Biology subjects

Iyer, A.

Publications and source records attributed to Iyer, A..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Salience Network Segregation and Symptom Profiles in Psychosis Prodrome Subgroups

BackgroundUnderstanding neurobiological similarities between individuals with prodromal psychosis symptoms can improve early identification and intervention strategies. Here, we aimed to (i) identify neurobiologically similar groups by integrating resting-state functional connectivity and prodromal symptom data and (ii) discern discriminating symptom profiles and brain connectivity patterns in the identified sub-groups. MethodsOur sample (N=922) was extracted from the Philadelphia Neurodevelopmental Cohort and included individuals ages 12-21 years with fMRI and self-reported psychopathology data. Analyses were conducted separately for youth and early adults. We first constructed a two-layer network using pair-wise similarity distances between participants based on resting-state functional connectivity and prodromal positive psychosis symptoms. We then performed community detection via a multiplex stochastic block model to identify subject clusters. ResultsWe identified 2 blocks or communities for both the youth (n=458 and 179) and early adult (n=173 and 112) groups. Connection parameter estimates of the neuroimaging layer were nearly identical between blocks for both age groups whereas there was significant variation for the symptom layer. Psychopathology symptom and brain system segregation profiles were consistent across age groups. The youth block (n=458) with higher salience network segregation values had higher mean scores for prodromal symptoms. However, the early adult block (n=173) with lower salience network segregation had higher mean prodromal scores. ConclusionsBy integrating global similarities in brain connectivity and prodromal symptoms, we identified distinct subgroups. These groups show differences in symptom profiles and network segregation in youth and early adults, indicating significant variations in developmental paths for psychosis spectrum.

neuroscience↗

bioRxiv2024

Axenisation of oleaginous microalgal cultures via anoxic photosensitisation.

Growing interest in sustainable biofuel research has necessitated high quality axenic oleaginous microalgal strains. Unfortunately, most strains available in culture banks contain commensal microbes such as bacteria and the default decontamination method involves antibiotic treatment which has begun to exacerbate the emergence of antibiotic resistance. To overcome this problem, anoxic photosensitisation was investigated as an alternate approach. Four oleaginous microalgal species (Tetradesmus obliquus, Desmodesmus armatus, Chlorella vulgaris and Nannochloropsis limnetica) were incubated in varying concentrations of Rose Bengal (0 {micro}M, 1 {micro}M, 3 {micro}M and 9 {micro}M) either in normal (oxic) or anoxic conditions, for 72 h under light (8.85 {+/-} 0.40 W m-2) in a specially designed heterotrophic growth complex (HGC) medium, followed by 72 h in standard Bolds Basal Medium (BBM). Commonly used antibiotics-based protocol was used as the control method. Post treatment, cell numbers and percentage populations were counted with Flow cytometry, and viability was tested using standard plating methods using BBM and LB. Additionally, the contaminating microbes in the cultures were profiled using 16s rRNA sequencing. Anoxic conditions were able to significantly decrease bacterial content, albeit with an equally detrimental effect on the microalgal population. Although the responses differed between the microalgae, anoxic incubation along with Rose Bengal at 3 {micro}M was able to completely decontaminate N. limnetica and C. vulgaris, while D. armatus and T. obliquus could be decontaminated with an additional streak-plating step. None of the cultures could be decontaminated using antibiotics treatment owing to the presence of gram-negative, multi-drug resistant bacteria such as S. maltophilia, M. foliorum and S. chilensis. These results suggest that decontamination of xenic microalgal cultures was largely due to anoxy, that was synergistically enhanced by Rose Bengal at a concentration of [≥]3 {micro}M. HighlightsO_LIRose Bengal at 3 {micro}M in anoxic conditions can help achieve axenic microalgal cultures. C_LIO_LIStandard antibiotics were unable to decontaminate any of the cultures owing to the presence of multi-drug resistant bacteria. C_LIO_LIStandard antibiotics treatment was deleterious to D. armatus cultures. C_LIO_LIStreak plating may be required for D. armatus and T. obliquus after anoxic Rose Bengal treatment to obtain individual colonies for further inoculation. C_LI

microbiology↗

bioRxiv2024

Inheritable cell-states shape drug-persister correlations and population dynamics in cancer cells

