative measures of adolescent PEs using the TEDS (Twins Early Development Study) sample. In Chapter 3, the procedure in which phenotypic data is normalised and controlled for covariates is investigated. The remainder of the thesis is based on the combined analysis of three European adolescent samples (TEDS and two others) with available PE data. In Chapter 4, the phenotypic data relating to PEs within each sample are harmonised to create four measures assessing specific PE traits that are comparable across samples. These four traits are Paranoia and Hallucinations, Cognitive Disorganisation, Anhedonia, and Parent-rated Negative Symptoms. In Chapter 5, mega-GWASs of the four specific PE traits (N = 6,297-10,098) are performed across the three samples to highlight associated genetic variation. Chapter 6 then estimates the variance in specific PEs, and the covariance between PEs, that is attributable to common genetic variation. Chapter 4 7 uses both polygenic risk scoring and LD-score regression to test for common genetic overlap between specific adolescent PEs and schizophrenia, bipolar disorder, and major depression. This thesis provides evidence that specific PEs during adolescence show common genetic effects, and have a common genetic overlap with psychiatric disorders, specifically schizophrenia and major depression. The findings of this thesis are placed in the context of previous research, with a discussion of the limitations and future direction

Generation and Applications of Knowledge Graphs in Systems and Networks Biology

The acceleration in the generation of data in the biomedical domain has necessitated the use of computational approaches to assist in its interpretation. However, these approaches rely on the availability of high quality, structured, formalized biomedical knowledge. This thesis has the two goals to improve methods for curation and semantic data integration to generate high granularity biological knowledge graphs and to develop novel methods for using prior biological knowledge to propose new biological hypotheses. The first two publications describe an ecosystem for handling biological knowledge graphs encoded in the Biological Expression Language throughout the stages of curation, visualization, and analysis. Further, the second two publications describe the reproducible acquisition and integration of high-granularity knowledge with low contextual specificity from structured biological data sources on a massive scale and support the semi-automated curation of new content at high speed and precision. After building the ecosystem and acquiring content, the last three publications in this thesis demonstrate three different applications of biological knowledge graphs in modeling and simulation. The first demonstrates the use of agent-based modeling for simulation of neurodegenerative disease biomarker trajectories using biological knowledge graphs as priors. The second applies network representation learning to prioritize nodes in biological knowledge graphs based on corresponding experimental measurements to identify novel targets. Finally, the third uses biological knowledge graphs and develops algorithmics to deconvolute the mechanism of action of drugs, that could also serve to identify drug repositioning candidates. Ultimately, the this thesis lays the groundwork for production-level applications of drug repositioning algorithms and other knowledge-driven approaches to analyzing biomedical experiments

Research and Creative Activity, July 01, 2021-June 30, 2022: Major Sponsored Programs and Faculty Accomplishments in Research and Creative Activity, University of Nebraska-Lincoln

