The proteomic landscape of genome-wide genetic perturbations.

Functional genomic strategies have become fundamental for annotating gene function and regulatory networks. Here, we combined functional genomics with proteomics by quantifying protein abundances in a genome-scale knockout library in Saccharomyces cerevisiae, using data-independent acquisition mass spectrometry. We find that global protein expression is driven by a complex interplay of (1) general biological properties, including translation rate, protein turnover, the formation of protein complexes, growth rate, and genome architecture, followed by (2) functional properties, such as the connectivity of a protein in genetic, metabolic, and physical interaction networks. Moreover, we show that functional proteomics complements current gene annotation strategies through the assessment of proteome profile similarity, protein covariation, and reverse proteome profiling. Thus, our study reveals principles that govern protein expression and provides a genome-spanning resource for functional annotation.

Natural proteome diversity links aneuploidy tolerance to protein turnover.

Accessing the natural genetic diversity of species unveils hidden genetic traits, clarifies gene functions and allows the generalizability of laboratory findings to be assessed. One notable discovery made in natural isolates of Saccharomyces cerevisiae is that aneuploidy-an imbalance in chromosome copy numbers-is frequent1,2 (around 20%), which seems to contradict the substantial fitness costs and transient nature of aneuploidy when it is engineered in the laboratory3-5. Here we generate a proteomic resource and merge it with genomic1 and transcriptomic6 data for 796 euploid and aneuploid natural isolates. We find that natural and lab-generated aneuploids differ specifically at the proteome. In lab-generated aneuploids, some proteins-especially subunits of protein complexes-show reduced expression, but the overall protein levels correspond to the aneuploid gene dosage. By contrast, in natural isolates, more than 70% of proteins encoded on aneuploid chromosomes are dosage compensated, and average protein levels are shifted towards the euploid state chromosome-wide. At the molecular level, we detect an induction of structural components of the proteasome, increased levels of ubiquitination, and reveal an interdependency of protein turnover rates and attenuation. Our study thus highlights the role of protein turnover in mediating aneuploidy tolerance, and shows the utility of exploiting the natural diversity of species to attain generalizable molecular insights into complex biological processes.

Distress in the care of people with chronic low back pain: insights from an ethnographic study.

Introduction: Distress is part of the experiences and care for people with chronic low back pain. However, distress is often pathologised and individualised; it is seen as a problem within the individual in pain and something to be downplayed, avoided, or fixed. To that end, we situate distress as a normal everyday relational experience circulating, affecting, moving in, through, and across bodies. Challenging practices that may amplify distress, we draw on the theorisation of affect as a relational assemblage to analyse physiotherapy clinical encounters in the care of people with chronic low back pain. Methods: Adopting a critical reflexive ethnographic approach, we analyse data from a qualitative project involving 15 ethnographic observations of patient-physiotherapist interactions and 6 collaborative dialogues between researchers and physiotherapists. We foreground conceptualisations of distress- and what they make (im)possible-to trace embodied assemblage formations and relationality when caring for people with chronic low back pain. Results: Our findings indicate that conceptualisation matters to the clinical entanglement, particularly how distress is recognised and navigated. Our study highlights how distress is both a lived experience and an affective relation-that both the physiotherapist and people with chronic low back pain experience distress and can be affected by and affect each other within clinical encounters. Discussion: Situated at the intersection of health sociology, sociology of emotions, and physiotherapy, our study offers a worked example of applying an affective assemblage theoretical framework to understanding emotionally imbued clinical interactions. Viewing physiotherapy care through an affective assemblage lens allows for recognising that life, pain, and distress are emerging, always in flux. Such an approach recognises that clinicians and patients experience distress; they are affected by and affect each other. It demands a more humanistic approach to care and helps move towards reconnecting the inseparable in clinical practice-emotion and reason, body and mind, carer and cared for.