Drug tolerant persisters (DTPs) drive cancer therapy resistance by temporarily evading drug action, allowing multiple routes to eventual permanent resistance. Despite clear evidence for DTPs, the timing of their emergence, proliferative nature, and how their population dynamics arise from measured single-cell kinetics remain poorly understood. Here we use time-lapse microscopy data from two cancer cell lines, integrating single-cell and population measurements, to develop a quantitative description of drug persistence. Contrary to the expectation that increasing levels of genotoxic stress should lead to slower times to division and faster times to death, we observe minor changes in the single-cell intermitotic and death time distributions upon increasing cisplatin concentration. Yet, population decay rates increase 3-fold, suggesting a surprising independence of the overall dynamics from the measured birth and death rates. To explain this phenomenon, we argue that the observed lineage correlations and concentration-dependent decay rates imply cell-state dependent fate choices made both pre and post-cisplatin as opposed to just post-drug birth/death rate-based competitive fate choices. We demonstrate that these cell-states, present in the ancestors of DTP and sensitive cells, exhibit no difference in cycling speed and are inherited across 2-3 cellular generations. A stochastic model implementing these rules simultaneously recapitulates the observed decay rates and cell-fate correlations, also explaining how pre-drug fate decisions are consistent with barcoding experiments where barcode diversity remains unchanged after drug administration. Our results provide a powerful perspective on drug tolerance based on general arguments, without requiring knowledge of the underlying molecular architecture of the heterogeneous cell states.

cancer biology↗

bioRxiv2024

GSEA and co-expression network approach to identify molecular processes affected in Porto-sinusoidal Vascular Disease

11.1 BackgroundPorto-sinusoidal vascular disease (PSVD) is a complex, rare liver disease characterized by the absence of cirrhosis, with or without the presence of portal hypertension or histological lesions. Given the knowledge gaps in the mechanisms involved in this disease with unknown etiology, we used omics-based approaches to further elucidate the pathways affected by PSVD, facilitating improvements in the prognosis, diagnosis, and treatment options for these patients. 1.2 MethodsWe applied gene set enrichment analysis (GSEA) and weighted gene coexpression network analysis (WGCNA) to identify pathways dysregulated in PSVD. Network construction and visualization were performed in Cytoscape to explore interconnectivity among enriched processes. Within key modules, candidate genes were prioritized by ranking approaches and cross-referenced with findings from previous studies. 1.3 Results and ConclusionThis study revealed that PSVD is characterized by coordinated dysregulation, with immune and signaling pathways activated alongside the suppression of metabolic, ribosomal, and mitochondrial programs. Alterations in ribosomal proteins, ATP synthase subunits, and serpin family members highlight translational, bioenergetic, and anticoagulant dysfunction as core mechanisms. Together, these findings define PSVD as a disorder of integrated immune, vascular, and metabolic imbalance.

bioinformatics↗

bioRxiv2024

LHX2 regulates dendritic morphogenesis in layer II/III of the neocortex via distinct pathways in progenitors and postmitotic neurons.

