In a new report, Global Industry Analysts, Inc., charts the future of next-generation sequencing, saying its clinical relevance — in particular, medical information gleaned from resequencing applications for oncology and virology research — is likely to increase over time. GIA says that next-gen sequencing technologies "are expected to continue impinging upon the usage of DNA microarray until the costs come down." The firm adds that "further expansion of the NGS [next-gen sequencing] market is expected to be fueled by product cycles in the market, [and the] broadening of applications carried out by the sequencer to replace associated products such as gene expression arrays."

In a Clinical Chemistry Q&A, the National Institute of Arthritis and Musculoskeletal and Skin Diseases' Michael Ward says that for genetic markers of autoimmune diseases like rheumatoid arthritis to be used in clinical practice, they "should provide unique information about prognosis or treatment response not provided by other more readily available and less expensive sources, be it the clinical history or examination, or more commonly used laboratory tests." He notes that while markers of potential drug toxicity are already being used in some cases, currently "no genetic markers are used clinically for prognosis or to guide treatment decisions." Plus, Ward adds, "heterogeneity in symptoms, signs, and responses to treatment among patients of the same genotype will complicate these efforts."

However, to Ward's mind, "the trend in the diagnostics in autoimmune diseases is clearly toward 'omics." And so, as the technologies advance, "it may be possible to identify specific autoantibody profiles, for example, that could lead to more accurate or earlier diagnosis," he says, adding that at the same time, "treatments will increasingly be individualized and chosen on the basis of knowledge of the prime mediators of inflammation in a particular patient."

Researchers from the UK Health Protection Agency present in a Journal of Medical Microbiology paper published online in advance a real-time PCR assay targeting the cylB gene to detect Streptococcus agalactiae in clinical samples. In their paper, the HPA researchers write that "this real-time PCR assay was shown to be superior to culture methods for detection of GBS [Lancefield group B Streptococcus] from CSF [cerebrospinal fluid] and EDTA blood samples."

Study co-author Aruni De Zoysa tells The Telegraph that her group's new, PCR-based test is better than existing tests, which are "time-consuming and can sometimes be unreliable." De Zoysa adds that though it is still in the early stages of development, her group's test "is an invaluable tool that is based on detecting DNA, which makes diagnosis far more accurate and allows us to get results much faster. ... As there is no vaccine at present for GBS, rapid and accurate detection of the GBS bacterium is crucial to reduce the risk of infant deaths from GBS infection."

Researchers in Barcelona, Spain, this week present an assessment of the feasibility of a "nanofluidic digital PCR array platform to detect and quantify KRAS mutations simultaneously in clinically relevant samples." Using Fluidigm's Digital Array Chip, the team examined two groups of patients — the first consisting of 27 patients with colorectal carcinomas, 14 with adenomas, and five controls; the second consisting of 42 patients with pancreatic carcinomas, four with adenocarcinomas of the ampulla, and six with chronic pancreatitis. In a Clinical Chemistry paper published online in advance this week, the researchers report having found that "digital PCR provides a robust, quantitative measure of the proportion of KRAS mutant alleles in routinely obtained samples."

Over in this week's issue, New York Presbyterian Hospital's Francesca Khani and Mikhail Roshal from Weill Cornell Medical College present a clinical case study in which a 24-year-old man who had been diagnosed with hemophilia early in life presented to the clinic for follow-up after a recent hospitalization for excessive bleeding, noting a history of prolonged bleeding, a previous upper GI bleed, excessive bruising, and chronic pain in his ankles and joints. Khani and Roshal add that "the patient's family history is noteworthy for consanguineous parents (first cousins) and a sister who also experienced excessive bleeding, although her diagnosis was uncertain." Taken with the patient's coagulation test results, the researchers deduced that he might have F5F8D — an autosomal recessive disorder that affects approximately 1 in 1,000,000 in the general population. "F5F8D is genetically distinct from isolated inherited deficiencies of factor VIII (hemophilia A) and factor V (parahemophilia)," the authors write in Clinical Chemistry, adding that "currently, mutations in either of two genes, LMAN1 and MCFD2, are believed to account for all cases of F5F8D."

Ronald Dorfman — emeritus professor of pathology at the Stanford University School of Medicine — has died, Stanford says in a press release. He was 89. Dorfman made his mark studying diseases of the lymph nodes and hematopoietic cells, and was celebrated for his diagnostic skill, Stanford says. He also helped to develop the subspecialty of hematopathology, co-founded the Society for Hematopathology in 1981, and was instrumental in developing a classification system for lymphoma, the school adds. According to Stanford, "the physicians’ efforts transformed the once fatal disease into one of the most curable forms of cancer."

In Experimental and Molecular Pathology, researchers in the US, the UK, and Japan describe their method for the identification of anti-renal antibodies in patients with age-related macular degeneration. "In order to reveal retinal antigens targeted by serum IgG from AMD patients, mouse retinal tissue proteins were separated by 2-dimensional electrophoresis and the proteins in the immunoblots that were specific for dry and wet AMD patients' IgG were identified by LC-MS/MS," the team says. They found that retinol-binding protein 3 and aldolase C were mostly recognized by IgG from wet AMD patients and that pyruvate kinase M2 was targeted by both dry and wet AMD. Further, the team adds, "level of anti-PKM2 IgG antibody was correlated best with the stage of AMD." This suggests that the serum from an AMD patient contains auto-antibodies against retinal proteins, and that anti-PKM2 IgG could be used as a biomarker for AMD diagnosis and prognosis.

Also in Experimental and Molecular Pathology, researchers in Australia and the US report that the activation of endothelial cells promotes monocytes' formation of foam cells, a pathological feature of atherosclerosis. Using an existing in vitro model of transendothelial migration, the team found that monocytes undergo transendothelial migration "across a primary endothelial monolayer into an underlying three-dimensional collagen matrix in the presence of 20 percent human serum." This, the researchers say, demonstrates that in the absence of additional lipids, sub-endothelial monocytes can develop into foam cells within 48 hours of transendothelial migration across TNF-α activated endothelium. "Our data indicate a role for both monocyte-endothelial interactions and soluble factors in the regulation of foam cell development, including oxidation of LDL in situ from lipid present in culture medium following TNF-α stimulation of the endothelial cells," they add.