scholarly journals Three million images and morphological profiles of cells treated with matched chemical and genetic perturbations

2022 ◽  
Author(s):  
Srinivas Niranj Chandrasekaran ◽  
Beth A. Cimini ◽  
Amy Goodale ◽  
Lisa Miller ◽  
Maria Kost-Alimova ◽  
...  

We present a new, carefully designed and well-annotated dataset of images and image-based profiles of cells that have been treated with chemical compounds and genetic perturbations. Each gene that is perturbed is a known target of at least two compounds in the dataset. The dataset can thus serve as a benchmark to evaluate methods for predicting similarities between compounds and between genes and compounds, measuring the effect size of a perturbation, and more generally, learning effective representations for measuring cellular state from microscopy images. Advancements in these applications can accelerate the development of new medicines.

2016 ◽  
Author(s):  
Mark-Anthony Bray ◽  
Shantanu Singh ◽  
Han Han ◽  
Chadwick T. Davis ◽  
Blake Borgeson ◽  
...  

AbstractIn morphological profiling, quantitative data are extracted from microscopy images of cells to identify biologically relevant similarities and differences among samples based on these profiles. This protocol describes the design and execution of experiments using Cell Painting, a morphological profiling assay multiplexing six fluorescent dyes imaged in five channels, to reveal eight broadly relevant cellular components or organelles. Automated image analysis software identifies individual cells and measures ~1,500 morphological features (various measures of size, shape, texture, intensity, etc.) to produce a rich profile suitable for detecting subtle phenotypes. Profiles of cell populations treated with different experimental perturbations can be compared to suit many goals, such as identifying the phenotypic impact of chemical or genetic perturbations, grouping compounds and/or genes into functional pathways, and identifying signatures of disease. Cell culture and image acquisition takes 2 weeks; feature extraction and data analysis take an additional 1-2 weeks.


Author(s):  
R. Courtoy ◽  
L.J. Simar ◽  
J. Christophe

Several chemical compounds induce amine liberation from mast cells but do not necessarily provoque the granule expulsion. For example, poly-dl-lysine induces modifications of the cellular membrane permeability which promotes ion exchange at the level of mast cell granules. Few of them are expulsed but the majority remains in the cytoplasm and appears less dense to the electrons. A cytochemical analysis has been performed to determine the composition of these granules after the polylysine action.We have previously reported that it was possible to demonstrate polyanions on epon thin sections using a cetylpyridinium ferric thiocyanate method. Organic bases are selectively stained with cobalt thiocyanate and the sulfhydryle groups are characterized with a silver methenamine reaction. These techniques permit to reveal the mast cell granule constituents, i.e. heparin, biogenic amines and basic proteins.


Author(s):  
J. Temple Black ◽  
Jose Guerrero

In the SEM, contrast in the image is the result of variations in the volume secondary electron emission and backscatter emission which reaches the detector and serves to intensity modulate the signal for the CRT's. This emission is a function of the accelerating potential, material density, chemistry, crystallography, local charge effects, surface morphology and especially the angle of the incident electron beam with the particular surface site. Aside from the influence of object inclination, the surface morphology is the most important feature In producing contrast. “Specimen collection“ is the name given the shielding of the collector by adjacent parts of the specimen, producing much image contrast. This type of contrast can occur for both secondary and backscatter electrons even though the secondary electrons take curved paths to the detector-collector.Figure 1 demonstrates, in a unique and striking fashion, the specimen collection effect. The subject material here is Armco Iron, 99.85% purity, which was spark machined.


Author(s):  
E. I. Alessandrini ◽  
M. O. Aboelfotoh

Considerable interest has been generated in solid state reactions between thin films of near noble metals and silicon. These metals deposited on Si form numerous stable chemical compounds at low temperatures and have found applications as Schottky barrier contacts to silicon in VLSI devices. Since the very first phase that nucleates in contact with Si determines the barrier properties, the purpose of our study was to investigate the silicide formation of the near noble metals, Pd and Pt, at very thin thickness of the metal films on amorphous silicon.Films of Pd and Pt in the thickness range of 0.5nm to 20nm were made by room temperature evaporation on 40nm thick amorphous Si films, which were first deposited on 30nm thick amorphous Si3N4 membranes in a window configuration. The deposition rate was 0.1 to 0.5nm/sec and the pressure during deposition was 3 x 10 -7 Torr. The samples were annealed at temperatures in the range from 200° to 650°C in a furnace with helium purified by hot (950°C) Ti particles. Transmission electron microscopy and diffraction techniques were used to evaluate changes in structure and morphology of the phases formed as a function of metal thickness and annealing temperature.


Author(s):  
R. Levi-Setti ◽  
J.M. Chabala ◽  
Y.L. Wang

Finely focused beams extracted from liquid metal ion sources (LMIS) provide a wealth of secondary signals which can be exploited to create high resolution images by the scanning method. The images of scanning ion microscopy (SIM) encompass a variety of contrast mechanisms which we classify into two broad categories: a) Emission contrast and b) Analytical contrast.Emission contrast refers to those mechanisms inherent to the emission of secondaries by solids under ion bombardment. The contrast-carrying signals consist of ion-induced secondary electrons (ISE) and secondary ions (ISI). Both signals exhibit i) topographic emission contrast due to the existence of differential geometric emission and collection effects, ii) crystallographic emission contrast, due to primary ion channeling phenomena and differential oxidation of crystalline surfaces, iii) chemical emission or Z-contrast, related to the dependence of the secondary emission yields on the Z and surface chemical state of the target.


