Biology subjects

Gillet, L.

Publications and source records attributed to Gillet, L..

17 recordsLinked to original sources

bioRxiv2026

Weak interactions drive selective proteome demixing and tune the differential response to environmental perturbations

The intracellular space is a crowded environment where macromolecules perform distinct tasks despite pervasive "non-specific" interactions. Whether these interactions are functionally relevant and how they influence cellular organization remains unclear. Here, we developed QuPID-MS, which measures the propensity of proteins to phase separate in native cell extracts proteome-wide. We find that weak interactions drive condensation of half of the proteome in a crowding- and temperature-dependent manner and we present evidence that this proteome demixing occurs in cells. Importantly, protein condensation properties are conserved and broadly change when cells adapt to new environments, demonstrating that weak interactions are regulated and linked to function. Indeed, condensation of the growth regulator TORC1 coincides with its rapid inactivation, while high solubility of the stress-activated Hog1 ensures its activity across conditions. We thus uncover a fundamental organizing principle that allows tuning of cell growth to environmental fluctuations while ensuring other processes function robustly despite perturbations.

cell biology↗

bioRxiv2026

In-source fragmentation in mass spectrometry-based proteomics: prevalence, impact, and strategies for mitigation

Peptide-level analyses are becoming increasingly popular in mass spectrometry-based proteomics and are being applied, for example, in immunopeptidomics, structural proteomics, and analyses of post-translational modifications. In such analyses, peptides that are not biologically meaningful but instead arise as artifacts prior to mass spectrometry analysis pose the risk of data misinterpretation. Here, we describe an approach based on retention time analysis and precise chromatographic peak matching to identify peptides generated by in-source fragmentation (ISF), which occurs between chromatographic separation of peptide mixtures and the first mass filter of a tandem mass spectrometer (MS). To understand the prevalence and properties of ISF, we generated 13 proteomics datasets and analyzed them along with additional 25 previously published datasets spanning a broad range of sample types, MS, and proteomics approaches including classical bottom-up proteomics, immunopeptidomics, structural proteomics, and phosphoproteomics. We found that, in typical trypsin-digested samples on average 1 % of fully-tryptic peptides and 22 % of semi-tryptic peptides originated from ISF. However, we observed large variations between datasets, and in-source fragments exceeded, in some cases, a third of the total peptide identifications. The extent of ISF was dependent on the peptide sequence, the instrument, method parameters, and sample complexity. Although ISF did not impair relative quantification across samples, it generated peptides that could be misinterpreted qualitatively, inflated peptide identifications, and comprised up to 37 percent of peptides shorter than 9 amino acids in immunopeptidomics datasets. We propose that, for peptide-centric applications, our open-source ISF detection approach be used to re-annotate peptides generated by ISF and remove them to avoid misinterpretation of data. ISF is an increasing concern with improving mass spectrometers, as they enable detection of an ever-increasing number of m/z features, including low abundance features like ISF products. Our work thus addresses a growing issue in proteomics and presents solutions to mitigate the impact of in-source fragment peptides. In the future, improved feature detection algorithms may enable elucidation of new ISF patterns affecting side chains that have been missed so far, which could contribute to explaining the vast space of as-yet unannotated proteomics data.

biochemistry↗

bioRxiv2025

Systematic structural and functional analysis of metal-binding sites in native proteomes

Metal-binding proteins (MBPs) are widespread and critical for many biological processes. Proteomics-based approaches have identified MBPs in various systems but typically cannot determine the location of metal-binding sites or shed light on the functional roles of metals. Thus, a systems-wide map of metal binding sites and an understanding of the consequences of metal binding for protein function are still lacking. Here, we used limited proteolysis-coupled mass spectrometry (LiP-MS) combined with chelator treatment to globally map metal-protein interactions and binding sites in native protein lysates. We applied the pipeline, named Metal-LiP, to Escherichia coli, identified 981 peptides on 297 proteins that exhibited dose responsiveness to chelator treatment, and quantified the relative metal-binding affinity. These proteins are strongly enriched for known or predicted MBPs, based on our novel compiled ground truth dataset of previously annotated (n=1013) and predicted (n=850) MBPs. Further, chelator-responsive peptides mapped at or near annotated metal-binding sites in 3D protein structures, showing that Metal-LiP can identify metal-binding sites, and provided novel experimental evidence for previously predicted sites. Notably, Metal-LiP identified 225 novel candidate MBPs and we validated five of these novel MBPs (GatZ, AhpC, GrxB, MsrC, TrhO) using inductively coupled plasma-mass spectrometry to detect metal binding in purified proteins. Finally, we used orthogonal approaches to probe the broad functional consequences of metal binding. Using a combination of Metal-LiP, thermal proteome profiling, size-exclusion chromatography coupled to mass spectrometry, and structural analyses, we identified cases where metal binding affects protein stability, modulates the assembly states of protein complexes, or is likely to affect enzymatic activity. We thereby propose functional roles for metal binding in 98 of our Metal-LiP hits and in 225 proteins in total. In summary, we describe an approach to identify bona fide MBPs with binding site-level resolution across the proteome. We have combined it with other methods to identify 424 candidate MBPs in the E coli proteome, to map known and novel candidate metal-binding sites for 297 of these proteins, and to suggest functional roles of metal binding.

