bioRxiv Science⌕ Search

Biology subjects

Rao, A. K.

Publications and source records attributed to Rao, A. K..

4 recordsLinked to original sources

FeatureForest: the power of foundation models, theusability of random forests

Once the work at the microscope is done, biological discoveries rely heavily on proper downstream analysis. This often amounts to first segmenting the biological objects of interest in the image before performing a quantitative analysis. Deep-learning (DL) is nowadays ubiquitous in such segmentation tasks. However, DL can be cumbersome to apply, as it often requires large amount of manual labeling to produce ground-truth data, and expert knowledge to train the models from scratch. Nonetheless, the performance of large foundation models, although trained on natural images, are improving on scientific images with every new model released. They, however, require either manual prompting or tedious post-processing to selectively segment the biological objects of interest. Classical machine learning algorithms, such as random forest classifiers, on the other hand, are well-established, easy to train, and often yield results of sufficient quality for downstream processing tasks, hence their continued popularity. Unfortunately, they are limited to objects with distinct, well-defined textures compared to their environment. This generally limits their usefulness to structures easy to recognize. Here, we present FeatureForest, an open-source tool that leverages the feature embeddings of large foundation models to train a random forest classifier, thereby providing users with a rapid way of semantically segmenting complex images using only a few labeling strokes. We demonstrate the improvement in performance over a variety of datasets, including large and complex volumetric electron microscopy stacks. Our implementation is available in napari, currently integrates four foundation models, and can easily be extended to any new model once they become available.

bioinformatics↗

Hijacking and Integration of Algal Plastids andMitochondria in a Polar Planktonic Host

In oceanic plankton, various host organisms are capable of engulfing and temporarily integrating microalgae (photosymbiosis) or just their photosynthetic plastids (kleptoplastidy) as a solar-powered energy source. These cellular interactions can be considered to be representative of evolutionary steps in plastid acquisition in eukaryotes, but the underlying cellular mechanisms and dynamics are not fully understood. Here, we studied a kleptoplastidic dinoflagellate (RSD: Ross Sea Dinoflagellate), which is known to steal plastids of the microalga Phaeocystis antarctica. We tracked the morphology and activity of stolen plastids over several months by combining multimodal subcellular imaging and photophysiology. Upon integration inside a host vacuole, the volume of plastids and pyrenoids significantly increased and photosynthetic activity was boosted along with carbon fixation and transfer to the host. This may be supported by the retention of a 50-fold larger algal nucleus for [~]1 week. Once the algal nucleus was lost, there was a decrease in plastid volume and photosynthesis, but plastids were still beneficial for the host after > 2 months. Unlike other kleptoplastidic interactions, we showed that the algal mitochondrion was also stolen and retained for several months, transforming into an extensive network in close proximity with plastids. This highlights a new strategy in plankton along the continuum of plastid symbioses where both the energy-producing plastid and mitochondrion of a microalga are hijacked for several months by a host. This symbiosis that we found to be widely-distributed in polar regions suggests that plastid-mitochondrion interaction may have played a role in the evolution of plastid acquisition.

ecology↗

RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical Cardiovascular Events

BackgroundHematopoietic transcription factor RUNX1 is expressed from proximal P2 and distal P1 promoter to yield isoforms RUNX1 B and C, respectively. The roles of these isoforms in RUNX1 autoregulation and downstream-gene regulation in megakaryocytes and platelets are unknown. ObjectivesTo understand the regulation of RUNX1 and its target genes by RUNX1 isoforms. MethodsWe performed studies on RUNX1 isoforms in megakaryocytic HEL cells and HeLa cells (lack endogenous RUNX1), in platelets from 85 healthy volunteers administered aspirin or ticagrelor, and on the association of RUNX1 target genes with acute events in 587 patients with cardiovascular disease (CVD). ResultsIn chromatin immunoprecipitation and luciferase promoter assays, RUNX1 isoforms B and C bound and regulated P1 and P2 promoters. In HeLa cells RUNX1B decreased and RUNX1C increased P1 and P2 activities, respectively. In HEL cells, RUNX1B overexpression decreased RUNX1C and RUNX1A expression; RUNX1C increased RUNX1B and RUNX1A. RUNX1B and RUNX1C regulated target genes (MYL9, F13A1, PCTP, PDE5A and others) differentially in HEL cells. In platelets RUNX1B transcripts (by RNAseq) correlated negatively with RUNX1C and RUNX1A; RUNX1C correlated positively with RUNX1A. RUNX1B correlated positively with F13A1, PCTP, PDE5A, RAB1B, and others, and negatively with MYL9. In our previous studies, RUNX1C transcripts in whole blood were protective against acute events in CVD patients. We found that higher expression of RUNX1 targets F13A1 and RAB31 associated with acute events. ConclusionsRUNX1 isoforms B and C autoregulate RUNX1 and regulate downstream genes in a differential manner and this associates with acute events in CVD. Scientific categoryPlatelets EssentialsO_LIRUNX1 is expressed from 2 promoters (P1 and P2) to yield isoforms RUNX1C and RUNX1B. C_LIO_LIRUNX1B and RUNX1C regulate RUNX1 and target genes differentially in megakaryocytes/platelets. C_LIO_LIIn platelets RUNX1B and RUNX1C expression is inversely related and ticagrelor increases RUNX1C C_LIO_LIRUNX1 target gene (F13A1, RAB31) expression in blood is associated with death or MI in cardiac disease. C_LI

cell biology↗

Multiple lineages of Monkeypox virus detected in the United States, 2021-2022

Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of Monkeypox virus (MPXV) among nine 2021 and 2022 U.S. monkeypox cases. A 2021 case was highly similar to the 2022 MPXV outbreak variant, suggesting a common ancestor. Analysis of mutations among these two lineages revealed an extreme preference for GA-to-AA mutations indicative of APOBEC3 cytosine deaminase activity that was shared among West African MPXV since 2017 but absent from Congo Basin lineages. Poxviruses are not thought to be subject to APOBEC3 editing; however, these findings suggest APOBEC3 activity has been recurrent and dominant in recent West African MPXV evolution.

genomics↗