Low-Cost Histopathological Mitosis Detection for Microscope-acquired Images.

Cancer outcomes are poor in resource-limited countries owing to high costs and insufficient pathologist-population ratio. The advent of digital pathology has assisted in improving cancer outcomes, however, Whole Slide Image scanners are expensive and not affordable in low-income countries. Microscope-acquired images on the other hand are cheap to collect and can be more viable for automation of cancer detection. In this study, we propose LCH-Network, a novel method to identify the cancer mitotic count from microscope-acquired images. We introduced Label Mix, and also synthesized images using GANs to handle data imbalance. Moreover, we applied progressive resolution to handle different image scales for mitotic localization. We achieved F1-Score of 0.71 and outperformed other existing techniques. Our findings enable mitotic count estimation from microscopic images with a low-cost setup. Clinically, our method could help avoid presumptive treatment without a confirmed cancer diagnosis.

An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation.

The mouse Igh locus is organized into a developmentally regulated topologically associated domain (TAD) that is divided into subTADs. Here we identify a series of distal VH enhancers (EVHs) that collaborate to configure the locus. EVHs engage in a network of long-range interactions that interconnect the subTADs and the recombination center at the DHJH gene cluster. Deletion of EVH1 reduces V gene rearrangement in its vicinity and alters discrete chromatin loops and higher order locus conformation. Reduction in the rearrangement of the VH11 gene used in anti-PtC responses is a likely cause of the observed reduced splenic B1 B cell compartment. EVH1 appears to block long-range loop extrusion that in turn contributes to locus contraction and determines the proximity of distant VH genes to the recombination center. EVH1 is a critical architectural and regulatory element that coordinates chromatin conformational states that favor V(D)J rearrangement.

Leveraging digital media data for pharmacovigilance.

The development of novel drugs in response to changing clinical requirements is a complex and costly method with uncertain outcomes. Postmarket pharmacovigilance is essential as drugs often have under-reported side effects. This study intends to use the power of digital media to discover the under-reported side effects of marketed drugs. We have collected tweets for 11 different Drugs (Alprazolam, Adderall, Fluoxetine, Venlafaxine, Adalimumab, Lamotrigine, Quetiapine, Trazodone, Paroxetine, Metronidazole and Miconazole). We have compiled a vast adverse drug reactions (ADRs) lexicon that is used to filter health related data. We constructed machine learning models for automatically annotating the huge amount of publicly available Twitter data. Our results show that on average 43 known ADRs are shared between Twitter and FAERS datasets. Moreover, we were able to recover on average 7 known side effects from Twitter data that are not reported on FAERS. Our results on Twitter dataset show a high concordance with FAERS, Medeffect and Drugs.com. Moreover, we manually validated some of the under-reported side effect predicted by our model using literature search. Common known and under-reported side effects can be found at https://github.com/cbrl-nuces/Leveraging-digital-media-data-for-pharmacovigilance.

Predicting the pathogenicity of protein coding mutations using Natural Language Processing.

DNA-Sequencing of tumor cells has revealed thousands of genetic mutations. However, cancer is caused by only some of them. Identifying mutations that contribute to tumor growth from neutral ones is extremely challenging and is currently carried out manually. This manual annotation is very cumbersome and expensive in terms of time and money. In this study, we introduce a novel method "NLP-SNPPred" to read scientific literature and learn the implicit features that cause certain variations to be pathogenic. Precisely, our method ingests the bio-medical literature and produces its vector representation via exploiting state of the art NLP methods like sent2vec, word2vec and tf-idf. These representations are then fed to machine learning predictors to identify the pathogenic versus neutral variations. Our best model (NLPSNPPred) trained on OncoKB and evaluated on several publicly available benchmark datasets, outperformed state of the art function prediction methods. Our results show that NLP can be used effectively in predicting functional impact of protein coding variations with minimal complementary biological features. Moreover, encoding biological knowledge into the right representations, combined with machine learning methods can help in automating manual efforts. A free to use web-server is available at http://www.nlp-snppred.cbrlab.org.