systems biology↗

bioRxiv2025

PKA regulates stress granule maturation to allow timely recovery after prolonged starvation

Cells have evolved multiple strategies to survive environmental stress conditions. This includes the formation of membrane-less cytoplasmic ribonucleoprotein structures called stress granules (SGs) that sequester and protect mRNAs encoding many housekeeping genes. SGs are not static biomolecular condensates but transform into solid states during a maturation phase. Although SG maturation is a hallmark of many neurodegenerative pathologies, little is known about the mechanisms and physiological relevance underlying the maturation process. Here we show that yeast SGs mature into a solid-like state during long-term stationary phase stress, which delays SG disassembly and cell cycle restart. Profiling of phosphorylation sites during stationary phase revealed that SG maturation is driven by protein kinase A (PKA)-dependent phosphorylation of the SG proteome. Indeed, upon stationary phase the catalytic PKA subunits condense in SGs where they maintain kinase activity, while during this time cytoplasmic PKA is inhibited. PKA-mediated phosphorylation of key SG components, like the pyruvate kinase Cdc19, is necessary and sufficient for its timely accumulation in SGs, where Cdc19 assembles into amyloid-like structures. Importantly, inhibiting PKA during long-term stationary phase prevents SG maturation, delaying ordered re-start of cell growth after re-feeding. Taken together, these results describe a SG maturation mechanism, selectively activated during chronic stress, that preserves SG integrity and promotes cell survival. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=164 HEIGHT=200 SRC="FIGDIR/small/663161v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@19c4d82org.highwire.dtl.DTLVardef@a4cf27org.highwire.dtl.DTLVardef@1c2577org.highwire.dtl.DTLVardef@1dfe84f_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIStress granules mature during chronic stress such as long-term stationary phase C_LIO_LIPhosphorylation of SG components by PKA is a hallmark of SG maturation C_LIO_LIPhosphorylation of Cdc19 by PKA promotes its maturation into an amyloid-like state C_LIO_LISG maturation acts as a timer for recovery after chronic stress C_LI

cell biology↗

bioRxiv2024

A deep learning-based multiscale integration of spatial omics with tumor morphology.

Spatial Transcriptomics (spTx) offers unprecedented insights into the spatial arrangement of the tumor microenvironment, tumor initiation/progression and identification of new therapeutic target candidates. However, spTx remains complex and unlikely to be routinely used in the near future. Hematoxylin and eosin (H&E) stained histological slides, on the other hand, are routinely generated for a large fraction of cancer patients. Here, we present a novel deep learning-based approach for multiscale integration of spTx with tumor morphology (MISO). We trained MISO to predict spTx from H&E on a new unpublished dataset of 72 10X Genomics Visium samples, and derived a novel estimate of the upper bound on the achievable performance. We demonstrate that MISO enables near single-cell-resolution, spatially-resolved gene expression prediction from H&E. In addition, MISO provides an effective patient representation framework that enables downstream predictive tasks such as molecular phenotyping or MSI prediction.

