Lawrence Hunter

Tiffany J. Callahan, Ignacio J. Tripodi, Adrianne L. Stefanski et al. · berkeley, harvard

Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data, but researchers face significant integration challenges. Knowledge graphs (KGs) are used to model complex phenomena, and methods exist to construct them automatically. However, tackling complex biomedical integration problems requires flexibility in the way knowledge is modeled. Moreover, existing KG construction methods provide robust tooling at the cost of fixed or limited choices among knowledge representation models. PheKnowLator (Phenotype Knowledge Translator) is a semantic ecosystem for automating the FAIR (Findable, Accessible, Interoperable, and Reusable) construction of ontologically grounded KGs with fully customizable knowledge representation. The ecosystem includes KG construction resources (e.g., data preparation APIs), analysis tools (e.g., SPARQL endpoints and abstraction algorithms), and benchmarks (e.g., prebuilt KGs and embeddings). We evaluated the ecosystem by systematically comparing it to existing open-source KG construction methods and by analyzing its computational performance when used to construct 12 large-scale KGs. With flexible knowledge representation, PheKnowLator enables fully customizable KGs without compromising performance or usability.

Hector Zenil, Jesper Tegnér, Felipe S. Abrahão et al. · cambridge

Recent advances in machine learning and AI, including Generative AI and LLMs, are disrupting technological innovation, product development, and society as a whole. AI's contribution to technology can come from multiple approaches that require access to large training data sets and clear performance evaluation criteria, ranging from pattern recognition and classification to generative models. Yet, AI has contributed less to fundamental science in part because large data sets of high-quality data for scientific practice and model discovery are more difficult to access. Generative AI, in general, and Large Language Models in particular, may represent an opportunity to augment and accelerate the scientific discovery of fundamental deep science with quantitative models. Here we explore and investigate aspects of an AI-driven, automated, closed-loop approach to scientific discovery, including self-driven hypothesis generation and open-ended autonomous exploration of the hypothesis space. Integrating AI-driven automation into the practice of science would mitigate current problems, including the replication of findings, systematic production of data, and ultimately democratisation of the scientific process. Realising these possibilities requires a vision for augmented AI coupled with a diversity of AI approaches able to deal with fundamental aspects of causality analysis and model discovery while enabling unbiased search across the space of putative explanations. These advances hold the promise to unleash AI's potential for searching and discovering the fundamental structure of our world beyond what human scientists have been able to achieve. Such a vision would push the boundaries of new fundamental science rather than automatize current workflows and instead open doors for technological innovation to tackle some of the greatest challenges facing humanity today.

Tiffany J. Callahan, Adrianne L. Stefanski, Jin-Dong Kim et al.

Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Currently, the only definitive treatment of preeclampsia is delivery of the placenta, which is central to the pathogenesis of the disease. Transcriptional profiling of human placenta from pregnancies complicated by preeclampsia has been extensively performed to identify differentially expressed genes (DEGs). The decisions to investigate DEGs experimentally are biased by many factors, causing many DEGs to remain uninvestigated. A set of DEGs which are associated with a disease experimentally, but which have no known association to the disease in the literature are known as the ignorome. Preeclampsia has an extensive body of scientific literature, a large pool of DEG data, and only one definitive treatment. Tools facilitating knowledge-based analyses, which are capable of combining disparate data from many sources in order to suggest underlying mechanisms of action, may be a valuable resource to support discovery and improve our understanding of this disease. In this work we demonstrate how a biomedical knowledge graph (KG) can be used to identify novel preeclampsia molecular mechanisms. Existing open source biomedical resources and publicly available high-throughput transcriptional profiling data were used to identify and annotate the function of currently uninvestigated preeclampsia-associated DEGs. Experimentally investigated genes associated with preeclampsia were identified from PubMed abstracts using text-mining methodologies. The relative complement of the text-mined- and meta-analysis-derived lists were identified as the uninvestigated preeclampsia-associated DEGs (n=445), i.e., the preeclampsia ignorome. Using the KG to investigate relevant DEGs revealed 53 novel clinically relevant and biologically actionable mechanistic associations.

Tiffany J. Callahan, Adrianne L. Stefanski, Jordan M. Wyrwa et al.

