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 To see one of Swift’s many publication references, simply expand each accordion section below.

Differences between germline and somatic mutation rates in humans and mice

Nat Commun. 2017 May 9;8:15183. doi: 10.1038/ncomms15183.

The germline mutation rate has been extensively studied and has been found to vary greatly between species, but much less is known about the somatic mutation rate in multicellular organisms, which remains very difficult to determine. Presented is data on somatic mutation rates in mice and humans, obtained by sequencing single cells and clones derived from primary fibroblasts, which allows us to make the first direct comparison with germline mutation rates in these two species. The results indicate that the somatic mutation rate is almost two orders of magnitude higher than the germline mutation rate…more »

Zika virus evolution and spread in the Americas

bioRxiv preprint first posted online Feb. 18, 2017; doi:

Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak…more »

Accurate identification of single-nucleotide variants in whole-genome-amplified single cells

Nat Methods. 2017 May;14(5):491-493. doi: 10.1038/nmeth.4227. Epub 2017 Mar 20.

Mutation analysis in single-cell genomes is prone to artifacts associated with cell lysis and whole-genome amplification. Here we addressed these issues by developing single-cell multiple displacement amplification (SCMDA) and a general-purpose single-cell-variant caller, SCcaller. By comparing SCMDA-amplified single cells with unamplified clones from the same population, we validated the procedure as a firm foundation for standardized somatic-mutation analysis in single-cell genomics….more »

Cell-free DNA and next-generation sequencing in the service of personalized medicine for lung cancer

Oncotarget. 2016 Aug 30. DOI: 10.18632/oncotarget.11717

Personalized medicine has emerged as the future of cancer care to ensure that patients receive individualized treatment specific to their needs. In order to provide such care, molecular techniques that enable oncologists to diagnose, treat, and monitor tumors are necessary. In the field of lung cancer, cell free DNA (cfDNA) shows great potential as a less invasive liquid biopsy technique, and next-generation sequencing (NGS) is a promising tool for analysis of tumor mutations…. more »

Vasculogenic mimicry in small cell lung cancer

Nat Commun. 2016 Nov 9;7:13322.

Small cell lung cancer (SCLC) is characterized by prevalent circulating tumour cells (CTCs), early metastasis and poor prognosis. We show that SCLC patients (37/38) have rare CTC subpopulations co-expressing vascular endothelial-cadherin (VE-cadherin)…. more »

A comparative study of ChIP-seq sequencing library preparation methods

BMC Genomics (2016) 17:816.

ChIP-seq is the primary technique used to investigate genome-wide protein-DNA interactions. As part of this procedure, immunoprecipitated DNA must undergo “library preparation” to enable subsequent high-throughput sequencing…. more »

Cell cycle progression in Caulobacter requires a nucleoid-associated protein with high AT sequence recognition

Proc Natl Acad Sci U S A. 2016 Sep 19. pii: 201612579.

In all organisms, morphological and functional diversity is the product of cell type-specific genetic programs. Asymmetric cell division in Caulobacter yields daughter cells that differ functionally due to the differential read-out of their genomes…. more »

Distinct sub-clonal tumour responses to therapy revealed by circulating cell-free DNA

Ann Oncol (2016). doi: 10.1093/annonc/mdw278. First published online: August 8, 2016.

The application of precision medicine in oncology requires in-depth characterisation of a patient’s tumours and the dynamics of their responses to treatment. We used next generation sequencing of circulating cell-free DNA to monitor the response of a KIT p.L576P-mutant metastatic vaginal mucosal melanoma to sequential targeted, immuno- and chemotherapy…. more »

Digital sorting of pure cell populations enables unambiguous genetic analysis of heterogeneous formalin-fixed paraffin-embedded tumors by next generation sequencing

Sci Rep. 2016 Feb 11;6:20944. doi: 10.1038/srep20944.

Precision medicine in oncology requires an accurate characterization of a tumor molecular profile for patient stratification. Though targeted deep sequencing is an effective tool to detect the presence of somatic sequence variants, a significant number of patient specimens do not meet the requirements needed for routine clinical application… more »

Application of sequencing, liquid biopsies, and patient-derived xenografts for personalized medicine in melanoma

Cancer Discov. 2016 Mar;6(3):286-99. doi: 10.1158/2159-8290. CD-15- 1336. Epub 2015 Dec 29.