In the mammalian neocortex, excitatory neurons that send projections via the corpus callosum are critical to integrating information across the two brain hemispheres. The molecular mechanisms governing the development of the dendritic arbours and spines of these callosal neurons are poorly understood, yet these features are critical to their physiological properties. LIM Homeodomain 2 (Lhx2), a regulator of fundamental processes in cortical development, is expressed in postmitotic callosal neurons occupying layer II/III of the neocortex and also in their progenitors residing in the embryonic day (E) 15.5 ventricular zone of the mouse neocortex. We tested whether this factor is essential for dendritic arbour configuration and spine morphogenesis of layer II/III neurons. Here, we report loss of Lhx2, either in postmitotic layer II/III neurons or their progenitors, resulted in shrunken dendritic arbours and perturbed spine morphology. The defects were more pronounced upon Lhx2 disruption in progenitors, and were recapitulated when this was driven exclusively in basal progenitors. In postmitotic neurons, LHX2 regulates dendritic and spine morphogenesis via the canonical Wnt /{beta} Catenin signalling pathway. Constitutive activation of this pathway in postmitotic neurons mimics the Lhx2 loss-of-function phenotype. In E15.5 progenitors, LHX2 acts in part via bHLH transcription factor NEUROG2 to regulate dendritic morphogenesis. We demonstrate that loss of Lhx2 causes a massive increase in Neurog2 expression, and that Neurog2 knockdown partially rescues the loss of Lhx2 phenotype. Our study uncovers novel LHX2 functions consistent with its temporally dynamic and diverse roles in development. TeaserThe mature architecture of a neuron is shaped by distinct genetic mechanisms that act in its mother cell and after it is born.

neuroscience↗

bioRxiv2023

CRISPRmap: Sequencing-free optical pooled screens mapping multi-omic phenotypes in cells and tissue

Pooled genetic screens are powerful tools to study gene function in a high-throughput manner. Typically, sequencing-based screens require cell lysis, which limits the examination of critical phenotypes such as cell morphology, protein subcellular localization, and cell-cell/tissue interactions. In contrast, emerging optical pooled screening methods enable the investigation of these spatial phenotypes in response to targeted CRISPR perturbations. In this study, we report a multi-omic optical pooled CRISPR screening method, which we have named CRISPRmap. Our method combines a novel in situ CRISPR guide identifying barcode readout approach with concurrent multiplexed immunofluorescence and in situ RNA detection. CRISPRmap barcodes are detected and read out through combinatorial hybridization of DNA oligos, enhancing barcode detection efficiency, while reducing both dependency on third party proprietary sequencing reagents and assay cost. Notably, we conducted a multi-omic base-editing screen in a breast cancer cell line on core DNA damage repair genes involved in the homologous recombination and Fanconi anemia pathways investigating how nucleotide variants in those genes influence DNA damage signaling and cell cycle regulation following treatment with ionizing radiation or DNA damaging agents commonly used for cancer therapy. Approximately a million cells were profiled with our multi-omic approach, providing a comprehensive phenotypic assessment of the functional consequences of the studied variants. CRISPRmap enabled us to pinpoint likely-pathogenic patient-derived mutations that were previously classified as variants of unknown clinical significance. Furthermore, our approach effectively distinguished barcodes of a pooled library in tumor tissue, and we coupled it with cell-type and molecular phenotyping by cyclic immunofluorescence. Multi-omic spatial analysis of how CRISPR-perturbed cells respond to various environmental cues in the tissue context offers the potential to significantly expand our understanding of tissue biology in both health and disease.

genomics↗

bioRxiv2023

Adaptive algorithms for shaping behavior

Dogs and laboratory mice are commonly trained to perform complex tasks by guiding them through a curriculum of simpler tasks ( shaping). What are the principles behind effective shaping strategies? Here, we propose a machine learning framework for shaping animal behavior, where an autonomous teacher agent decides its students task based on the students transcript of successes and failures on previously assigned tasks. Using autonomous teachers that plan a curriculum in a common sequence learning task, we show that near-optimal shaping algorithms adaptively alternate between simpler and harder tasks to carefully balance reinforcement and extinction. Based on this intuition, we derive an adaptive shaping heuristic with minimal parameters, which we show is near-optimal on the sequence learning task and robustly trains deep reinforcement learning agents on navigation tasks that involve sparse, delayed rewards. Extensions to continuous curricula are explored. Our work provides a starting point towards a general computational framework for shaping animal behavior.

animal behavior and cognition↗

bioRxiv2023

Simulated digestion, uptake and colonic fermentation of Gorse (Ulex europeaus) suggests safe use as a source of protein concentrates and potential bioactives.