bioinformatics↗

bioRxiv2022

Large-scale changes of molecular network states explain complex traits

The complexity of many cellular and organismal traits results from poorly understood mechanisms integrating genetic and environmental factors via molecular networks. Here, we show when and how genetic perturbations lead to molecular changes that are confined to small parts of a network versus when they lead to large-scale adaptations of global network states. Integrating multi-omics profiling of genetically heterogeneous budding and fission yeast strains with an array of cellular traits identified a central state transition of the yeast molecular network that is related to PKA and TOR (PT) signaling. Genetic variants affecting this PT state globally shifted the molecular network along a single-dimensional axis, thereby modulating processes including energy- and amino acid metabolism, transcription, translation, cell cycle control and cellular stress response. We propose that genetic effects can propagate through large parts of molecular networks because of the functional requirement to centrally coordinate the activity of fundamental cellular processes. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/519111v1_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@18d3323org.highwire.dtl.DTLVardef@1185111org.highwire.dtl.DTLVardef@17238c7org.highwire.dtl.DTLVardef@1edc6e6_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract:C_FLOATNO Genetic variants directly or indirectly affecting the activity of PKA and/or TOR signaling cause global changes of transcriptomic and proteomic network states by modulating the activity of diverse cellular functions and network modules. Using marker genes acting downstream of PKA and TOR signaling we are able to quantify the activity status of combined PKA and TOR signaling (PT Score). This PT Score correlates with major transcriptomic and proteomic changes in response to genetic variability. Those large-scale molecular adaptations correlate with and explain phenotypic consequences for multiple cellular traits. Variants affecting the stoichiometry of proteins within a specific module have regional effects that remain confined to smaller parts of the molecular network. Variants affecting only one or very few proteins change molecular networks only locally. The global reorganization of network states caused by variants of the first type result in consequences for many cellular traits (i.e. pleiotropic effects), such as growth on different carbon sources, stress response, energy metabolism and replicative lifespan. (Created with BioRender.com) C_FIG

systems biology↗

bioRxiv2022

Meiotic Nuclear Pore Complex Remodeling Provides Key Insights into Nuclear Basket Organization

Nuclear pore complexes (NPCs) are large proteinaceous assemblies that mediate nuclear compartmentalization. NPCs undergo largescale structural rearrangements during mitosis in metazoans and some fungi. However, our understanding of NPC remodeling beyond mitosis remains limited. Using time-lapse fluorescence microscopy, we discovered that NPCs undergo two mechanistically-separable remodeling events during budding yeast meiosis whereby parts or all of the nuclear basket transiently dissociate from the NPC core during meiosis I and II, respectively. Meiosis I detachment, observed for Nup60 and Nup2, is driven by Polo kinase-mediated phosphorylation of Nup60 at its interface with the Y-complex. Subsequent reattachment of Nup60-Nup2 to the NPC core is mediated by a lipid-binding amphipathic helix in Nup60. Preventing Nup60-Nup2 reattachment causes misorganization of the entire nuclear basket in gametes. Strikingly, meiotic nuclear basket remodeling also occurs in the distantly related fission yeast, Schizosaccharomyces pombe. Our study reveals a conserved and developmentally programmed aspect of NPC plasticity, providing key mechanistic insights into nuclear basket organization. SUMMARYKing and Wettstein et al. reveal that nuclear pore complexes undergo two distinct remodeling events during budding yeast meiosis: partial and full nuclear basket detachment. By dissecting the regulation of these events, the study provides mechanistic insights into NPC organization.

cell biology↗

bioRxiv2021

A single oral immunization with a replication-competent adenovirus-vectored vaccine protects mice from influenza respiratory infection

The development of effective and flexible vaccine platforms is a major public health challenge as recently highlighted by the COVID-19 pandemic. Adenoviruses (AdVs) are easy to produce and have a good safety and efficacy profile when administered orally as demonstrated by the long-term use of oral AdV 4 and 7 vaccines in the US military. These viruses therefore appear to be the ideal backbone for the development of oral replicative vector vaccines. However, research on these vaccines is limited by the ineffective replication of human AdVs in laboratory animals. The use of mouse AdV type 1 (MAV-1) in its natural host allows infection to be studied under replicative conditions. Here, we orally vaccinated mice with MAV-1 vectors expressing the full length or the "headless" hemagglutinin (HA) of influenza to assess the protection conferred against an intranasal challenge of influenza. We showed that while the headless HA vector did not generate a significant humoral or cellular immune response to influenza, a single oral immunisation with the full-length HA vaccine generated influenza-specific and neutralizing antibodies and completely protected the mice against clinical signs and viral replication. ImportanceGiven the constant threat of pandemics and the need for annual vaccination against influenza and possibly emerging agents such as SARS-CoV-2, new types of vaccines that are easier to produce and administer and therefore more widely accepted are a critical public health need. Here, using a relevant animal model, we have shown that replicative oral AdV vaccine vectors can help make vaccination against major respiratory diseases more available, better accepted and therefore more effective. These results could be of major importance in the coming years in the fight against emerging diseases such as COVID-19.

microbiology↗

bioRxiv2021

Processing of the Ribosomal Ubiquitin-Like Fusion Protein FUBI-eS30/FAU is Required for 40S Maturation and Depends on USP36