Author(s):  
P. Moine ◽  
G. M. Michal ◽  
R. Sinclair

Premartensitic effects in near equiatomic TiNi have been pointed out by several authors(1-5). These include anomalous contrast in electron microscopy images (mottling, striations, etc. ),diffraction effects(diffuse streaks, extra reflections, etc.), a resistivity peak above Ms (temperature at which a perceptible amount of martensite is formed without applied stress). However the structural changes occuring in this temperature range are not well understood. The purpose of this study is to clarify these phenomena.


2000 ◽  
Vol 8 (1) ◽  
pp. 18-24 ◽  
Author(s):  
Gert Kaluza ◽  
Hans-Henning Schulze

Zusammenfassung. Die Evaluation von Interventionen zur Prävention und Gesundheitsförderung stellt ein zentrales Aufgabenfeld der gesundheitspsychologischen Forschung dar. Häufige methodische Probleme entsprechender Evaluationsstudien betreffen 1. Ausgangswert-Unterschiede bei nicht randomisierten Studiendesigns, 2. Abhängigkeit von Beobachtungen bei Gruppeninterventionsstudien, 3. Kapitalisierung von Irrtumswahrscheinlichkeiten aufgrund einer Vielzahl von abhängigen Variablen und 4. Beurteilung der praktischen Relevanz statistisch signifikanter Interventionseffekte. Zu deren pragmatischer Lösung werden u.a. 1. die Anwendung kovarianzanalytischer Auswertungsstrategien, 2. die Berechnung von Intraclass-Korrelationen und ggf. eine Datenauswertung auf der Ebene der Gruppenmittelwerte, 3. eine Reduktion der Anzahl der abhängigen Variablen mittels Hauptkomponentenanalyse sowie eine Alpha-Adjustierung unter Berücksichtigung der Teststärke (“compromise power analysis”) und 4. die Umrechnung gängiger Effektstärken in prozentuale Erfolgsraten (“binomial effect size display”) empfohlen.


2006 ◽  
Vol 20 (3) ◽  
pp. 186-194 ◽  
Author(s):  
Susanne Mayr ◽  
Michael Niedeggen ◽  
Axel Buchner ◽  
Guido Orgs

Responding to a stimulus that had to be ignored previously is usually slowed-down (negative priming effect). This study investigates the reaction time and ERP effects of the negative priming phenomenon in the auditory domain. Thirty participants had to categorize sounds as musical instruments or animal voices. Reaction times were slowed-down in the negative priming condition relative to two control conditions. This effect was stronger for slow reactions (above intraindividual median) than for fast reactions (below intraindividual median). ERP analysis revealed a parietally located negativity of the negative priming condition compared to the control conditions between 550-730 ms poststimulus. This replicates the findings of Mayr, Niedeggen, Buchner, and Pietrowsky (2003) . The ERP correlate was more pronounced for slow trials (above intraindividual median) than for fast trials (below intraindividual median). The dependency of the negative priming effect size on the reaction time level found in the reaction time analysis as well as in the ERP analysis is consistent with both the inhibition as well as the episodic retrieval account of negative priming. A methodological artifact explanation of this effect-size dependency is discussed and discarded.


Methodology ◽  
2019 ◽  
Vol 15 (3) ◽  
pp. 97-105
Author(s):  
Rodrigo Ferrer ◽  
Antonio Pardo

Abstract. In a recent paper, Ferrer and Pardo (2014) tested several distribution-based methods designed to assess when test scores obtained before and after an intervention reflect a statistically reliable change. However, we still do not know how these methods perform from the point of view of false negatives. For this purpose, we have simulated change scenarios (different effect sizes in a pre-post-test design) with distributions of different shapes and with different sample sizes. For each simulated scenario, we generated 1,000 samples. In each sample, we recorded the false-negative rate of the five distribution-based methods with the best performance from the point of view of the false positives. Our results have revealed unacceptable rates of false negatives even with effects of very large size, starting from 31.8% in an optimistic scenario (effect size of 2.0 and a normal distribution) to 99.9% in the worst scenario (effect size of 0.2 and a highly skewed distribution). Therefore, our results suggest that the widely used distribution-based methods must be applied with caution in a clinical context, because they need huge effect sizes to detect a true change. However, we made some considerations regarding the effect size and the cut-off points commonly used which allow us to be more precise in our estimates.


2019 ◽  
Vol 227 (4) ◽  
pp. 261-279 ◽  
Author(s):  
Frank Renkewitz ◽  
Melanie Keiner

Abstract. Publication biases and questionable research practices are assumed to be two of the main causes of low replication rates. Both of these problems lead to severely inflated effect size estimates in meta-analyses. Methodologists have proposed a number of statistical tools to detect such bias in meta-analytic results. We present an evaluation of the performance of six of these tools. To assess the Type I error rate and the statistical power of these methods, we simulated a large variety of literatures that differed with regard to true effect size, heterogeneity, number of available primary studies, and sample sizes of these primary studies; furthermore, simulated studies were subjected to different degrees of publication bias. Our results show that across all simulated conditions, no method consistently outperformed the others. Additionally, all methods performed poorly when true effect sizes were heterogeneous or primary studies had a small chance of being published, irrespective of their results. This suggests that in many actual meta-analyses in psychology, bias will remain undiscovered no matter which detection method is used.


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