Arginine Depletion in Human Cancers

Arginine is encoded by six different codons. Base pair changes in any of these codons can have a broad spectrum of effects including substitutions to twelve different amino acids, eighteen synonymous changes, and two stop codons. Four amino acids (histidine, cysteine, glutamine, and tryptophan) account for over 75% of amino acid substitutions of arginine. This suggests that a mutational bias, or “purifying selection”, mechanism is at work. This bias appears to be driven by C > T and G > A transitions in four of the six arginine codons, a signature that is universal and independent of cancer tissue of origin or histology. Here, we provide a review of the available literature and reanalyze publicly available data from the Catalogue of Somatic Mutations in Cancer (COSMIC). Our analysis identifies several genes with an arginine substitution bias. These include known factors such as IDH1, as well as previously unreported genes, including four cancer driver genes (FGFR3, PPP6C, MAX, GNAQ). We propose that base pair substitution bias and amino acid physiology both play a role in purifying selection. This model may explain the documented arginine substitution bias in cancers.

Elementary Index Bias: Evidence for the Euro Area from a Large Scanner Dataset

We provide evidence on the effect of elementary index choice on inflation measurement in the euro area. Using scanner data for 15,844 individual items from 42 product categories and 10 euro area countries, we compute product category level elementary price indexes using eight different elementary index formulas. Measured inflation outcomes of the different index formulas are compared with the Fisher ideal index to quantify elementary index bias. We have three main findings. First, elementary index bias is quite variable across product categories, countries and index formulas. Second, a comparison of elementary index formulas with and without expenditure weights shows that a shift from price only indexes to expenditure weighted indexes would entail at the product level multiple percentage points differences in measured price changes. And finally, we show that elementary index bias is quantitatively more important than upper level substitution bias.

Divergent pattern of genomic variation in Plasmodium falciparum and P. vivax

The two main species causing malaria in humans, Plasmodium falciparum and P. vivax, differ significantly from each other in their evolutionary response to common drugs, but the reasons for this are not clear. Here we utilized the recently available large-scale genome sequencing data from these parasites and compared the pattern of single nucleotide polymorphisms, which may be related to these differences. We found that there was a five-fold higher preference for AT nucleotides compared to GC nucleotides at synonymous single nucleotide polymorphism sites in P. vivax. The preference for AT nucleotides was also present at non-synonymous sites, which lead to amino acid changes favouring those with codons of higher AT content. The substitution bias was also present at low and moderately conserved amino acid positions, but not at highly conserved positions. No marked bias was found at synonymous and non-synonymous sites in P. falciparum. The difference in the substitution bias between P. falciparum and P. vivax found in the present study may possibly contribute to their divergent evolutionary response to similar drug pressures.