BackgroundInvasive plants such as Gorse (Ulex europeaus) may serve as a potentially sustainable source of edible proteins and bioactives through the production of leaf protein concentrates (GLPC). The digestion, uptake and safety of phytochemicals from GLPC and the protein depleted but bioactive rich fraction (PDF) from Gorse was studied using an in vitro simulated digestion model. ResultsBoth the Gorse fractions and their digesta maintained the viability of cultured (Caco-2) intestinal cells above the 80% threshold, suggesting a lack of overt toxicity. In the digestion model, most of the plant metabolites in the digesta were largely confined to the apical fraction of the Caco-2 monolayer (representing the lumen) and were subsequently expected to be delivered to the colon. Food matrix had a significant but marginal effect on the permeability of metabolites across the Caco-2 monolayer. Lastly, in vitro intestinal microbial action appeared to produce beneficial compounds such as enterolactones, and equol. ConclusionThe Gorse fractions lack general overt toxicity to Caco-2 cells. GLPC and PDF provide metabolic substrates for the colonic microbes to produce secondary compounds that are associated with positive health outcomes.

biochemistry↗

bioRxiv2023

Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum functions

GRP170, a product of the Hyou1 gene, is required for mouse embryonic development, and its ablation in kidney nephrons leads to renal failure. Unlike most chaperones, GRP170 is the lone member of its chaperone family in the ER lumen. However, the cellular requirement for GRP170, which both binds non-native proteins and acts as nucleotide exchange factor for BiP, is poorly understood. Here, we report on the isolation of embryonic fibroblasts from mice in which LoxP sites were engineered in the Hyou1 loci (Hyou1LoxP/LoxP). A doxycycline-regulated Cre recombinase was also stably introduced into these cells. Induction of Cre resulted in excision of Hyou1 and depletion of Grp170 protein, culminating in apoptotic cell death. As Grp170 levels fell we observed increased steady-state binding of BiP to a client, slowed degradation of a misfolded BiP substrate, and BiP accumulation in NP40-insoluble fractions. Consistent with disrupted BiP functions, we observed reactivation of BiP storage pools and induction of the unfolded protein response (UPR) in futile attempts to provide compensatory increases in ER chaperones and folding enzymes. Together, these results provide insights into the cellular consequences of controlled Grp170 loss and insights into mutations in the Hyou1 locus and human disease.

cell biology↗

bioRxiv2023

Gorse (Ulex europeaus) wastes with 5,6-dimethyl benzimidazole supplementation can support growth of vitamin B12 producing commensal gut microbes

Many commensal gut microbes are recognized for their potential to synthesize vitamin B12, offering a promising avenue to address deficiencies through probiotic supplementation. While bioinformatics tools aid in predicting B12 biosynthetic potential, empirical validation remains crucial to confirm production, identify cobalamin vitamers, and establish biosynthetic yields. This study investigates vitamin B12 production in three human colonic bacterial species: Anaerobu-tyricum hallii DSM 3353, Roseburia faecis DSM 16840, and Anaerostipes caccae DSM 14662, along with Propionibacterium freudenreichii DSM 4902 as a positive control. These strains were selected for their potential use as probiotics, based on speculated B12 production from prior bioinformatic analyses. Cultures were grown in M2GSC, chemically defined media (CDM), and Gorse extract medium (GEM). The composition of GEM was similar to CDM, expect that the carbon and nitrogen source was replaced with protein-depleted liquid wastes obtained after subjecting Gorse to a leaf protein extraction process. B12 yields were quantified using liquid chromatography with tandem mass spectrophotometry. The results suggest that the three butyrate-producing strains could indeed produce B12, although the yields were notably low, and with no B12 being detected in the extracellular media. Next, GEM outperformed the conventional M2GSC growth medium in enhancing B12 production. The positive control, P. freudenreichii DSM 4902 produced B12 at concentrations ranging from 7 ng{middle dot}mL-1 to 12 ng{middle dot}mL-1. Univariate-scaled Principal Component Analysis of data from previous publications investigating B12 production in P. freudenreichii revealed that B12 yields diminished when the carbon source concentration was[≤] 30 g{middle dot}L-1. In conclusion, the protein-depleted wastes from the leaf protein extraction process from Gorse can be valorised as a viable substrate for culturing B12-producing colonic gut microbes. Furthermore, this is the first report attesting to the ability of A. hallii, R. faecis, and A. caccae to produce B12. However, these microbes seem unsuitable for industrial applications owing to low B12 yields.

