Active learning for medical image segmentation with stochastic batches

The performance of learning-based algorithms improves with the amount of labelled data used for training. Yet, manually annotating data is particularly difficult for medical image segmentation tasks because of the limited expert availability and intensive manual effort required. To reduce manual labelling, active learning (AL) targets the most informative samples from the unlabelled set to annotate and add to the labelled training set. On the one hand, most active learning works have focused on the classification or limited segmentation of natural images, despite active learning being highly desirable in the difficult task of medical image segmentation. On the other hand, uncertainty-based AL approaches notoriously offer sub-optimal batch-query strategies, while diversity-based methods tend to be computationally expensive. Over and above methodological hurdles, random sampling has proven an extremely difficult baseline to outperform when varying learning and sampling conditions. This work aims to take advantage of the diversity and speed offered by random sampling to improve the selection of uncertainty-based AL methods for segmenting medical images. More specifically, we propose to compute uncertainty at the level of batches instead of samples through an original use of stochastic batches (SB) during sampling in AL. Stochastic batch querying is a simple and effective add-on that can be used on top of any uncertainty-based metric. Extensive experiments on two medical image segmentation datasets show that our strategy consistently improves conventional uncertainty-based sampling methods. Our method can hence act as a strong baseline for medical image segmentation. The code is available on: https://github.com/Minimel/StochasticBatchAL.git.Comment: Accepted to Medical Image Analysis, 17 page

HECATE factors control cell fate transitions and organ patterning in Arabidopsis thaliana

Throughout their life span, plants keep the ability to generate new tissues and organs. This remarkable developmental property relies on the continuous activity of pluripotent stem cells localized in meristems, which generate cell progenies acquiring specific cellular identities. Thus, the regulatory processes controlling the progression of stem cell lineages and their final differentiation are essential to establish the whole body plan and to ultimately define plant reproductive success. The integration of phytohormonal signals like auxin or cytokinin with key transcriptional regulators is central for balancing stem cell activity and differentiation (reviewed in Gaillochet and Lohmann, 2015), however our current understanding of the regulatory interactions mediating this molecular communication remains elusive. In this study, we used an integrated approach–including live-cell imaging, computational modeling, genome-wide profiling and genetic functional characterization–to investigate the function of the bHLH transcription factors HECATE (HEC) in controlling stem cell homeostasis and organ patterning. We found that HEC regulatory function is highly versatile and tightly interacts with cytokinin and auxin signalling pathways under multiple developmental contexts. We show in the shoot apical meristem that HEC function regulates the timing of stem cell differentiation by locally promoting cytokinin at the centre of the meristem and repressing auxin signals at the periphery. In contrast, we found that HEC genes pattern style differentiation at the gynoecium by regulating auxin flow and by buffering cytokinin responses. Using a gene network reconstruction approach, we started to unravel the regulatory interactions mediating HEC functional versatility and identified NGATHA transcription factors as relevant direct targets controlling shoot meristem activity. Together, our findings refine the molecular and developmental framework for shoot meristem activity and gynoecium differentiation

A Comprehensive Toolkit for Inducible, Cell Type-Specific Gene Expression in Arabidopsis.

Understanding the context-specific role of gene function is a key objective of modern biology. To this end, we generated a resource for inducible cell type-specific transactivation in Arabidopsis ( <i>Arabidopsis thaliana</i> ) based on the well-established combination of the chimeric GR-LhG4 transcription factor and the synthetic <i>pOp</i> promoter. Harnessing the flexibility of the GreenGate cloning system, we produced a comprehensive set of transgenic lines termed GR-LhG4 driver lines targeting most tissues in the Arabidopsis shoot and root with a strong focus on the indeterminate meristems. When we combined these transgenic lines with effectors under the control of the <i>pOp</i> promoter, we observed tight temporal and spatial control of gene expression. In particular, inducible expression in F1 plants obtained from crosses of driver and effector lines allows for rapid assessment of the cell type-specific impact of an effector with high temporal resolution. Thus, our comprehensive and flexible method is suitable for overcoming the limitations of ubiquitous genetic approaches, the outputs of which often are difficult to interpret due to the widespread existence of compensatory mechanisms and the integration of diverging effects in different cell types

HY5 and phytochrome activity modulate shoot to root coordination during thermomorphogenesis.