Background: Common data models solve many challenges of standardizing electronic health record (EHR) data, but are unable to semantically integrate all the resources needed for deep phenotyping. Open Biological and Biomedical Ontology (OBO) Foundry ontologies provide computable representations of biological knowledge and enable the integration of heterogeneous data. However, mapping EHR data to OBO ontologies requires significant manual curation and domain expertise. Objective: We introduce OMOP2OBO, an algorithm for mapping Observational Medical Outcomes Partnership (OMOP) vocabularies to OBO ontologies. Results: Using OMOP2OBO, we produced mappings for 92,367 conditions, 8611 drug ingredients, and 10,673 measurement results, which covered 68-99% of concepts used in clinical practice when examined across 24 hospitals. When used to phenotype rare disease patients, the mappings helped systematically identify undiagnosed patients who might benefit from genetic testing. Conclusions: By aligning OMOP vocabularies to OBO ontologies our algorithm presents new opportunities to advance EHR-based deep phenotyping.

Sagi Shaier, Lawrence Hunter, Katharina Kann

Many dialogue systems (DSs) lack characteristics humans have, such as emotion perception, factuality, and informativeness. Enhancing DSs with knowledge alleviates this problem, but, as many ways of doing so exist, keeping track of all proposed methods is difficult. Here, we present the first survey of knowledge-enhanced DSs. We define three categories of systems - internal, external, and hybrid - based on the knowledge they use. We survey the motivation for enhancing DSs with knowledge, used datasets, and methods for knowledge search, knowledge encoding, and knowledge incorporation. Finally, we propose how to improve existing systems based on theories from linguistics and cognitive science.

Sagi Shaier, Lawrence E. Hunter, Katharina von der Wense

Both standalone language models (LMs) as well as LMs within downstream-task systems have been shown to generate statements which are factually untrue. This problem is especially severe for low-resource languages, where training data is scarce and of worse quality than for high-resource languages. In this opinion piece, we argue that LMs in their current state will never be fully trustworthy in critical settings and suggest a possible novel strategy to handle this issue: by building LMs such that can cite their sources - i.e., point a user to the parts of their training data that back up their outputs. We first discuss which current NLP tasks would or would not benefit from such models. We then highlight the expected benefits such models would bring, e.g., quick verifiability of statements. We end by outlining the individual tasks that would need to be solved on the way to developing LMs with the ability to cite. We hope to start a discussion about the field's current approach to building LMs, especially for low-resource languages, and the role of the training data in explaining model generations.

Sagi Shaier, Kevin Bennett, Lawrence Hunter et al.

State-of-the-art question answering (QA) models exhibit a variety of social biases (e.g., with respect to sex or race), generally explained by similar issues in their training data. However, what has been overlooked so far is that in the critical domain of biomedicine, any unjustified change in model output due to patient demographics is problematic: it results in the unfair treatment of patients. Selecting only questions on biomedical topics whose answers do not depend on ethnicity, sex, or sexual orientation, we ask the following research questions: (RQ1) Do the answers of QA models change when being provided with irrelevant demographic information? (RQ2) Does the answer of RQ1 differ between knowledge graph (KG)-grounded and text-based QA systems? We find that irrelevant demographic information change up to 15% of the answers of a KG-grounded system and up to 23% of the answers of a text-based system, including changes that affect accuracy. We conclude that unjustified answer changes caused by patient demographics are a frequent phenomenon, which raises fairness concerns and should be paid more attention to.

Sagi Shaier, Kevin Bennett, Lawrence E Hunter et al.

The differences between cloze-task language model (LM) probing with 1) expert-made templates and 2) naturally-occurring text have often been overlooked. Here, we evaluate 16 different LMs on 10 probing English datasets -- 4 template-based and 6 template-free -- in general and biomedical domains to answer the following research questions: (RQ1) Do model rankings differ between the two approaches? (RQ2) Do models' absolute scores differ between the two approaches? (RQ3) Do the answers to RQ1 and RQ2 differ between general and domain-specific models? Our findings are: 1) Template-free and template-based approaches often rank models differently, except for the top domain-specific models. 2) Scores decrease by up to 42% Acc@1 when comparing parallel template-free and template-based prompts. 3) Perplexity is negatively correlated with accuracy in the template-free approach, but, counter-intuitively, they are positively correlated for template-based probing. 4) Models tend to predict the same answers frequently across prompts for template-based probing, which is less common when employing template-free techniques.

