Abstract

Deep learning assisted disease diagnosis using chest radiol- ogy images to assess severity of various respiratory conditions has gar- nered a lot of attention after the recent COVID-19 pandemic. Under- standing characteristic features associated with the disease in radiology images, along with variations observed from patient-to-patient and with the progression of disease, is important while building such models. In this work, we carried out comparative analysis of various deep architec- tures with the proposed attention-based Convolutional Neural Network (CNN) model with customized bottleneck residual module (Attn-CNN) in classifying chest CT images into three categories, COVID-19, Normal, and Pneumonia. We show that the attention model with fewer parame- ters achieved better classification performance compared to state-of-the- art deep architectures such as EfficientNet-B7, Inceptionv3, ResNet-50 and VGG-16, and customized models proposed in similar studies such as COVIDNet-CT, CTnet-10, COVID-19Net, etc.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma and frequently develops through the accumulation of several genetic variations. With the advancement in high-throughput techniques, in addition to mutations and copy number variations, structural variations have gained importance for their role in genome instability leading to tumorigenesis. In this study, in order to understand the genetics of DLBCL pathogenesis, we carried out a whole-genome mutation profile analysis of eleven human cell lines from germinal-center B-cell-like (GCB-7) and activated B-cell-like (ABC-4) subtypes of DLBCL. Analysis of genetic variations including small sequence variants and large structural variations across the cell lines revealed distinct variation profiles indicating the heterogeneous nature of DLBCL and the need for novel patient stratification methods to design potential intervention strategies. Validation and prognostic significance of the variants was assessed using annotations provided for DLBCL samples in cBioPortal for Cancer Genomics. Combining genetic variations revealed new subgroups between the subtypes and associated enriched pathways, viz., PI3K-AKT signaling, cell cycle, TGF-beta signaling, and WNT signaling. Mutation landscape analysis also revealed drug–variant associations and possible effectiveness of known and novel DLBCL treatments. From the whole-genome-based mutation analysis, our findings suggest putative molecular genetics of DLBCL lymphomagenesis and potential genomics-driven precision treatments. Keywords: diffuse large B-cell lymphoma (DLBCL); copy number variations; sequence variations; structural variations; cell lines; precision medicine

Abstract

Computer tomography (CT) have been routinely used for the diagnosis of lung diseases and recently, during the pandemic, for detecting the infectivity and severity of COVID-19 disease. One of the major concerns in using ma-chine learning (ML) approaches for automatic processing of CT scan images in clinical setting is that these methods are trained on limited and biased sub-sets of publicly available COVID-19 data. This has raised concerns regarding the generalizability of these models on external datasets, not seen by the model during training. To address some of these issues, in this work CT scan images from confirmed COVID-19 data obtained from one of the largest public repositories, COVIDx CT 2A were used for training and internal vali-dation of machine learning models. For the external validation we generated Indian-COVID-19 CT dataset, an open-source repository containing 3D CT volumes and 12096 chest CT images from 288 COVID-19 patients from In-dia. Comparative performance evaluation of four state-of-the-art machine learning models, viz., a lightweight convolutional neural network (CNN), and three other CNN based deep learning (DL) models such as VGG-16, ResNet-50 and Inception-v3 in classifying CT images into three classes, viz., normal, non-covid pneumonia, and COVID-19 is carried out on these two datasets. Our analysis showed that the performance of all the models is comparable on the hold-out COVIDx CT 2A test set with 90% - 99% accuracies (96% for CNN), while on the external Indian-COVID-19 CT dataset a drop in the performance is observed for all the models (8% - 19%). The traditional ma-chine

