RNA-Seq for the detection of gene fusions in solid tumors: development and validation of the JAX FusionSeq™ 2.0 assay.

Whole transcriptome sequencing (RNA-Seq) has gained prominence for the detection of fusions in solid tumors. Here, we describe the development and validation of an in-house RNA-Seq-based test system (FusionSeq™ 2.0) for the detection of clinically actionable gene fusions, in formalin-fixed paraffin-embedded (FFPE) specimens, using seventy tumor samples with varying fusion status.

Evaluation of indicators supporting reproducibility and transparency within cardiology literature.

Objectives: It has been suggested that biomedical research is facing a reproducibility issue, yet the extent of reproducible research within the cardiology literature remains unclear. Thus, our main objective was to assess the quality of research published in cardiology journals by assessing for the presence of eight indicators of reproducibility and transparency.

Methods: Using a cross-sectional study design, we conducted an advanced search of the National Library of Medicine catalogue for publications in cardiology journals.

Molecular profiling of CNS tumors for the treatment and management of disease.

The World Health Organization (WHO) has defined more than 130 distinct central nervous system (CNS) tumor entities, of which glioblastoma is the most fatal primary brain tumor. However, the correlation of the molecular signatures of glioblastoma with clinical significance for precision medicine is not well-known. How, and to what extent these variants may affect clinical decision making remains uncertain.

Mutation Yield of a Custom 212-Gene Next-Generation Sequencing Panel for Solid Tumors: Clinical Experience of the First 260 Cases Tested Using the JAX ActionSeq™ Assay.

Objective: The study aimed to retrospectively evaluate the positive yield rate of a custom 212-gene next-generation sequencing (NGS) panel, the JAX ActionSeq™ assay, used in molecular profiling of solid tumors for precision medicine.

Methods: We evaluated 261 cases tested over a 24-month period including cancers across 24 primary tissue types and report on the mutation yield in these cases.

Results: Thirty-three of the 261 cases (13%) had no detectable clinically significant variants.

Marker genes as predictors of shared genomic function.

Background: Although high-throughput marker gene studies provide valuable insight into the diversity and relative abundance of taxa in microbial communities, they do not provide direct measures of their functional capacity. Recently, scientists have shown a general desire to predict functional profiles of microbial communities based on phylogenetic identification inferred from marker genes, and recent tools have been developed to link the two. However, to date, no large-scale examination has quantified the correlation between the marker gene based taxonomic identity and protein coding gene conservation.

Technical and Regulatory Considerations for Taking Liquid Biopsy to the Clinic: Validation of the JAX PlasmaMonitor Assay.

The standard of care in oncology has been genomic profiling of tumor tissue biopsies for the treatment and management of disease, which can prove to be quite challenging in terms of cost, invasiveness of procedure, and potential risk for the patient. As the number of available drugs in oncology continues to increase, so too does the demand for technologies and testing applications that can identify genomic alterations targetable by these new therapies. Liquid biopsies that use a blood draw from the diseased patient may offset the many disadvantages of the invasive procedure.

PALADIN: protein alignment for functional profiling whole metagenome shotgun data.

Motivation: Whole metagenome shotgun sequencing is a powerful approach for assaying the functional potential of microbial communities. We currently lack tools that efficiently and accurately align DNA reads against protein references, the technique necessary for constructing a functional profile. Here, we present PALADIN-a novel modification of the Burrows-Wheeler Aligner that provides accurate alignment, robust reporting capabilities and orders-of-magnitude improved efficiency by directly mapping in protein space.

An SNP-based second-generation genetic map of Daphnia magna and its application to QTL analysis of phenotypic traits.

Background: Although Daphnia is increasingly recognized as a model for ecological genomics and biomedical research, there is, as of yet, no high-resolution genetic map for the genus. Such a map would provide an important tool for mapping phenotypes and assembling the genome. Here we estimate the genome size of Daphnia magna and describe the construction of an SNP array based linkage map.

Achilles tendon biomechanics in response to acute intense exercise.

Achilles tendinopathy is a common disorder and is more prevalent in men. Although differences in tendon mechanics between men and women have been reported, understanding of tendon mechanics in young active people is limited. Moreover, there is limited understanding of changes in tendon mechanics in response to acute exercise.

Intra-genomic variation in the ribosomal repeats of nematodes.

Ribosomal loci represent a major tool for investigating environmental diversity and community structure via high-throughput marker gene studies of eukaryotes (e.g. 18S rRNA).

Measuring Achilles tendon mechanical properties: a reliable, noninvasive method.

The purpose of this technical report is to describe a cost-effective and highly reliable methodology to measure mechanical and material properties of the Achilles tendon. Subjects are positioned on an isokinetic dynamometer time synchronized to a diagnostic ultrasound device. A tendon fascicle distal to the soleus is visualized during a ramped isometric maximal plantarflexion contraction.

Simple sequence repeat variation in the Daphnia pulex genome.

Background: Simple sequence repeats (SSRs) are highly variable features of all genomes. Their rapid evolution makes them useful for tracing the evolutionary history of populations and investigating patterns of selection and mutation across genomes. The recently sequenced Daphnia pulex genome provides us with a valuable data set to study the mode and tempo of SSR evolution, without the inherent biases that accompany marker selection.

Transforming the fall-injury risk assessment tool from paper to electronic.

In order to ensure the highest possible safety for our patients, we identified a need to introduce a falls risk assessment tool with high sensitivity, specificity and reliability within our institution. A comparative research study was conducted which evaluated several instruments against actual patient falls. Based on the findings a new instrument was selected and converted to an electronic format compatible with existing nursing informatics systems.

Developing a clinical informatics system which supports a model of partnership among caregivers, patients, and families.

Partnership Care Delivery is an evidence-based practice model being developed at this institution. It emphasizes interdisciplinary collaboration, in which all members of the healthcare team work with the patient as active participants in care processes. In order to achieve true partnership among disciplines, and to engage the patient and family, it was important to create supportive clinical informatics.