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This Week in Genome Research: Apr 14, 2010

In a paper published online in advance in Genome Research this week, researchers describe their high-throughput method for interrogating transcription factor binding specificity, based on systematic evolution of ligands — or SELEX — by exponential enrichment and massively parallel sequencing of proteins expressed in mammalian cells. "The method is optimized for analysis of large number of TFs in parallel through the use of affinity tagged proteins, barcoded selection oligonucleotides and multiplexed sequencing," the authors write, adding that their method allows for higher throughput than traditional microarray-based methods.

Valer Gotea, Axel Visel, and their colleagues report that homotypic clusters of transcription factor binding sites "are a pervasive feature of human cis-regulatory modules," and may "play an important role in gene regulation in the human and other vertebrate genomes." In their investigations, Gotea and Visel et al. used known binding motifs for transcription factors in the human, mouse, chicken, and fugu genomes and a hidden Markov model-based approach to decipher homotypic clusters of binding sites. "We found that evolutionarily conserved HCTs occupy nearly 2% of the human genome, with experimental evidence for individual TFs supporting their binding to predicted HCTs," the team writes.

Researchers in France present the results of their genomic, proteomic, and transcriptomic analysis of Rickettsia prowazekii — the agent of epidemic typhus, which exists in strains of varied virulence. They found that differential virulence was associated with the "up-regulation of antiapoptotic genes or the interferon I pathway in the host cells," and surface protein expression and methylation. "An area of genomic plasticity appears to determine virulence in R. prowazekii and represents an example of adaptive mutation for this pathogen," the authors conclude.

In another article published online in advance, an international research team describes their investigation of structural variant breakpoints in the mouse genome. In applying their algorithm for genome-wide mapping and assembly of SV breakpoints to two inbred mouse strains, they "report 7196 SVs between the two strains, more than two-thirds of which are due to transposon insertions." They also found that SVs are "significantly enriched in regions of segmental duplication," independent of sequence homology, suggesting that "the genetic instability of such regions is often the cause rather than the consequence of duplicated genomic architecture."

The Scan

Long COVID-19 Susceptibility Clues Contained in Blood Plasma Proteome

A longitudinal study in eBioMedicine found weeks-long blood plasma proteome shifts after SARS-CoV-2 infection, along with proteomic signatures that appeared to coincide with long Covid risk.

Tibetan Study Finds Adaptive Variant Influencing Skin Pigmentation

With a combination of phenotyping and genetic data, researchers document at PNAS a Tibetan-enriched enhancer variant influencing melanin synthesis and ultraviolet light response.

Domestication Linked to Nervous System Genes in Inbred Mouse Strains

Researchers highlighted more than 300 positively selected genes in domesticated mice, including genes linked to nervous system function or behavior in Genome Biology.

ALS Genetic Testing May Be Informative Across Age Ranges, Study Finds

Researchers in the journal Brain identified clinically actionable variants in a significant subset of older ALS patients, prompting them to point to the potential benefits of broader test use.