Abstract

In this study we carried out a comprehensive analysis of SARS-CoV2 mutations and their spread in India over the past two years of the pandemic (27th Jan’ 2020 – 8th Mar’ 2022). The analysis covers four important timelines, viz., the early phase, followed by the first, second and third waves of the pandemic in the country. Phylogenetic analysis of the isolates indicated multiple independent entries of coronavirus in the country, while principal component analysis identified few state-specific clusters. Genetic analysis of isolates during the first year revealed that though lockdown helped in controlling the spread of the virus, region-specific set of shared mutations were developed during the early phase due to local community transmissions. We thus report the evolution of state-specific subclades, namely, I/GJ-20A (Gujarat), I/MH-2 (Maharashtra), I/Tel-A-20B, I/Tel-B-20B (Telangana), and I/AP-20A (Andhra Pradesh) that explain the demographic variation in the impact of COVID-19 across states. In the second year of the pandemic, India faced an aggressive second wave while the third wave was quite mild in terms of severity. Here we also discuss the prevalence and impact of different lineages and Variants of Concerns/Interests, viz., Delta, Kappa, Omicron, etc. observed during this period. From the genetic analysis of mutation spectra of Indian isolates, the insights gained in its transmission, geographic distribution, containment, and impact are discussed.

Abstract

Deep learning (DL) analysis of Chest X-ray (CXR) and Computed tomography (CT) images has garnered a lot of attention in recent times due to the COVID-19 pandemic. Convolutional Neural Networks (CNNs) are well suited for the image analysis tasks when trained on humongous amounts of data. Applications developed for medical image analysis require high sensitivity and precision compared to any other fields. Most of the tools proposed for detection of COVID-19 claims to have high sensitivity and recalls but have failed to generalize and perform when tested on unseen datasets. This encouraged us to develop a CNN model, analyze and understand the performance of it by visualizing the predictions of the model using class activation maps generated using (Gradient-weighted Class Activation Mapping) Grad-CAM technique. This study provides a detailed discussion of the success and failure of the proposed model at an image level. Performance of the model is compared with state-of-the-art DL models and shown to be comparable. The data and code used are available at https://github.com/aleesuss/c19

Abstract

Recent focus on transcriptomic studies in food crops like rice, wheat and maize provide new opportunities to address issues related to agriculture and climate change. Re-analysis of such data available in public domain supplemented with annotations across molecular hierarchy can be of immense help to the plant research community, particularly co-expression networks representing transcriptionally coordinated genes that are often part of the same biological process. With this objective, we have developed NetREx, a Network-based Rice Expression Analysis Server, that hosts ranked co-expression networks of Oryza sativa using publicly available messenger RNA sequencing data across uniform experimental conditions. It provides a range of interactable data viewers and modules for analysing user-queried genes across different stress conditions (drought, flood, cold and osmosis) and hormonal treatments (abscisic and jasmonic acid) and tissues (root and shoot). Subnetworks of user-defined genes can be queried in pre-constructed tissue-specific networks, allowing users to view the fold change, module memberships, gene annotations and analysis of their neighbourhood genes and associated pathways. The web server also allows querying of orthologous genes from Arabidopsis, wheat, maize, barley and sorghum. Here, we demonstrate that NetREx can be used to identify novel candidate genes and tissue-specific interactions under stress conditions and can aid in the analysis and understanding of complex phenotypes linked to stress response in rice.

Abstract

Ankyrin is one of the most abundant protein repeat families found across all forms of life. It is found in a variety of multi-domain and single domain proteins in humans with diverse number of repeating units. They are observed to occur in several functionally diverse proteins, such as transcriptional initiators, cell cycle regulators, cytoskeletal organizers, ion transporters, signal transducers, developmental regulators, and toxins, and, consequently, defects in ankyrin repeat proteins have been associated with a number of human diseases. In this study, we have classified the human ankyrin proteins into clusters based on the sequence similarity in their ankyrin repeat domains. We analyzed the amino acid compositional bias and consensus ankyrin motif sequence of the clusters to understand the diversity of the human ankyrin proteins. We carried out network-based structural analysis of human ankyrin proteins across different clusters and showed the association of conserved residues with topologically important residues identified by network centrality measures. The analysis of conserved and structurally important residues helps in understanding their role in structural stability and function of these proteins. In this paper, we also discuss the significance of these conserved residues in disease association across the human ankyrin protein clusters.