Targeted therapies and immunotherapies have transformed melanoma care, extending median survival from ∼9 to over 25 months, but nevertheless most patients still die of their disease. The aim of precision medicine is to tailor care for individual patients and improve outcomes… more »

Genome sequence of Klebsiella pneumoniae urinary tract isolate Top52

Genome Announc. 2(4):e00668-14. doi:10.1128/genomeA.00668-14.

Klebsiella pneumoniae is a significant cause of nosocomial infections, including ventilator-associated pneumonias and catheter-associated urinary tract infections. K. pneumoniae strain TOP52 #1721 (Top52) was isolated from a woman presenting with acute cystitis and subsequently characterized using various murine models of infection… more »

Genome sequence of Klebsiella pneumoniae respiratory isolate IA565

Genome Announc. 2(5):e00896-14. doi:10.1128/genomeA.00896-14.

Klebsiella pneumoniae is a clinically significant opportunistic bacterial pathogen as well as a normal member of the human microbiota. K. pneumoniae strain IA565 was isolated from a tracheal aspirate at the University of Iowa Hospitals and Clinics… more »

Study of preanalytic and analytic variables for clinical next-generation sequencing of circulating cell-free nucleic acid

J Mol Diagn. 2017 May 12. pii: S1525-1578(17)30027-2. doi: 10.1016/j.jmoldx.2017.03.003. [Epub ahead of print]

Detection of mutations in plasma circulating cell-free DNA (cfDNA) by next-generation sequencing (NGS) has opened up new possibilities for monitoring treatment response and disease progression in patients with solid tumors. However, implementation of cfDNA genotyping in diagnostic laboratories requires systematic assessment of preanalytical parameters and analytical performance of NGS platforms. We assessed the effects of peripheral blood collection tube and plasma separation time on cfDNA yield and integrity and performance of the Ion PGM, Proton, and MiSeq NGS platforms…. more »

Comparison of BEAMing assays and competitive approaches in the detection of main alteration of RAS in circulating DNA of non small-cell lung cancer (NSCLC) and metastatic colon cancer. Manuscript 2016

J Clin Oncol 35, no. 15_suppl – published online before print. DOI: 10.1200/JCO.2017.35.15_suppl.e23056

A number of RAS mutations confer resistance to anti-EGFR therapies routinely used in the treatment of colon cancer. The objective of this study was to evaluate the pertinence of analyzing circulating-free plasma DNA (cfDNA) as an indicator of the mutational status of a tumor, in order to use liquid biopsies instead of invasive and painful tumor biopsies during tumor progression…. more »

Genomic analysis of uterine lavage fluid detects early endometrial cancers and reveals a prevalent landscape of driver mutations in women without histopathologic evidence of cancer: a prospective cross-sectional study

PLoS Med. 2016 Dec 27;13(12):e1002206. doi: 10.1371/journal.pmed.1002206. eCollection 2016

Endometrial cancer is the most common gynecologic malignancy, and its incidence and associated mortality are increasing. Despite the immediate need to detect these cancers at an earlier stage, there is no effective screening methodology or protocol for endometrial cancer….Based on these cancer genome results, and in a prospective study, we hypothesized that the use of ultra-deep, targeted gene sequencing could detect somatic mutations…. more »

Cell-free DNA and next-generation sequencing in the service of personalized medicine for lung cancer

Oncotarget. 2016 Aug 30. DOI: 10.18632/oncotarget.11717

Personalized medicine has emerged as the future of cancer care to ensure that patients receive individualized treatment specific to their needs. In order to provide such care, molecular techniques that enable oncologists to diagnose, treat, and monitor tumors are necessary. In the field of lung cancer, cell free DNA (cfDNA) shows great potential as a less invasive liquid biopsy technique, and next-generation sequencing (NGS) is a promising tool for analysis of tumor mutations…. more »

Risk stratification of Barrett’s oesophagus using a non-endoscopic sampling method coupled with a biomarker panel: a cohort study

Lancet. 2016, Nov 10; doi: 10.1016/S2468-1253(16)30118-2.

…FFPE-extracted DNA was quantified by PCR with primers specific to ALU115 repetitive elements (appendix 1, p 1). At least 10-25 ng quantified DNA was used for library preparation with TP53 Accel-Amplicon comprehensive panel (Swift Biosciences, Ann Arbor, MI, US)…more »

Newborn screening quality assurance program for CFTR mutation detection and gene sequencing to identify Cystic Fibrosis

Journal of Inborn Errors of Metabolism & Screening. 2016, Volume 4:1-11.

