Biology subjects

Crawford, D. C.

Publications and source records attributed to Crawford, D. C..

3 recordsLinked to original sources

bioRxiv2026

PREP-aring is worth it: Success of the Case Western Reserve University Post-baccalaureate Research Education Program and its Scholars

The Post-baccalaureate Research Education Program (PREP), established by the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health in 2000, was a research-intense, one-year training program for recent college graduates from backgrounds uncommon in science who intended to matriculate with a PhD or MD/PhD program in preparation for an eventual career in biomedical research. Case Western Reserve University had an NIGMS-supported PREP (CasePREP) from 2007 to 2025, the year NIGMS terminated the PREP funding mechanism. A major goal of CasePREP was to prepare post-baccalaureate trainees (termed Scholars) for graduate school, and major metrics of success were measured as Scholars who a) matriculated in and b) completed PhD or MD/PhD programs. A major goal of NIGMS-supported PREPs was the retention of these scientists in the biomedical research workforce. We report here the extent that CasePREP met program goals as well as the economic and scientific impact NIGMS-supported PREP has had for a variety of stakeholders. Data from 18 CasePREP cohorts included self-reported (surveys, interviews, questionnaires) and public data (websites, PubMed, NIH Reporter). Descriptive statistics and large language models were used to describe the major outcomes related to program goals and a new resilience course as well as Scholar productivity and contribution to science. Between 2007 and 2025, CasePREP was awarded $5.6 million USD and trained 108 Scholars. Most (89%) Scholars resided outside of Ohio prior to the start of CasePREP, with 38.89% from Puerto Rico. Almost all (98%) Scholars completed the one-year program in Cleveland, Ohio, and of those, 83% entered a PhD or MD/PhD program. As of September 2025, 46 Scholars have completed a PhD program, two Scholars have completed an MD/PhD program, and 27 are still in training. The attrition rate for CasePREP Scholars in graduate school is currently 14.77%, much lower than the attrition rates of national PhD programs. Most CasePREP Scholars (69.44%) are co-authors on one or more published manuscripts, and these 406 published works have garnered 14,261 total citations, with an average 35.04 citations per publication. Termination of PREP represents a five-year loss of [~]$2.7 million USD to CasePREP, a budget that would have trained an additional 30 Scholars. CasePREP was a great success as measured by its major outcomes. CasePREP Scholars have persisted in science and have made substantial contributions to the scientific workforce and enterprise. PREPs in general provided a crucial bridge for research talents who had little prior research opportunities to realize their potential and career goals. NIGMS termination of PREP support has negative economic consequences and endangers an important pathway to a career in science for Americans who would not otherwise have similar opportunities.

scientific communication and education↗

bioRxiv2022

Omnigenic epistasis regulates complex trait heritability

A better understanding of genetic architecture will help translate genetic data into improved precision-based medicine and clinical care. Towards this end, we explored the use of sex-stratified analyses for several traits in the Hybrid Mouse Diversity Panel (HMDP) and UK Biobank to better determine trait polygenicity and identify contributing loci. This was accomplished by comparing the direction of allelic effects in males and females in sex-stratified analyses under the hypothesis that loci that are not associated with a trait should have equal chances of trending in the same direction of effect. Instead, we found that even for most alleles that do not meet nominal levels of statistical significance, the direction of effect in the two sexes was highly concordant. Results were consistent with hundreds of loci regulating each mouse trait and thousands of loci regulating each human trait, including traits for which no statistically significant loci were identified using conventional approaches. We also found evidence of likely spurious widespread epistasis. Collectively, these findings demonstrate the importance of stratifying by sex to discover novel associating loci, suggest a new method for identifying biologically rather than statistically significant associations, and caution that widespread marginal effects can lead to phantom epistasis.

genetics↗

bioRxiv2021

An Association Test of the Spatial Distribution of Rare Missense Variants within Protein Structures Improves Statistical Power of Sequencing Studies

Over 90% of variants are rare, and 50% of them are singletons in the Alzheimers Disease Sequencing Project Whole Exome Sequencing (ADSP WES) data. However, either single variant tests or unit-based tests are limited in the statistical power to detect the association between rare variants and phenotypes. To best utilize rare variants and investigate their biological effect, we exam their association with phenotypes in the context of protein. We developed a protein structure-based approach, POKEMON (Protein Optimized Kernel Evaluation of Missense Nucleotides), which evaluates rare missense variants based on their spatial distribution on the protein rather than allele frequency. The hypothesis behind this is that the three-dimensional spatial distribution of variants within a protein structure provides functional context and improves the power of association tests. POKEMON identified four candidate genes from the ADSP WES data, namely two known Alzheimers disease (AD) genes (TREM2 and SORL) and two novel genes (DUSP18 and CSF1R). For known AD genes, the signal from the spatial cluster is stable even if we exclude known AD risk variants, indicating the presence of additional low frequency risk variants within these genes. DUSP18 has a cluster of variants primarily shared by case subjects around the ligand-binding domain, and this cluster is further validated in a replication dataset with a larger sample size. POKEMON is an open-source tool available at https://github.com/bushlab-genomics/POKEMON.

bioinformatics↗