Abstract

In this study we carried out the early distribution of clades and subclades state-wise based on shared mutations in Indian SARS-CoV-2 isolates collected (27th Jan – 27th May 2020). Phylogenetic analysis of these isolates indicates multiple independent sources of introduction of the virus in the country, while principal component analysis revealed some state-specific clusters. It is observed that clade 20A defining mutations C241T (ORF1ab: 5’ UTR), C3037T (ORF1ab: F924F), C14408T (ORF1ab: P4715L), and A23403G (S: D614G) are predominant in Indian isolates during this period. Higher number of coronavirus cases were observed in certain states, viz., Delhi, Tamil Nadu, and Telangana. Genetic analysis of isolates from these states revealed a cluster with shared mutations, C6312A (ORF1ab: T2016K), C13730T (ORF1ab: A4489V), C23929T, and C28311T (N: P13L). Analysis of region-specific shared mutations carried out to understand the large number of deaths in Gujarat and Maharashtra identified shared mutations defining subclade, I/GJ-20A (C18877T, C22444T, G25563T (ORF3a: H57Q), C26735T, C28854T (N: S194L), C2836T) in Gujarat and two sets of co-occurring mutations C313T, C5700A (ORF1ab: A1812D) and A29827T, G29830T in Maharashtra. From the genetic analysis of mutation spectra of Indian isolates, the insights gained in its transmission, geographic distribution, containment, and impact are discussed.

Abstract

Abstract Recent interest in repeat proteins has arisen due to stable structural folds, high evolutionary conservation and repertoire of functions provided by these proteins. However, repeat proteins are poorly characterized because of high sequence variation between repeating units and structure-based identification and classification of repeats is desirable. Using a robust network-based pipeline, manual curation and Kajava's structure-based classification schema, we have developed a database of tandem structural repeats, Database of Structural Repeats in Proteins (DbStRiPs). A unique feature of this database is that available knowledge on sequence repeat families is incorporated by mapping Pfam classification scheme onto structural classification. Integration of sequence and structure-based classifications help in identifying different functional groups within the same structural subclass, leading to refinement in the annotation of repeat proteins. Analysis of complete Protein Data Bank revealed 16,472 repeat annotations in 15,141 protein chains, one previously uncharacterized novel protein repeat family (PRF), named left-handed beta helix, and 33 protein repeat clusters (PRCs). Based on their unique structural motif,
79% of these repeat proteins are classified in one of the 14 PRFs or 33 PRCs, and the remaining are grouped as unclassified repeat proteins. Each repeat protein is provided with a detailed annotation in DbStRiPs that includes start and end boundaries of repeating units, copy number, secondary and tertiary structure view, repeat class/subclass, disease association, MSA of repeating units and cross-references to various protein pattern databases, human protein atlas and interaction resources. DbStRiPs provides easy search and download options to high-quality annotations of structural repeat proteins (URL: http://bioinf.iiit.ac.in/dbstrips/). KEYWORDS protein repeat database, proteins repeats, structural repeat proteins, tandem repeat

Abstract

Rice blast disease is a major threat to rice production worldwide; the causative pathogenic fungus Magnaporthe oryzae induces rice (Oryza sativa) plants to undergo molecular changes that help them to circumvent this fungal attack. Transcriptome studies have demonstrated that many genes are involved in the defense response of rice to M. oryzae, but most of these studies focused on the screening of differentially expressed genes and the studies did not investigate the interactions among genes. We examined the interaction of rice and M. oryzae in a network context. Two near-isogenic lines were profiled at different time-points. Using transcriptome data obtained from an RNASeq analysis, a network based on the relationships among genes was developed through weighted gene co-expression network analysis. The analysis of degree centrality identified numerous hub genes and potential key regulators that control the rice response, providing new insights into the molecular network underlying the resistance of rice to M. oryzae infection. Additionally, a protein-protein interaction network was derived to identify complexes that might physically interact. For example, complexes of OsbHLH148/OsJAZ, OsMYB4 and some components of the phenylpropanoid pathway, as well as MYB/bHLH