Todd A Richmond

Todd A Richmond
Roche · Research and Development

Genetics PhD, UW-Madison

About

193
Publications
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17,330
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Publications

Publications (193)
Article
Full-text available
Background Clinical laboratories routinely use formalin-fixed paraffin-embedded (FFPE) tissue or cell block cytology samples in oncology panel sequencing to identify mutations that can predict patient response to targeted therapy. To understand the technical error due to FFPE processing, a robustly characterized diploid cell line was used to create...
Article
Full-text available
The primary objective of the FDA-led Sequencing and Quality Control Phase 2 (SEQC2) project is to develop standard analysis protocols and quality control metrics for use in DNA testing to enhance scientific research and precision medicine. This study reports a targeted next-generation sequencing (NGS) method that will enable more accurate detection...
Article
Full-text available
Circulating tumor DNA (ctDNA) sequencing is being rapidly adopted in precision oncology, but the accuracy, sensitivity and reproducibility of ctDNA assays is poorly understood. Here we report the findings of a multi-site, cross-platform evaluation of the analytical performance of five industry-leading ctDNA assays. We evaluated each stage of the ct...
Article
Full-text available
Background Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation o...
Article
Full-text available
Background Oncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and p...
Preprint
The primary objective of the FDA-led Sequencing and Quality Control Phase 2 (SEQC2) project is to develop standard analysis protocols and quality control metrics for use in DNA testing to enhance scientific research and precision medicine. This study reports a targeted next generation sequencing (NGS) method that enables more accurate detection of...
Preprint
Full-text available
Clinical laboratories routinely use formalin-fixed paraffin-embedded (FFPE) tissue or cell block cytology samples in oncology panel sequencing to identify mutations that can predict patient response to targeted therapy. To understand the technical error due to FFPE processing, a robustly characterized normal cell line was used to create FFPE sample...
Article
Full-text available
Over 94 million domestic cats are susceptible to cancers and other common and rare diseases. Whole exome sequencing (WES) is a proven strategy to study these disease-causing variants. Presented is a 35.7 Mb exome capture design based on the annotated Felis_catus_9.0 genome assembly, covering 201,683 regions of the cat genome. Whole exome sequencing...
Article
Osteosarcoma is an aggressive tumor of the bone that primarily affects young adults and adolescents. Osteosarcoma is characterized by genomic chaos and heterogeneity. While inactivation of tumor protein p53 (TP53) is nearly universal other high frequency mutations or structural variations have not been identified. Despite this genomic heterogeneity...
Preprint
Full-text available
Over 94 million domestic cats are considered pets, who, as our companions, are also susceptible to cancers, common and rare diseases. Whole exome sequencing (WES) is a cost-effective strategy to study their putative disease-causing variants. Presented is ~35.8 Mb exome capture design based on the annotated Felis_catus_9.0 genome assembly, covering...
Preprint
Full-text available
Osteosarcoma is an aggressive tumor of the bone that primarily affects young adults and adolescents. Osteosarcoma is characterized by genomic chaos and heterogeneity. While inactivation of tumor suppressor p53 TP53 is nearly universal other high frequency mutations or structural variations have not been identified. Despite this genomic heterogeneit...
Article
Full-text available
Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the brain caused by reactivation of the JC virus (JCV), a polyomavirus that infects at least 60% of the population but is asymptomatic or results in benign symptoms in most people. PML occurs as a secondary disease in a variety of disorders or as a serious adverse...
Article
Full-text available
Background Whole genome shotgun re-sequencing of wheat is expensive because of its large, repetitive genome. Moreover, sequence data can fail to map uniquely to the reference genome making it difficult to unambiguously assign variation. Re-sequencing using target capture enables sequencing of large numbers of individuals at high coverage to reliabl...
Article
Full-text available