microbiology↗

bioRxiv2022

Technical Note: STRATIS: A Cloud-enabled Software Toolbox for Radiotherapy and Imaging Analysis

PurposeRecent advances in computational resources, including software libraries and hardware, have enabled the use of high-dimensional, multi-modal datasets to build Artificial Intelligence (AI) models and workflows for radiation therapy and image analysis. The purpose of Software Toolbox for RAdioTherapy and Imaging analysiS (STRATIS) is to provide cloud-enabled, easy-to-share software workflows to train and deploy AI models for transparency and multi-institutional collaboration. MethodSTRATIS leverages open source medical image informatics software for application-specific analysis. Jupyter notebooks for AI modeling workflows are provided with Python language as the base kernel. In addition to Python, workflows use software written in other languages, such as MATLAB, GNU-Octave, R, and C++, with the help of bridge libraries. The workflows can be run on a cloud platform, local workstation, or an institutional HPC cluster. Computational environments are provided in the form of publicly available docker images -and build scripts for local Anaconda environments. Utilities provided with STRATIS simplify bookkeeping of associations between imaging objects and allow chaining data processing operations defined via a setting file for AI models. ResultsWorkflows available on STRATIS can be broadly categorized into image segmentation, deformable image registration, and outcomes modeling for radiotherapy toxicity and tumor control using radiomics and dosimetry features. The STRATIS-forge GitHub organization https://www.github.com/stratis-forge hosts build-scripts for Docker and Anaconda as well as Jupyter notebooks for analysis workflows. The software for building environments and workflow notebooks has open source-GNU-GPL copyright, and AI models retain the copyright chosen by their original developers. ConclusionSTRATIS enables researchers to deploy and share AI modeling workflows for radiotherapy and image analysis. STRATIS is publicly available on Terra.bios FireCloud platform with a pre-deployed computational environment and on GitHub organization for users pursuing local deployment.

bioinformatics↗

bioRxiv2022

The cut site specificity of the influenza A virus endoribonuclease PA-X allows it to discriminate between host and viral mRNAs

Widespread shutoff of host gene expression through RNA degradation is an advantageous way for many viruses to block antiviral responses. However, viruses still need to maintain expression of their own genes and host genes necessary for replication. The influenza A virus host shutoff endoribonuclease PA-X solves this problem by sparing viral mRNAs and some host RNAs. To understand how PA-X distinguishes between RNAs, we characterized PA-X cut sites transcriptome-wide. This analysis shows that PA-Xs from multiple influenza strains cleave RNAs at GCUG tetramers in hairpin loops. Importantly, GCUG tetramers are enriched in the human but not the influenza transcriptome. Moreover, optimal PA-X cut sites inserted in the influenza A virus genome are quickly selected against during viral replication. This finding suggests that PA-X evolved these cleavage characteristics to target host but not viral mRNAs, in a manner reminiscent of cellular self vs. non-self discrimination.

microbiology↗

bioRxiv2022

A combined experimental-computational approach uncovers a role for the Golgi matrix protein Giantin in breast cancer progression

