Craig Smail
A5080231471- Genomics and Rare Diseases
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Genomic variations and chromosomal abnormalities
- Genomics and Phylogenetic Studies
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
- Health Sciences Research and Education
- Genetic factors in colorectal cancer
- Pregnancy and preeclampsia studies
- Eosinophilic Esophagitis
- Vaccine Coverage and Hesitancy
- CRISPR and Genetic Engineering
- IL-33, ST2, and ILC Pathways
- Cancer-related molecular mechanisms research
- Primary Care and Health Outcomes
- Epigenetics and DNA Methylation
- Disaster Response and Management
- Clinical Laboratory Practices and Quality Control
- Health Policy Implementation Science
- Machine Learning in Healthcare
- Pharmaceutical Practices and Patient Outcomes
- Mental Health and Patient Involvement
- Genetics and Neurodevelopmental Disorders
Children's Mercy Hospital
2021-2024
University of Missouri–Kansas City
2021-2024
Mercy Research
2020-2024
Stanford University
2018-2022
Pacific Biosciences (United States)
2021
American Academy of Family Physicians
2014-2020
Children's Hospital of Philadelphia
2018
University of North Carolina at Chapel Hill
2018
Brigham and Women's Hospital
2018
Linde (United States)
2018
Outliers in the human transcriptome reveal functional effects of rare genetic variants.
Abstract Structural variants (SVs) and short tandem repeats (STRs) comprise a broad group of diverse DNA which vastly differ in their sizes distributions across the genome. Here, we identify genomic features SV classes STRs that are associated with gene expression complex traits, including locations relative to eGenes, likelihood being multiple eGene types (e.g., coding, noncoding, level evolutionary constraint), effect sizes, linkage disequilibrium tagging single nucleotide used GWAS, GWAS...
PurposeThis study aimed to provide comprehensive diagnostic and candidate analyses in a pediatric rare disease cohort through the Genomic Answers for Kids program.MethodsExtensive of 960 families with suspected genetic disorders included short-read exome sequencing genome (srGS); PacBio HiFi long-read (HiFi-GS); variant calling single nucleotide variants (SNV), structural (SV), repeat variants; machine-learning prioritization. Structured phenotypes, prioritized variants, pedigrees were...
Abstract The extravillous trophoblast cell lineage is a key feature of placentation and successful pregnancy. Knowledge transcriptional regulation driving development limited. Here, we map the transcriptome epigenome landscape as well chromatin interactions human stem cells their transition into cells. We show that integrating accessibility, long-range interactions, transcriptomic, transcription factor binding motif enrichment enables identification factors regulatory mechanisms critical for...
Next-generation sequencing-based assays are being increasingly used in the clinical setting for detection of somatic variants solid tumors, but limited data available regarding interlaboratory performance these assays.To examine proficiency testing from initial College American Pathologists (CAP) Next-Generation Sequencing Solid Tumor survey to report on laboratory performance.CAP results 111 laboratories were analyzed accuracy and associated assay characteristics.The overall observed all...
Structural variants (SVs) and short tandem repeats (STRs) are important sources of genetic diversity but not routinely analyzed in studies because they difficult to accurately identify genotype. Because SVs STRs range size type, it is necessary apply multiple algorithms that incorporate different types evidence from sequencing data employ complex filtering strategies discover a comprehensive set high-quality reproducible variants. Here we assemble 719 deep whole genome (WGS) samples (mean...
Abstract Rare genetic variation is abundant in the human genome, yet identifying functional rare variants and their impact on traits remains challenging. Measuring aberrant gene expression has aided functional, large-effect variants. Here, we expand detection of genetically driven transcriptome abnormalities by evaluating integrating expression, allele-specific alternative splicing from multi-tissue RNA-sequencing data. We demonstrate that each signal informs unique classes further develop...