Combining high‐throughput sequencing with targeted sequence capture has become an attractive tool to study specific genomic regions of interest. Most studies have so far focused on the exome using short‐read technology. These approaches are not designed to capture intergenic regions needed to reconstruct genomic organization, including regulatory r...
Preprint
Full-text available
Combining high-throughput sequencing with targeted sequence capture has become an attractive tool to study specific genomic regions of interest. Most studies have so far focused on the exome using short-read technology. These approaches are not designed to capture intergenic regions needed to reconstruct genomic organization, including regulatory r...
Preprint
Full-text available
Background Whole genome shotgun re-sequencing of wheat is expensive because of its large, repetitive genome. Moreover, sequence data can fail to map uniquely to the reference genome making it difficult to unambiguously assign variation. Re-sequencing using target capture enables sequencing of large numbers of individuals at high coverage to reliabl...
Data
Table S5. Oligonucleotide Sequence for VHL Exon Amplification and Methylation Specific PCR, Related to STAR Methods
Data
Table S6. Details of Custom Driver Panels (v3, v5, and v6) and Somatic Alterations in TRACERx Cohort, Related to Figure 1
Data
Table S2. Comparison of Driver Event Frequency across TRACERx, HUC, and MSK Cohorts, Related to Figure 1
Data
Table S1. Clinical and Tumor Characteristics of TRACERx, HUC, and MSK Primary Metastasis Pair Patients and Evolutionary Subtypes, Progression Patterns, Treatment of Disease, and Survival Outcomes of TRACERx and PEACE Patients, Related to Figures 1, 4, and 6
Article
Full-text available
Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we...
Chapter
Cytosine methylation has been shown to have a role in a host of biological processes. In mammalian biology these include stem cell differentiation, embryonic development, genomic imprinting, inflammation, and silencing of transposable elements. Given the central importance of these processes, it is not surprising to find aberrant cytosine methylati...
Article
Next generation sequencing (NGS) of enriched targets is increasingly being used to discover and track mutations in genes implicated in cancer. Amplicon-based target enrichment approaches are frequently used with cancer samples because there is no sample library preparation needed and primer-based approaches are typically efficient with sequencing r...
Article
Full-text available
Characterization of the somatic sequence variations that accrue in cells is critical for understanding the pronounced cellular and clinical heterogeneity observed in cancer. The ability to efficiently detect variations in tumors can help to identify biomarkers which may be relevant to clinical trials, support more accurate prognosis, and help guide...
Article
Abstract Cancer is a result of a number of genetic alterations that disturb normal, controlled cell growth and differentiation. Mutational events leading to the activation of oncogenes or the inactivation of tumor-suppressor genes have been linked causally to the formation of tumors. p53 is one of the most important regulators of transcription, ce...
Chapter
Sequencing-based whole-transcriptome analysis (i.e., RNA-Seq) can be a powerful tool when used to measure gene expression, detect novel transcripts, characterize transcript isoforms, and identify sequence polymorphisms. However, this method can be inefficient when the goal is to study only one component of the transcriptome, such as long noncoding...
Article
Full-text available
Serum-to-2i interconversion of mouse embryonic stem cells (mESCs) is a valuable in vitro model for early embryonic development. To assess whether 3D chromatin organization changes during this transition, we established Capture Hi-C with target-sequence enrichment of DNase I hypersensitive sites. We detected extremely long-range intra- and inter-chr...
Article
Full-text available
Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequen...
Article
Full-text available
We present a capture-based approach for bisulfite-converted DNA that allows interrogation of pre-defined genomic locations, allowing quantitative and qualitative assessments of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) at CG dinucleotides and in non-CG contexts (CHG, CHH) in mammalian and plant genomes. We show the technique works r...
Article
Full-text available
Molecular characterization of events is an integral part of the advancement process during genetically modified (GM) crop product development. Assessment of these events is traditionally accomplished by polymerase chain reaction (PCR) and Southern blot analyses. Southern blot analysis can be time-consuming and comparatively expensive and does not p...
Article
Full-text available