All newborn screening laboratories in the United States and many worldwide screen for cystic fibrosis. Most laboratories use a second-tier genotyping assay to identify a panel of mutations in the CF transmembrane regulator (CFTR) gene… more »

CancerLocator: non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA

Genome Biology 2017 18:53. DOI: 10.1186/s13059-017-1191-5

A probabilistic method, CancerLocator, exploits the diagnostic potential of cell-free DNA by determining not only the presence but also the location of tumors. CancerLocator simultaneously infers the proportions and the tissue-of-origin of tumor-derived cell-free DNA in a blood sample using genome-wide DNA methylation data. CancerLocator outperforms two established multi-class classification methods on simulations and real data, even with the low proportion of tumor-derived DNA in the cell-free DNA scenarios….more »

Cell-free DNA, inflammation, and the initiation of spontaneous term labor

American Journal of Obstetrics and Gynecology (2017), doi: 10.1016/j.ajog.2017.05.027

Hypomethylated cell-free DNA from senescent placental trophoblasts may be involved in the activation of the inflammatory cascade to initiate labor. Objective: To determine the changes in cell-free DNA concentrations, the methylation ratio, and inflammatory markers between women in labor at term vs women without labor. In this prospective cohort study, eligible participants carried a nonanomalous singleton fetus. Women with major medical comorbidity, preterm labor, progesterone use, aneuploidy, infectious disease, vaginal bleeding, abdominal trauma, or invasive procedures during the pregnancy were excluded….more »

SPlinted Ligation Adapter Tagging (SPLAT), a novel library preparation method for whole genome bisulphite sequencing

Nucleic Acids Res. 2017 Apr 7; 45(6): e36. Published online 2016 Nov 29. doi:  10.1093/nar/gkw1110

Sodium bisulphite treatment of DNA combined with next generation sequencing (NGS) is a powerful combination for the interrogation of genome-wide DNA methylation profiles. Library preparation for whole genome bisulphite sequencing (WGBS) is challenging due to side effects of the bisulphite treatment, which leads to extensive DNA damage. Recently, a new generation of methods for bisulphite sequencing library preparation have been devised. They are based on initial bisulphite treatment of the DNA….more »

Targeted bisulfite sequencing of the dynamic DNA methylome

Epigenetics & Chromatin 2016 9:55. Doi: 10.1186/s13072-016-0105-1.

The ability to measure DNA methylation precisely and efficiently continues to drive our understanding of this modification in development and disease. Whole genome bisulfite sequencing has the advantage of theoretically capturing all cytosines in the genome…. more »

Detecting DNA cytosine methylation using nanopore sequencing

Nat Methods. 2017 Apr;14(4):407-410. doi: 10.1038/nmeth.4184. Epub 2017 Feb 20

In nanopore sequencing devices, electrolytic current signals are sensitive to base modifications, such as 5-methylcytosine (5-mC). Here we quantified the strength of this effect for the Oxford Nanopore Technologies MinION sequencer. By using synthetically methylated DNA, we were able to train a hidden Markov model to distinguish 5-mC from unmethylated cytosine. We applied our method to sequence the methylome of human DNA, without requiring special steps for library preparation…. more »

The 1.78-kb insertion in the 3′-untranslated region of RXFP2 does not segregate with horn status in sheep breeds with variable horn status

Genet Sel Evol. 2016 Oct 19;48(1):78

The mode of inheritance of horn status in sheep is far more complex than a superficial analysis might suggest. Observations, which were mostly based on crossbreeding experiments, indicated that the allele that results in horns is dominant in males and recessive in females, and some authors even speculated about the involvement of more than two alleles. However, all recent genome-wide association analyses point towards a very strong effect of a single autosomal locus on ovine chromosome 10…. more »

Chapter Eight – Sequencing DNA for the oxidatively modified base 8-Oxo-7,8-Dihydroguanine

Methods Enzymol. 2017;591:187-210. doi: 10.1016/bs.mie.2017.03.004. Epub 2017 Apr 7

The DNA base guanine (G) can be oxidatively modified to 8-oxo-7,8-dihydroguanine (OG). Extraction of genomic DNA followed by nuclease digestion and mass spectrometry analysis has found OG is present at background levels of ~ 1 out of 106 Gs; however, this approach cannot determine the locations for the OGs in the genome. Thus, in this methods report, we outline three different methods (A, B, and C) for sequencing OG in DNA… more »