Sagi Shaier, Lawrence E Hunter, Katharina von der Wense

Prior work has uncovered a set of common problems in state-of-the-art context-based question answering (QA) systems: a lack of attention to the context when the latter conflicts with a model's parametric knowledge, little robustness to noise, and a lack of consistency with their answers. However, most prior work focus on one or two of those problems in isolation, which makes it difficult to see trends across them. We aim to close this gap, by first outlining a set of -- previously discussed as well as novel -- desiderata for QA models. We then survey relevant analysis and methods papers to provide an overview of the state of the field. The second part of our work presents experiments where we evaluate 15 QA systems on 5 datasets according to all desiderata at once. We find many novel trends, including (1) systems that are less susceptible to noise are not necessarily more consistent with their answers when given irrelevant context; (2) most systems that are more susceptible to noise are more likely to correctly answer according to a context that conflicts with their parametric knowledge; and (3) the combination of conflicting knowledge and noise can reduce system performance by up to 96%. As such, our desiderata help increase our understanding of how these models work and reveal potential avenues for improvements.

George Arthur Baker, Ankush Raut, Sagi Shaier et al.

Previous work finds that recent long-context language models fail to make equal use of information in the middle of their inputs, preferring pieces of information located at the tail ends which creates an undue bias in situations where we would like models to be equally capable of using different parts of the input. Thus far, the problem has mainly only been considered in settings with single pieces of critical information, leading us to question what happens when multiple necessary pieces of information are spread out over the inputs. Here, we demonstrate the effects of the "lost in the middle" problem in the multi-hop question answering setting -- in which multiple reasoning "hops" over disconnected documents are required -- and show that performance degrades not only with respect to the distance of information from the edges of the context, but also between pieces of information. Additionally, we experiment with means of alleviating the problem by reducing superfluous document contents through knowledge graph triple extraction and summarization, and prompting models to reason more thoroughly using chain-of-thought prompting.

Sagi Shaier, George Arthur Baker, Chiranthan Sridhar et al.

Language models (LMs) have excelled in various broad domains. However, to ensure their safe and effective integration into real-world educational settings, they must demonstrate proficiency in specific, granular areas of knowledge. Existing cloze-style benchmarks, commonly used to evaluate LMs' knowledge, have three major limitations. They: 1) do not cover the educational domain; 2) typically focus on low-complexity, generic knowledge or broad domains, which do not adequately assess the models' knowledge in specific subjects; and 3) often rely on templates that can bias model predictions. Here, we introduce MALAMUTE, a multilingual, template-free, and highly granular probing dataset comprising expert-written, peer-reviewed probes from 71 university-level textbooks across three languages (English, Spanish, and Polish). MALAMUTE is the first education-based cloze-style dataset. It covers eight domains, each with up to 14 subdomains, further broken down into concepts and concept-based prompts, totaling 33,361 university curriculum concepts and 116,887 prompts. MALAMUTE's fine granularity, educational focus, and inclusion of both sentence-level and paragraph-level prompts make it an ideal tool for evaluating LMs' course-related knowledge. Our evaluation of masked and causal LMs on MALAMUTE shows that despite overall proficiency, they have significant gaps in knowledge when examined closely on specific subjects, hindering their safe use in classrooms and underscoring the need for further development.

Sagi Shaier, Lawrence E Hunter, Katharina von der Wense

Natural language processing has seen rapid progress over the past decade. Due to the speed of developments, some practices get established without proper evaluation. Considering one such case and focusing on reading comprehension, we ask our first research question: 1) How does the order of inputs -- i.e., question and context -- affect model performance? Additionally, given recent advancements in input emphasis, we ask a second research question: 2) Does emphasizing either the question, the context, or both enhance performance? Experimenting with 9 large language models across 3 datasets, we find that presenting the context before the question improves model performance, with an accuracy increase of up to $31\%$. Furthermore, emphasizing the context yields superior results compared to question emphasis, and in general, emphasizing parts of the input is particularly effective for addressing questions that models lack the parametric knowledge to answer. Experimenting with both prompt-based and attention-based emphasis methods, we additionally find that the best method is surprisingly simple: it only requires concatenating a few tokens to the input and results in an accuracy improvement of up to $36\%$, allowing smaller models to outperform their significantly larger counterparts.

Tiffany J. Callahan, Harrison Pielke-Lombardo, Ignacio J. Tripodi et al.

Knowledge-based biomedical data science (KBDS) involves the design and implementation of computer systems that act as if they knew about biomedicine. Such systems depend on formally represented knowledge in computer systems, often in the form of knowledge graphs. Here we survey the progress in the last year in systems that use formally represented knowledge to address data science problems in both clinical and biological domains, as well as on approaches for creating knowledge graphs. Major themes include the relationships between knowledge graphs and machine learning, the use of natural language processing, and the expansion of knowledge-based approaches to novel domains, such as Chinese Traditional Medicine and biodiversity.