Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging.

Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes. We simultaneously profiled 53,417 hematopoietic cells and predicted their interactions with non-hematopoietic subsets. We employed co-detection by indexing (CODEX) to spatially profile over 1.2 million cells. We integrated scRNA-seq and CODEX data to link predicted cellular signaling with spatial proximity. Our analysis revealed a hyperoxygenated arterio-endosteal neighborhood for early myelopoiesis, and an adipocytic localization for early hematopoietic stem and progenitor cells (HSPCs). We used our CODEX atlas to annotate new images and uncovered mesenchymal stromal cell (MSC) expansion and spatial neighborhoods co-enriched for leukemic blasts and MSCs in acute myeloid leukemia (AML) patient samples. This spatially resolved, multiomic atlas of human bone marrow provides a reference for investigation of cellular interactions that drive hematopoiesis.

Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic Imaging.

The bone marrow is the organ responsible for blood production. Diverse non-hematopoietic cells contribute essentially to hematopoiesis. However, these cells and their spatial organization remain largely uncharacterized as they have been technically challenging to study in humans. Here, we used fresh femoral head samples and performed single-cell RNA sequencing (scRNA-Seq) to profile 29,325 enriched non-hematopoietic bone marrow cells and discover nine transcriptionally distinct subtypes. We next employed CO-detection by inDEXing (CODEX) multiplexed imaging of 18 individuals, including both healthy and acute myeloid leukemia (AML) samples, to spatially profile over one million single cells with a novel 53-antibody panel. We discovered a relatively hyperoxygenated arterio-endosteal niche for early myelopoiesis, and an adipocytic, but not endosteal or perivascular, niche for early hematopoietic stem and progenitor cells. We used our atlas to predict cell type labels in new bone marrow images and used these predictions to uncover mesenchymal stromal cell (MSC) expansion and leukemic blast/MSC-enriched spatial neighborhoods in AML patient samples. Our work represents the first comprehensive, spatially-resolved multiomic atlas of human bone marrow and will serve as a reference for future investigation of cellular interactions that drive hematopoiesis.

BAWGNet: Boundary aware wavelet guided network for the nuclei segmentation in histopathology images.

Precise cell nucleus segmentation is very critical in many biologically related analyses and disease diagnoses. However, the variability in nuclei structure, color, and modalities of histopathology images make the automatic computer-aided nuclei segmentation task very difficult. Traditional encoder-decoder based deep learning schemes mainly utilize the spatial domain information that may limit the performance of recognizing small nuclei regions in subsequent downsampling operations. In this paper, a boundary aware wavelet guided network (BAWGNet) is proposed by incorporating a boundary aware unit along with an attention mechanism based on a wavelet domain guidance in each stage of the encoder-decoder output. Here the high-frequency 2 Dimensional discrete wavelet transform (2D-DWT) coefficients are utilized in the attention mechanism to guide the spatial information obtained from the encoder-decoder output stages to leverage the nuclei segmentation task. On the other hand, the boundary aware unit (BAU) captures the nuclei's boundary information, ensuring accurate prediction of the nuclei pixels in the edge region. Furthermore, the preprocessing steps used in our methodology confirm the data's uniformity by converting it to similar color statistics. Extensive experimentations conducted on three benchmark histopathology datasets (DSB, MoNuSeg and TNBC) exhibit the outstanding segmentation performance of the proposed method (with dice scores 90.82%, 85.74%, and 78.57%, respectively). Implementation of the proposed architecture is available at https://github.com/tamjidimtiaz/BAWGNet.

CapsCovNet: A Modified Capsule Network to Diagnose COVID-19 From Multimodal Medical Imaging.

Since the end of 2019, novel coronavirus disease (COVID-19) has brought about a plethora of unforeseen changes to the world as we know it. Despite our ceaseless fight against it, COVID-19 has claimed millions of lives, and the death toll exacerbated due to its extremely contagious and fast-spreading nature. To control the spread of this highly contagious disease, a rapid and accurate diagnosis can play a very crucial part. Motivated by this context, a parallelly concatenated convolutional block-based capsule network is proposed in this article as an efficient tool to diagnose the COVID-19 patients from multimodal medical images. Concatenation of deep convolutional blocks of different filter sizes allows us to integrate discriminative spatial features by simultaneously changing the receptive field and enhances the scalability of the model. Moreover, concatenation of capsule layers strengthens the model to learn more complex representation by presenting the information in a fine to coarser manner. The proposed model is evaluated on three benchmark datasets, in which two of them are chest radiograph datasets and the rest is an ultrasound imaging dataset. The architecture that we have proposed through extensive analysis and reasoning achieved outstanding performance in COVID-19 detection task, which signifies the potentiality of the proposed model.