Few studies so far have investigated the impact of different cell migration traits on tumor progression. To address this, we developed a mathematical model wherein cells migrate in two-dimensional space, divide, die or intravasate into the vasculature. Exploring a wide range of speed and persistence combinations, we find that tumor growth positively correlates with increasing speed and higher persistence. As a biologically relevant example, we focused on Golgi fragmentation induced by depletion of Giantin, a Golgi matrix protein, the downregulation of which correlates with poor patient survival. Applying the migration and invasion traits of Giantin depleted cells to our mathematical model, we predict that loss of Giantin increases the number of intravasating cells. This prediction was validated, by showing that circulating tumor cells express significantly less Giantin than primary tumor cells. Altogether, our computational model identifies cell migration traits that regulate tumor progression and uncovers a role of Giantin in breast cancer progression.

cancer biology↗

bioRxiv2021

A microRNA cluster downstream of the selector gene Fezf2 coordinates fate specification with dendritic branching in cortical neurons

In the cerebral cortex, cortical projection neurons comprise classes of neurons project to distant regions of the central nervous system. These neurons develop from the same progenitor pool, but they acquire strikingly different inputs and outputs to underpin strikingly different functions. The question of how corticospinal projection neurons - involved in motor function and implicated in paralysis - and callosal projection neurons - involved in cognitive function and implicated in autism - develop represents a fundamental and clinically important question in neurodevelopment. A network of transcription factors, including the selector gene Fezf2, is central to specifying cortical projection neuron fates. Gene regulation up- and down-stream of these transcription factors, however, is not well understood, particularly as it relates to the development of the major inputs to cortical projection neurons. Here we show that the miR-193b~365 microRNA cluster downstream of Fezf2 cooperatively represses the signaling molecule Mapk8, and impacts dendritic branching of cortical projection neurons.

developmental biology↗

bioRxiv2021

The endoplasmic reticulum membrane protein complex localizes to the mitochondrial - endoplasmic reticulum interface and its subunits modulate phospholipid biosynthesis in Trypanosoma brucei

The endoplasmic reticulum membrane complex (EMC) is a versatile complex that plays a key role in membrane protein biogenesis in the ER. Deletion of the complex has wide-ranging consequences including ER stress, disturbance in lipid transport and organelle tethering, among others. Here we report the function and organization of the evolutionarily conserved EMC (TbEMC) in the highly diverged eukaryote, Trypanosoma brucei. Using (co-) immunoprecipitation experiments in combination with mass spectrometry and whole cell proteomic analyses of parasites after depletion of select TbEMC subunits, we demonstrate that the TbEMC is composed of 9 subunits that are present in a high molecular mass complex localizing to the mitochondrial-endoplasmic reticulum interface. Knocking out or knocking down of single TbEMC subunits led to growth defects of T. brucei procyclic forms in culture. Interestingly, we found that depletion of individual TbEMC subunits lead to disruption of de novo synthesis of phosphatidylcholine (PC) or phosphatidylethanolamine (PE), the two most abundant phospholipid classes in T. brucei. Downregulation of TbEMC1 or TbEMC3 inhibited formation of PC while depletion of TbEMC8 inhibited PE synthesis, pointing to a role of the TbEMC in phospholipid synthesis. In addition, we found that in TbEMC7 knock-out parasites, TbEMC3 is released from the complex, implying that TbEMC7 is essential for the formation or the maintenance of the TbEMC.