Foreword by Bob Wilhelm, Vice Chancellor for Research and Economic Development: This booklet highlights successes in research, scholarship and creative activity by University of Nebraska–Lincoln faculty during the fiscal year running July 1, 2021, to June 30, 2022. It lists investigators, project titles and funding sources on major grants and sponsored awards that were active during the year; fellowships and other recognitions and honors bestowed on our faculty; books, chapters and creative literature published by faculty; performances, exhibitions and other examples of creative activity; patents and licensing agreements; and conference presentations. In recognition of the important role faculty play in the undergraduate experience at Nebraska, this booklet notes the students and mentors participating in the Undergraduate Creative Activities and Research Experience (UCARE) and the First-Year Research Experience (FYRE) programs. Increasing impact through research and creative activity is one of the six core aims of the N2025 strategic plan. A few measurements of progress made this year: • UNL achieved a record $321 million in total research expenditures in FY 2021, a 31• Our faculty earned 1,560 sponsored research awards in FY 2021. N2025 aims also include contributing to economic growth throughout the state and broadening Nebraska’s engagement in community, industry and global partnerships. These are some measures of our efforts to commercialize university-sponsored research and partner with industry: • Nebraska Innovation Campus created 2,127 jobs statewide. The cumulative impact of NIC investments totals$328.9 million. • Industry sponsorship supported $19.8 million in research expenditures. • NUtech Ventures brought in$6.36 million in licensing income. I want to thank the Nebraska Research community for its willingness to collaborate, mentor and redefine success in research and creative activity. Your leadership is paving the way for future growth and providing an unparalleled educational experience. At Nebraska, it is the people who make the place. Because of your dedication and expertise, Nebraska is positioned to solve some of the world’s most wicked problems. I am impressed by your commitment to the Grand Challenges initiative, a strategic investment of up to $40 million over four years for projects in the high-impact areas of anti-racism and racial equity; climate resilience; early childhood education and development; health equity; quantum science and engineering; science and technology literacy for society; and sustainable food and water security. More than 180 faculty, staff and students are contributing to projects funded in Year 1. Another N2025 aim is to create a climate that emphasizes, prioritizes and expands inclusive excellence and diversity. In the Office of Research and Economic Development, we continue to seek ways to remove barriers to success and ensure all Nebraska researchers have the resources they need to thrive. Thank you for the feedback you’ve thoughtfully provided. I am pleased to present this record of accomplishments. Contents Awards of$5 Million or More Awards of $1 Million to$4,999,999 Awards of $250,000 to$999,999 Early Career Awards Arts and Humanities Awards of $250,000 or More Arts and Humanities Awards of$50,000 to $249,999 Arts and Humanities Awards of$5,000 to $49,999 Patents License Agreements National Science Foundation Innovation Corps Teams Creative Activity Books Recognitions and Honors Journal Articles Conference Presentations UCARE and FYRE Projects Glossar

Genome-wide analyses to investigate the genetic factors underlying specific psychotic experiences in adolescence and their overlap with psychiatric disorders

Psychotic experiences (PEs) are non-clinical traits, which at the extreme resemble symptoms of psychotic disorders, such as schizophrenia. PEs during adolescence have been associated with a range of psychiatric disorders, including schizophrenia, bipolar disorder, and major depression. Adolescent PEs are moderately heritable, however no genetic variant has been associated with adolescent PEs at genome-wide significance. There are limited and mixed findings regarding a common genetic overlap between adolescent PEs and psychiatric disorders. Following a systematic review of previous studies using genome-wide genetic data to investigate adolescent PEs, this thesis sets out to improve upon previous research through two main approaches: 1) the use of specific and quantitative measures of adolescent PEs, and 2) the combined analysis of multiple samples. In Chapter 2, a GWAS (genome-wide association study) is performed using specific and quantitative measures of adolescent PEs using the TEDS (Twins Early Development Study) sample. In Chapter 3, the procedure in which phenotypic data is normalised and controlled for covariates is investigated. The remainder of the thesis is based on the combined analysis of three European adolescent samples (TEDS and two others) with available PE data. In Chapter 4, the phenotypic data relating to PEs within each sample are harmonised to create four measures assessing specific PE traits that are comparable across samples. These four traits are Paranoia and Hallucinations, Cognitive Disorganisation, Anhedonia, and Parent-rated Negative Symptoms. In Chapter 5, mega-GWASs of the four specific PE traits (N = 6,297-10,098) are performed across the three samples to highlight associated genetic variation. Chapter 6 then estimates the variance in specific PEs, and the covariance between PEs, that is attributable to common genetic variation. Chapter 4 7 uses both polygenic risk scoring and LD-score regression to test for common genetic overlap between specific adolescent PEs and schizophrenia, bipolar disorder, and major depression. This thesis provides evidence that specific PEs during adolescence show common genetic effects, and have a common genetic overlap with psychiatric disorders, specifically schizophrenia and major depression. The findings of this thesis are placed in the context of previous research, with a discussion of the limitations and future direction