In humans and other holozoan organisms, the ribosomal protein eS30 is synthesized as a fusion protein with the ubiquitin-like protein FUBI. However, FUBI is not part of the mature 40S ribosomal subunit and cleaved off by an as-of-yet unidentified protease. How FUBI-eS30 processing is coordinated with 40S subunit maturation is unknown. To study the mechanism and importance of FUBI-eS30 processing, we expressed non-cleavable mutants in human cells, which affected late steps of cytoplasmic 40S maturation, including the maturation of 18S rRNA and recycling of late-acting ribosome biogenesis factors. Differential affinity purification of wild-type and non-cleavable FUBI-eS30 mutants identified the deubiquitinase USP36 as a candidate FUBI-eS30 processing enzyme. Depletion of USP36 by RNAi or CRISPRi indeed impaired FUBI-eS30 processing and moreover, purified USP36 cut FUBI-eS30 in vitro. Together, these data demonstrate the functional importance of FUBI-eS30 cleavage and identify USP36 as a novel protease involved in this process.

cell biology↗

bioRxiv2019

Nα-terminal acetylation of proteins by NatA and NatB serves distinct physiological roles in Saccharomyces cerevisiae

SO_SCPLOWUMMARYC_SCPLOWN-terminal (Nt)-acetylation is a highly prevalent co-translational protein modification in eukaryotes, catalyzed by at least five Nt-acetyltransferases (Nat) with differing specificities. Nt-acetylation has been implicated in protein quality control but its broad biological significance remains elusive. We investigated the roles of the two major Nats of S. cerevisiae, NatA and NatB, by performing transcriptome, translatome and proteome profiling of natA{Delta} and natB{Delta} mutants. Our results do not support a general role of Nt-acetylation in protein degradation but reveal an unexpected range of Nat-specific phenotypes. NatA is implicated in systemic adaptation control, as natA{Delta} mutants display altered expression of transposons, sub-telomeric genes, pheromone response genes and nuclear genes encoding mitochondrial ribosomal proteins. NatB predominantly affects protein folding, as natB{Delta} mutants accumulate protein aggregates, induce stress responses and display reduced fitness in absence of the ribosome-associated chaperone Ssb. These phenotypic differences indicate that controlling Nat activities may serve to elicit distinct cellular responses.

molecular biology↗

bioRxiv2019

Integration of transcriptome, proteome and phosphoproteome data elucidates the genetic control of molecular networks

Genomic variation affects cellular networks by altering diverse molecular layers such as RNA levels, protein abundance, and post-translational protein modifications. However, it remains unclear how these different layers are affected by genetic polymorphisms and give rise to complex physiological phenotypes. To address these questions, we generated high-quality transcriptome, proteome, and phosphoproteome data for a panel of 112 genetically diverse yeast strains. While genetic effects on transcript abundances were generally transmitted to the protein level, we found a significant uncoupling of the transcript-protein relationship for certain protein classes, such as subunits of protein complexes. The additional phosphoproteomics data suggests that the same genetic locus often affects distinct sets of genes within each of these layers. In particular, QTLs tended to affect upstream regulatory proteins at the phosphorylation layer, whereas downstream pathway targets were typically affected at the transcript and protein abundance layers. Underscoring the importance of regulatory protein phosphorylation in linking genetic to phenotypic variation is the finding that the number of protein phosphosites associated with a given genetic locus was more predictive for its influence on cellular growth traits than the number of transcripts or proteins.\n\nThis study shows how multi-layered molecular networks mediate the effects of genomic variants to more complex physiological traits and highlights the important role of protein phosphorylation in mediating these effects.

systems biology↗

bioRxiv2019

High-throughput proteomic analysis of FFPE tissue samples facilitates tumor stratification

Formalin-fixed, paraffin-embedded (FFPE), biobanked tissue samples offer an invaluable resource for clinical and biomarker research. Here we developed a pressure cycling technology (PCT)-SWATH mass spectrometry workflow to analyze FFPE tissue proteomes and applied it to the stratification of prostate cancer (PCa) and diffuse large B-cell lymphoma (DLBCL) samples. We show that the proteome patterns of FFPE PCa tissue samples and their analogous fresh frozen (FF) counterparts have a high degree of similarity and we confirmed multiple proteins consistently regulated in PCa tissues in an independent sample cohort. We further demonstrate temporal stability of proteome patterns from FFPE samples that were stored between one to 15 years in a biobank and show a high degree of the proteome pattern similarity between two types histological region of small FFPE samples, i.e. punched tissue biopsies and thin tissue sections of micrometer thickness, despite the existence of certain degree of biological variations. Applying the method to two independent DLBCL cohorts we identified myeloperoxidase (MPO), a peroxidase enzyme, as a novel prognostic marker. In summary, this study presents a robust proteomic method to analyze bulk and biopsy FFPE tissues and reports the first systematic comparison of proteome maps generated from FFPE and FF samples. Our data demonstrate the practicality and superiority of FFPE over FF samples for proteome in biomarker discovery. Promising biomarker candidates for PCa and DLBCL have been discovered.