We assessed the challenging process of recruiting primary care practices in a practice-based research study.In this descriptive case study recruitment data collected for large (TRANSLATE CKD), 48 single or multiple-site health organizations USA with total 114 were invited to participate. quantitative and qualitative measures outcomes first 25 recruited. Information about 13 additional is not provided due staff transitions limited collection resources.Initial outreach was made (from...
Practice-based research continues to evolve and has become a major methodology for many pragmatic studies. While early practice-based network projects were usually short term, current studies often introduce or compare practice innovations that require long-term evaluation. That change requires sites remain engaged in work up 5 years, time can allow significant "voltage drop," decline active participation.Over the past 15 years we have developed adapted several strategies facilitate...
Abstract Identifying regulatory genetic effects in pluripotent cells provides important insights into disease variants with potentially transient or developmental origins. Combining existing and newly-generated data, we characterized 1,367 iPSC lines from 948 unique donors, collectively analyzed within the “Integrated QTL” (i2QTL) Consortium. The sample size of our study allowed us to derive most comprehensive map quantitative trait loci (QTL) human date. We mapped nearby common on five...
Abstract Background Adult immunization rates are below Healthy People 2020 targets. Our objective was to evaluate the effectiveness of a multicomponent intervention improve adult rates. Methods This prospective interventional before-and-after non-randomized study conducted through American Academy Family Physicians National Research Network with 43 primary care physicians from large multi-specialty healthcare organization (multicomponent group n = 23; comparator 20) in United States. The...
Introduction Chronic inflammation of the gastrointestinal tissues underlies inflammatory disorders, leading to tissue damage and a constellation painful debilitating symptoms. These disorders include bowel diseases (Crohn’s disease ulcerative colitis), eosinophilic (eosinophilic esophagitis duodenitis). Gastrointestinal can often present with overlapping symptoms necessitating use invasive procedures give an accurate diagnosis. Methods This study used peripheral blood mononuclear cells from...
Abstract RNA sequencing (RNA-seq) is a complementary approach for Mendelian disease diagnosis patients in whom exome-sequencing not informative. For both rare neuromuscular and mitochondrial disorders, its application has improved diagnostic rates. However, the generalizability of this to diverse diseases yet be evaluated. We sequenced whole blood from 56 cases with undiagnosed spanning 11 categories evaluate general RNA-seq diagnosis. developed robust compare existing large sets controls...
ABSTRACT The extravillous trophoblast ( EVT ) cell lineage is a key feature of placentation and successful pregnancy. Knowledge transcriptional regulation driving development limited. Here, we mapped the transcriptome epigenome landscape as well chromatin interactions human stem TS cells their transition into cells. Integration accessibility, long-range interactions, transcriptomic, transcription factor TF binding motif enrichment enabled identification TFs regulatory mechanisms associated...
Abstract Structural variants (SVs) and short tandem repeats (STRs) comprise a broad group of diverse DNA which vastly differ in their sizes distributions across the genome. Here, we show that different SV classes STRs differentially impact gene expression complex traits. Functional differences between include genomic locations relative to eGenes, likelihood being associated with multiple eGene types (e.g., coding, noncoding, level evolutionary constraint), effect sizes, linkage...
Summary Polygenic risk scores (PRS) aim to quantify the contribution of multiple genetic loci an individual’s likelihood a complex trait or disease. However, existing PRS estimate liability using common variants, excluding impact rare variants. We identified rare, large-effect variants in individuals with outlier gene expression from GTEx project and then assessed their on predictions UK Biobank (UKB). observed large deviations PRS-predicted phenotypes for carriers variants; example,...
Emerging evidence implicates common genetic variation - aggregated into polygenic scores (PGS) impacting the onset and phenotypic presentation of rare diseases. In this study, we quantified individual liability for 1,151 previously published PGS in a cohort 2,374 probands enrolled Genomic Answers Kids (GA4K) disease revealing widespread associations between phenotypes PGSs complex diseases traits, blood protein levels, brain other organ morphological measurements. We observed increased...