This is the author accepted manuscript. The final version is available from The Company of Biologists via the DOI in this record Temperature is one of the most impactful environmental factors to which plants adjust their growth and development. While the regulation of temperature signaling has been extensively investigated for the aerial part of plants, much less is known and understood about how roots sense and modulate their growth in response to fluctuating temperatures. Here we found that shoot and root growth responses to high ambient temperature are coordinated during early seedling development. A shoot signaling module that includes HY5, the phytochromes and the PIFs exerts a central function in coupling these growth responses and maintain auxin levels in the root. In addition to the HY5/PIF-dependent shoot module, a regulatory axis composed of auxin biosynthesis and auxin perception factors controls root responses to high ambient temperature. Together, our findings show that shoot and root developmental responses to temperature are tightly coupled during thermomorphogenesis and suggest that roots integrate energy signals with local hormonal inputs.National Institute of General Medical Sciences of the National Institutes of Healt

The receptor kinase SRF3 coordinates iron- level and flagellin dependent defense and growth responses in plants

Iron is critical for host–pathogen interactions. While pathogens seek to scavenge iron to spread, the host aims at decreasing iron availability to reduce pathogen virulence. Thus, iron sensing and homeostasis are of particular importance to prevent host infection and part of nutritional immunity. While the link between iron homeostasis and immunity pathways is well established in plants, how iron levels are sensed and integrated with immune response pathways remains unknown. Here we report a receptor kinase SRF3, with a role in coordinating root growth, iron homeostasis and immunity pathways via regulation of callose synthases. These processes are modulated by iron levels and rely on SRF3 extracellular and kinase domains which tune its accumulation and partitioning at the cell surface. Mimicking bacterial elicitation with the flagellin peptide flg22 phenocopies SRF3 regulation upon low iron levels and subsequent SRF3-dependent responses. We propose that SRF3 is part of nutritional immunity responses involved in sensing external iron levels

Separate elements of the TERMINAL FLOWER 1 cis-regulatory region integrate pathways to control flowering time and shoot meristem identity

TERMINAL FLOWER 1 (TFL1) is a key regulator of Arabidopsis plant architecture that responds to developmental and environmental signals to control flowering time and the fate of shoot meristems. TFL1 expression is dynamic, being found in all shoot meristems, but not in floral meristems, with the level and distribution changing throughout development. Using a variety of experimental approaches we have analysed the TFL1 promoter to elucidate its functional structure. TFL1 expression is based on distinct cis-regulatory regions, the most important being located 3' of the coding sequence. Our results indicate that TFL1 expression in the shoot apical versus lateral inflorescence meristems is controlled through distinct cis-regulatory elements, suggesting that different signals control expression in these meristem types. Moreover, we identified a cis-regulatory region necessary for TFL1 expression in the vegetative shoot and required for a wild-type flowering time, supporting that TFL1 expression in the vegetative meristem controls flowering time. Our study provides a model for the functional organisation of TFL1 cis-regulatory regions, contributing to our understanding of how developmental pathways are integrated at the genomic level of a key regulator to control plant architecture.This work was supported by a Joint Project Grant from the Royal Society [ESEP/JP 15057] to D.B. and F.M. The laboratory of F.M. was funded by grants from the Spanish Ministerio de Ciencia e Innovacion [BIO2009-10876 and CSD2007-00057], the Spanish Ministerio de Economia y Competitividad [BFU2012-38929] and from the Generalitat Valenciana [ACOMP09-083 and ACOMP2012-099]. Work in the Y.H. lab was supported by the Plant Genome Research Program from the National Science Foundation [NSF-PGRP-IOS-1339388]. P.F.-N. was supported by a fellowship from the I3P Program of Consejo Superior de Investigaciones Cientificas.Serrano Mislata, A.; Fernández Nohales, P.; Domenech-Benlloch, MJ.; Hanzawa, Y.; Bradley, DJ.; Madueño Albi, F. (2016). Separate elements of the TERMINAL FLOWER 1 cis-regulatory region integrate pathways to control flowering time and shoot meristem identity. Development. 143(18):3315-3327. https://doi.org/10.1242/dev.135269S331533271431