Single-stranded DNA library preparation preferentially enriches short maternal DNA in maternal plasma

Clin Chem. 2017 May;63(5):1031-1037. doi: 10.1373/clinchem.2016.268656. Epub 2017 Mar 9

Recent studies have suggested that single-stranded DNA (ssDNA) library preparation can enrich short DNA species from the plasma of healthy individuals, cancer patients, and transplant recipients. Based on previous observations that fetal DNA molecules in the maternal plasma are shorter than maternal DNA molecules, ssDNA library preparation may potentially enrich fetal DNA and provide substantial improvement in noninvasive prenatal testing… more »

Sequencing historical specimens: successful preparation of small specimens with low amounts of degraded DNA

Mol Ecol Resour. 2017 Feb 15. doi: 10.1111/1755-0998.12660. [Epub ahead of print]

Despite advances that allow DNA sequencing of old museum specimens, sequencing small-bodied, historical specimens can be challenging and unreliable as many contain only small amounts of fragmented DNA. Dependable methods to sequence such specimens are especially critical if the specimens are unique. We attempt to sequence small-bodied (3–6 mm) historical specimens (including nomenclatural types) of beetles that have been housed, dried, in museums for 58–159 years, and for which few or no suitable replacement specimens exist… more »

Towards quantitative viromics for both double-stranded and single-stranded DNA viruses

Peer J 4:e2777. doi: 10.7717/peerj.2777

Viruses strongly influence microbial population dynamics and ecosystem functions. However, our ability to quantitatively evaluate those viral impacts is limited to the few cultivated viruses and double-stranded DNA (dsDNA) viral genomes captured in quantitative viral metagenomes (viromes). This leaves the ecology of non-dsDNA viruses nearly unknown, including single-stranded DNA (ssDNA) viruses that have been frequently observed in viromes… more »

Single-stranded DNA phages: from early molecular biology tools to recent revolutions in environmental microbiology

FEMS Microbiol Lett. 2016 Mar;363(6). pii: fnw027. doi: 10.1093/femsle/fnw027. Epub 2016 Feb 5.

Single-stranded DNA (ssDNA) phages are profoundly different from tailed phages in many aspects including the nature and size of their genome, virion size and morphology, mutation rate, involvement in horizontal gene transfer, infection dynamics and cell lysis mechanisms. Despite the importance of ssDNA phages as molecular biology tools and model systems, the environmental distribution and ecological roles of these phages have been largely unexplored… more »

GATA2 deficiency in children and adults with severe pulmonary alveolar proteinosis and hematologic disorders

BMC Pulm Med. 2015 Aug 12;15:87. doi: 10.1186/s12890-015-0083-2.

The majority of cases with severe pulmonary alveolar proteinosis (PAP) are caused by auto-antibodies against GM-CSF. A multitude of genetic and exogenous causes are responsible for few other cases… more »

Unique synteny and alternate splicing of the chitin synthases in closely related heliothine moths

Gene. 2015 Dec 10;574(1):121-39. doi: 10.1016/j.gene.2015.08.001. Epub 2015 Aug 5.

Chitin is an extracellular biopolymer that contributes to the cuticular structural matrix in arthropods. As a consequence of its rigid structure, the chitinous cuticle must be shed and replaced to accommodate growth… more »

Complete mitochondrial genome of Muricea crassa and Muricea purpurea (Anthozoa: Octocorallia) from the eastern tropical Pacific

bioRxiv. doi:

We sequenced the complete mitogenomes of two eastern tropical Pacific gorgonians, Muricea crassa and Muricea purpurea, using NGS technologies. The assembled mi- togenomes of M. crassa and M. purpurea were 19,586 bp and 19,358 bp in length, with a GC-content ranging from 36.0% to 36.1%, respectively… more »

Genome Sequences of Campylobacter jejuni 81-176 Variants with Enhanced Fitness Relative to the Parental Strain in the Chicken Gastrointestinal Tract

Genome Announc. 2(1):e00006-14. doi:10.1128/genomeA.00006-14.

Campylobacter jejuni is a major cause of food-borne infections in the United States due to its ability to asymptomatically colonize the gastrointestinal tracts of chickens. Using competition assays with parental C. jejuni 81-176, variants with consistently improved fitness in chicken ceca relative to the parental strain were identified and sequenced… more »