biochemistry↗

bioRxiv2019

A distinct pool of Nav1.5 channels at the lateral membrane of murine ventricular cardiomyocytes

BackgroundIn cardiac ventricular muscle cells, the presence of voltage-gated sodium channels Nav1.5 at the lateral membrane depends in part on the interaction between the dystrophin-syntrophin complex and the Nav1.5 C-terminal PDZ-domain-binding sequence Ser-Ile-Val (SIV motif). 1-Syntrophin, a PDZ-domain adaptor protein, mediates the interaction between Nav1.5 and dystrophin at the lateral membrane of cardiac cells. Using the cell-attached patch-clamp approach on cardiomyocytes expressing Nav1.5 in which the SIV motif is deleted ({Delta}SIV), sodium current (INa) recordings from the lateral membrane revealed an SIV-motif-independent INa. Since immunostainings have suggested that Nav1.5 is expressed in transverse (T-) tubules, this remaining INa might be conducted by channels in the T-tubules. Of note, a recent study using heterologous expression systems showed that 1-syntrophin also interacts with the Nav1.5 N-terminus, which may explain the SIV-motif independent INa at the lateral membrane of cardiomyocytes.\n\nAimTo address the role of 1-syntrophin in regulating the INa at the lateral membrane of cardiac cells.\n\nMethods and resultsPatch-clamp experiments in cell-attached configuration were performed on the lateral membranes of wild-type, 1-syntrophin knock-down, and {Delta}SIV ventricular mouse cardiomyocytes. Compared to wild-type, a reduction of the lateral INa was observed in myocytes from 1-syntrophin knockdown hearts. However, similar to {Delta}SIV myocytes, a remaining INa was still recorded. In addition, cell-attached INa recordings from lateral membrane did not differ significantly between non-detubulated and detubulated {Delta}SIV cardiomyocytes. Lastly, we obtained evidence suggesting that cell-attached patch-clamp experiments on the lateral membrane cannot record currents conducted by channels in T-tubules such as calcium channels.\n\nConclusionAltogether, these results suggest the presence of a sub-pool of sodium channels at the lateral membrane of cardiomyocytes that is independent of 1-syntrophin and the PDZ-binding motif of Na 1.5, located in membrane domains outside of T-tubules. The question of a T-tubular pool of Nav1.5 channels however remains open.

physiology↗

bioRxiv2019

Dystrophin and calcium current are decreased in cardiomyocytes expressing Cre enzyme driven by αMHC but not TNT promoter

BackgroundThe Cre/lox system is a potent technology to control gene expression in mouse tissues. However, cardiac alterations following cardiac-specific Cre enzyme expression in non-loxP-flanked genome heart have been reported. Recently, many loxP like sites have been identified in the wild-type mouse genome. Interestingly one of them is localized in the Dmd gene encoding the dystrophin protein known to be crucial for stabilization of cardiac voltage-gated ion channels Nav1.5 and Cav1.2. AimHere, we studied the potential alteration of dystrophin expression in adult alpha-myosin heavy chain (MHC)-Cre mice, which are extensively used for cardiac-specific recombination, and investigated Troponin T (TNT)-Cre mice as a potential alternative. MethodsCardiac-specific MHC-Cre and TNT-Cre mouse lines expressing Cre recombinase under the control of the cardiac-specific alpha-myosin-heavy chain, and rat cardiac troponin T2 promoter respectively were used. Western blots, quantitative RT-PCR, immunostainings, and patch-clamp experiments were performed to characterize MHC-Cre and TNT-Cre mouse hearts and cardiomyocytes. ResultsDystrophin protein level was decreased in hearts from 12-week-old MHC-Cre+ mice compared to MHC-Cre-. Reduction of dystrophin was more pronounced with age. No significant difference was observed between 8-week-old MHC-Cre+ mice and MHC-Cre-. Immunostainings performed on cardiac sections showed reduced dystrophin signal at the lateral membrane of MHC-Cre+ cardiomyocytes. Quantitative RT-PCR showed decreased mRNA levels of Dmd gene encoding dystrophin. Finally, patch-clamp experiments showed a significant decrease in calcium current (ICaL) in adult MHC-Cre+ cardiomyocytes compared to MHC-Cre-. Neither dystrophin nor ICaL was reduced in adult TNT-Cre+ mouse hearts compared to TNT-Cre-. ConclusionIn contrary to TNT-Cre+ mice, the sole expression of Cre recombinase can alter the cardiac phenotype of MHC-Cre+ mice. Thus, researchers should include the "Cre-only" condition as control condition when designing experiments with Cre mouse strains.