DNA methylation can play important roles in the regulation of transposable elements and genes. A collection of mutant alleles for 11 maize (Zea mays) genes predicted to play roles in controlling DNA methylation were isolated through forward- or reverse-genetic approaches. Low-coverage whole-genome bisulfite sequencing and high-coverage sequence-cap...
Patent
Full-text available
The present invention provides methods for optimizing oligonucleotide hybridization probes for use in basic and clinical research. Specifically, the invention involves hybridizing serially diluted genomic sample to the oligonucleotide probes on the array, such that a signal intensity is produced for each of the probes; computationally identifying o...
Data
Full-text available
Coverage distribution of introns.
Data
Number of raw Illumina reads and reads that passed quality control. Table S2. Exome capture read alignment statistics. Table S3. Single nucleotide polymorphisms identified in eight switchgrass genotypes. Table S4. Genes identified with up-copy number variants in seven switchgrass genotypes using exome capture sequencing. Table S5. Genes identified...
Data
Full-text available
Summary of mapping of exome capture probes to the transcriptome design sequences and the switchgrass reference genome Release 0.
Data
Coverage distribution of exons.
Data
Full-text available
Clusters of copy number variants in switchgrass.
Article
Full-text available
Switchgrass (Panicum virgatum) is a polyploid, outcrossing grass species native to North America and has recently been recognized as a potential biofuel feedstock crop. Significant phenotypic variation including ploidy is present across the two primary ecotypes of switchgrass, referred to as upland and lowland switchgrass. The tetraploid switchgras...
Article
Full-text available
Antibodies are of importance for the field of proteomics, both as reagents for imaging cells, tissues and organs, but also as capturing agents for affinity-enrichment in mass spectrometry based techniques. It is important to gain basic insights regarding the binding sites (epitopes) of antibodies and potential cross-reactivity to non-target protein...
Article
Copy number variation (CNV) is a common source of genetic variation that has been implicated in many genomic disorders. This has resulted in the widespread application of genomic microarrays as a first tier diagnostic tool for CNV detection. More recently whole exome sequencing (WES) has proven successful for the detection of clinically relevant po...
Data
Full-text available
Example of a capture target on a WGS contig
Data
Overview of captured samples and detailed mapping and SNP calling statistics.
Data
Full-text available
Flowcharts for assay design, experimental procedures and sequence analysis.
Data
Full-text available
Neighbor-joining tree with H. bulbosum and H. pubiflorum
Data
Quantification of libraries and sequencing on the Illumina HiSeq2000 instrument. Methods S2. TruSeq WGS library preparation.
Article
Full-text available
Advanced resources for genome-assisted research in barley (Hordeum vulgare) including a whole genome shotgun assembly and an integrated physical map have recently become available. These have made studies that aim to assess genetic diversity or to isolate single genes possible by whole genome resequencing and in silico variant detection. However su...
Article
Full-text available
The major histocompatibility complex (MHC) is one of the most variable and gene-dense regions of the human genome. Most studies of the MHC, and associated regions, focus on minor variants and HLA typing, many of which have been demonstrated to be associated with human disease susceptibility and metabolic pathways. However, the detection of variants...
Data
Coverage of whole gene body and exome of the MHC genes by capture sequencing data. (XLSX)
Data
Comparison of MHC capture genotypes and HapMap genotypes for sample NA18532. (XLSX)
Data
The accuracy of HLA typing method using simulated data at different sequencing depth with different sequencing error rate. (XLSX)
Data
HLA alleles typed by PCR based Sanger sequence method and target capture sequence method. (XLSX)
Data
Distribution of variations within different genomics functional regions for three samples. (XLSX)
Data
Comparison of MHC capture genotypes and HapMap genotypes for sample NA18555. (XLSX)
Data
Coverage of the MHC region using 200 bp insert size library. (XLSX)
Data
Comparison of MHC capture SNPs and Illumina 2.5 M genotyping alleles for sample YH. We classified both the MHC capture alleles and the alleles that were called by genotyping into three categories: (1) Hom ref (homozygotes where both alleles are identical to the reference); (2) Hom mut (homozygotes where both alleles differ from the reference); (3)...