biochemistry↗

bioRxiv2021

Transcriptomic Changes During Stage Progression of Mycosis Fungoides

BackgroundMycosis fungoides (MF) is the most common cutaneous T cell lymphoma, which in the early patch/plaque stages runs an indolent course. However, ~25% of MF patients develop skin tumors, a hallmark of progression to the advanced stage and associated with high mortality. The mechanisms involved in stage progression are poorly elucidated. MethodsWe performed whole-transcriptome and whole-exome sequencing of malignant MF cells from skin biopsies obtained by laser-capture microdissection. We compared three types of MF lesions: early-stage plaques (ESP, n=12), and plaques and tumors from patients in late-stage disease (late-stage plaques, LSP, n=10, and tumors, TMR, n=15). Gene Ontology (GO) and KEGG analysis were used to determine pathway changes specific for different lesions which we linked to the recurrent somatic mutations overrepresented in MF tumors. ResultsThe key upregulated pathways during stage progression were those related to cell proliferation and survival (MEK/ERK, Akt-mTOR), Th2/Th9 signaling (IL4, STAT3, STAT5, STAT6), meiomitosis (CT45A1, CT45A3, STAG3, GTSF1, and REC8) and DNA repair (PARP1, MYCN, OGG1). Principal coordinate clustering of the transcriptome revealed extensive gene expression differences between early (ESP) and advanced-stage lesions (LSP and TMR). LSP and TMR showed remarkable similarities at the level of the transcriptome, which we interpreted as evidence of cell percolation between lesions via hematogenous self-seeding. ConclusionStage progression in MF is associated with Th2/Th9 polarization of malignant cells, activation of proliferation, survival, as well as increased genomic instability. Global transcriptomic changes in multiple lesions are probably caused by hematogenous cell percolation between discrete skin lesions.

bioinformatics↗

bioRxiv2021

Portable framework to deploy deep learning segmentation models for medical images

PurposeThis work presents a framework for deployment of deep learning image segmentation models for medical images across different operating systems and programming languages. MethodsComputational Environment for Radiological Research (CERR) platform was extended for deploying deep learning-based segmentation models to leverage CERRs existing functionality for radiological data import, transformation, management, and visualization. The framework is compatible with MATLAB as well as GNU Octave and Python for license-free use. Pre and post processing configurations including parameters for pre-processing images, population of channels, and post-processing segmentations was standardized using JSON format. CPU and GPU implementations of pre-trained deep learning segmentation models were packaged using Singularity containers for use in Linux and Conda environment archives for Windows, macOS and Linux operating systems. The framework accepts images in various formats including DICOM and CERRs planC and outputs segmentation in various formats including DICOM RTSTRUCT and planC objects. The ability to access the results readily in planC format enables visualization as well as radiomics and dosimetric analysis. The framework can be readily deployed in clinical software such as MIM via their extensions. ResultsThe open-source, GPL copyrighted framework developed in this work has been successfully used to deploy Deep Learning based segmentation models for five in-house developed and published models. These models span various treatment sites (H&N, Lung and Prostate) and modalities (CT, MR). Documentation for their usage and demo workflow is provided at https://github.com/cerr/CERR/wiki/Auto-Segmentation-models. The framework has also been used in clinical workflow for segmenting images for treatment planning and for segmenting publicly available large datasets for outcomes studies. ConclusionsThis work presented a comprehensive, open-source framework for deploying deep learning-based medical image segmentation models. The framework was used to translate the developed models to clinic as well as reproducible and consistent image segmentation across institutions, facilitating multi-institutional outcomes modeling studies.

bioinformatics↗

bioRxiv2020

An evolutionarily conserved Lhx2-Ldb1 interaction regulates the acquisition of hippocampal cell fate and regional identity

Protein cofactor Ldb1 regulates cell fate specification by interacting with LIM-homeodomain (LIM-HD) proteins in a tetrameric complex consisting of an LDB:LDB dimer that bridges two LIM-HD molecules, a mechanism first demonstrated in the Drosophila wing disc. Here, we demonstrate conservation of this interaction in the regulation of mammalian hippocampal development, which is profoundly defective upon loss of either Lhx2 or Ldb1. Electroporation of a chimeric construct that encodes the Lhx2-HD and Ldb1-DD (dimerization domain) in a single transcript cell-autonomously rescues a comprehensive range of hippocampal deficits in the mouse Ldb1 mutant, including the acquisition of field-specific molecular identity and the regulation of the neuron-glia cell fate switch. This demonstrates that the LHX:LDB complex is an evolutionarily conserved molecular regulatory device that controls complex aspects of regional cell identity in the developing brain. Summary statementSimilar to an Apterous-Chip mechanism that patterns the Drosophila wing blade, interaction between mammalian orthologs Lhx2 and Ldb1 regulates multiple aspects of hippocampal development in the mouse.

neuroscience↗