physiology↗

bioRxiv2018

The GTPase Nog1 couples polypeptide exit tunnel quality control with ribosomal stalk assembly

Eukaryotic ribosome precursors acquire translation competence in the cytoplasm through stepwise release of bound assembly factors, and proofreading of their functional centers. In case of the large subunit precursor (pre-60S), these essential steps include eviction of placeholders Arx1 and Mrt4 that prevent premature loading of the protein-folding machinery at the polypeptide exit tunnel (PET), and the ribosomal stalk, respectively. Here, we reveal that sequential ATPase and GTPase activities license release factors Rei1 and Yvh1 recruitment to the pre-60S in order to trigger Arx1 and Mrt4 removal. Drg1-ATPase activity extracts the C-terminal tail of Nog1 from the PET, enabling Rei1 to probe PET integrity, and then catalyze Arx1 release. Subsequently, GTPase hydrolysis stimulates Nog1 removal from the pre-60S, permitting Yvh1 to mediate Mrt4 release, and initiate ribosomal stalk assembly. Thus, Nog1 couples quality control and assembly of spatially distant functional centers during ribosome formation.

biochemistry↗

bioRxiv2018

Survival cost to relocation does not reduce population self-sustainability in an amphibian

O_LIRelocations are increasingly popular among wildlife managers despite sharp debate and low rate of relocation success in vertebrates. In this context, understanding the influence of extrinsic (e.g., relocation design, habitat characteristics) and intrinsic factors (e.g., age and sex) on demographic parameters such as survival that regulate the dynamics of relocated populations is critical to improve relocation protocols and better predict relocation success.\nC_LIO_LIWe investigated survival in naturally established and relocated populations of yellow-bellied toads (Bombina variegata), an amphibian that was nearly extinct in Belgium by the late 1990s. We quantified survival at three ontogenetic stages (juvenile, subadult, and adult) in the relocated population, the source population, and a control population. In the relocated population, we quantified survival in captive bred individuals and their locally born descendants.\nC_LIO_LIWe showed that survival at juvenile and subadult stages was relatively similar in all populations. In contrast, relocated adult survival was lower than adult survival in the source and control populations. Despite this, offspring of relocated animals (the next generation, regardless of life stage) survived at similar rates to offspring in the source and control populations. Our simulations revealed that the relocated population was self-sustaining under different scenarios and that the fate (e.g., stability or finite rate of increase) of the simulated populations was highly dependent on the fecundity of relocated adults and their offspring.\nC_LIO_LIPolicy implications. Our results indicate that survival in relocated individuals is lower than in non-relocated individuals but that this cost (= reduced survival) disappears in the second generation. A finer understanding of how relocation affects demographic processes is an important step in improving relocation success of amphibians and other animals.\nC_LI

ecology↗

bioRxiv2018

Rapid proteotyping reveals cancer biology and drug response determinants in the NCI-60 cells

We describe the rapid and reproducible acquisition of quantitative proteome maps for the NCI-60 cancer cell lines and their use to reveal cancer biology and drug response determinants. Proteome datasets for the 60 cell lines were acquired in duplicate within 30 working days using pressure cycling technology and SWATH mass spectrometry. We consistently quantified 3,171 proteotypic proteins annotated in the SwissProt database across all cell lines, generating a data matrix with 0.1% missing values, allowing analyses of protein complexes and pathway activities across all the cancer cells. Systematic and integrative analysis of the genetic variation, mRNA expression and proteomic data of the NCI-60 cancer cell lines uncovered complementarity between different types of molecular data in the prediction of the response to 240 drugs. We additionally identified novel proteomic drug response determinants for clinically relevant chemotherapeutic and targeted therapies. We anticipate that this study represents a significant advance toward the translational application of proteotypes, which reveal biological insights that are easily missed in the absence of proteomic data.

systems biology↗