DeCompress: tissue compartment deconvolution of targeted mRNA expression panels using compressed sensing

Targeted mRNA expression panels, measuring up to 800 genes, are used in academic and clinical settings due to low cost and high sensitivity for archived samples. Most samples assayed on targeted panels originate from bulk tissue comprised of many cell types, and cell-type heterogeneity confounds biological signals. Reference-free methods are used when cell-type-specific expression references are unavailable, but limited feature spaces render implementation challenging in targeted panels. Here, we present DeCompress, a semi-reference-free deconvolution method for targeted panels. DeCompress leverages a reference RNA-seq or microarray dataset from similar tissue to expand the feature space of targeted panels using compressed sensing. Ensemble reference-free deconvolution is performed on this artificially expanded dataset to estimate cell-type proportions and gene signatures. In simulated mixtures, four public cell line mixtures, and a targeted panel (1199 samples; 406 genes) from the Carolina Breast Cancer Study, DeCompress recapitulates cell-type proportions with less error than reference-free methods and finds biologically relevant compartments. We integrate compartment estimates into cis-eQTL mapping in breast cancer, identifying a tumor-specific cis-eQTL for CCR3 (C–C Motif Chemokine Receptor 3) at a risk locus. DeCompress improves upon reference-free methods without requiring expression profiles from pure cell populations, with applications in genomic analyses and clinical settings.     

Characteristics and Relationships of Mercury-Resistant Mutants and Methionine Auxotrophs of Yeast

Approximately one-half of the mutants of Saccharomyces cerevisiae that are selected as resistant to methyl mercury are also found to require methionine. Eighty-four percent of these met mutations occur at the met15 locus, and the remaining 16% occur at the met2 locus. Surprisingly, the methionine-requiring mutants are recovered at a much higher frequency on methionineless media than on media supplemented with methionine. Growth patterns of the met mutants on media having a continuous concentration gradient of methionine and mercury compounds indicate that, at a critical concentration of the mercury compounds, the methionine requirement of certain met mutants is partially or completely alleviated. This was found for met2, met15, and to a lesser extent for met6, but not for any other methionine mutants. This loss of methionine requirement is produced with methyl mercury, phenyl mercury, and mercuric chloride although met2 and met15 strains can be shown to be resistant only to methyl mercury. Other methionine auxotrophs are not resistant to any of the three mercury compounds. The met2 and met15 mutants, but not the other methionine auxotrophs, develop a sheen of an unidentified product when grown on media with mercuric chloride but not with methyl mercury or phenyl mercury. It is suggested that met2 and met15 mutants produce a simple diffusible substance, which detoxifies methyl mercury, which reacts with mercuric chloride to produce a sheen, and which is the cause of the methionine requirement.     

Studies on cold pressor response of subjects who suffered from frostbite at high altitude

Seven lowlander soldiers who had 1st to 3rd degree of frostbite and 8 lowlander soldiers who recovered from high altitude pulmonary oedema were tested for cold pressor response at 260 m, 26°C, 6.8°C and 4,085 m, 26°C, 6.8°C. 8 lowlander soldiers (Control subjects) of comparable age group were tested for their cold pressor response at 260 m, 26°C and 3,300 m, 26°C. Another group of control subjects from the laboratory were also tested at 2,121 m, 26°C. There was a highly significant decrease in cold pressor response of the frostbite subjects at 260 m, 26°C and a very significant increase at 260 m, 6.8°C as compared to non-frostbite subjects. The subjects who recovered from high altitude pulmonary oedema did not show significant differences as compared with the control subjects. The results suggest certain basic physiological differences in regulation of supply of blood to the extremities under condition of general and local cold exposure.