Directed evolution of an orthogonal transcription engine for programmable gene expression in eukaryotes.

T7 RNA polymerase (RNAP) has enabled orthogonal control of gene expression and recombinant protein production across diverse prokaryotic host chassis organisms for decades. However, the absence of 5' methyl guanosine caps on T7 RNAP-derived transcripts has severely limited its utility and widespread adoption in eukaryotic systems. To address this shortcoming, we evolved a fusion enzyme combining T7 RNAP with the single subunit capping enzyme from African swine fever virus using .

Blood absolute lymphocyte count and trajectory are important in understanding severe COVID-19.

Background: Low blood absolute lymphocyte count (ALC) may predict severe COVID-19 outcomes. Knowledge gaps remain regarding the relationship of ALC trajectory with clinical outcomes and factors associated with lymphopenia.

Methods: Our post hoc analysis of the Therapeutics for Inpatients with COVID-19 platform trial utilized proportional hazards models to assess relationships between Day (D) 0 lymphopenia (ALC < 0.

Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.

Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. We report analyses of rare variants that impact birth weight when carried by either fetus or mother, using whole exome sequencing data in up to 234,675 participants. Rare protein-truncating and deleterious missense variants are collapsed to perform gene burden tests.

Using Family History Data to Improve the Power of Association Studies: Application to Cancer in UK Biobank.

In large cohort studies the number of unaffected individuals outnumbers the number of affected individuals, and the power can be low to detect associations for outcomes with low prevalence. We consider how including recorded family history in regression models increases the power to detect associations between genetic variants and disease risk. We show theoretically and using Monte-Carlo simulations that including a family history of the disease, with a weighting of 0.