DeepPocket: Ligand Binding Site Detection and Segmentation using 3D Convolutional Neural Networks.

A structure-based drug design pipeline involves the development of potential drug molecules or ligands that form stable complexes with a given receptor at its binding site. A prerequisite to this is finding druggable and functionally relevant binding sites on the 3D structure of the protein. Although several methods for detecting binding sites have been developed beforehand, a majority of them surprisingly fail in the identification and ranking of binding sites accurately. The rapid adoption and success of deep learning algorithms in various sections of structural biology beckons the usage of such algorithms for accurate binding site detection. As a combination of geometry based software and deep learning, we report a novel framework, DeepPocket that utilizes 3D convolutional neural networks for the rescoring of pockets identified by Fpocket and further segments these identified cavities on the protein surface. Apart from this, we also propose another data set SC6K containing protein structures submitted in the Protein Data Bank (PDB) from January 1st, 2018, until February 28th, 2020, for ligand binding site (LBS) detection. DeepPocket's results on various binding site data sets and SC6K highlight its better performance over current state-of-the-art methods and good generalization ability over novel structures.

Machine Learning for Accurate Force Calculations in Molecular Dynamics Simulations.

The computationally expensive nature of ab initio molecular dynamics simulations severely limits its ability to simulate large system sizes and long time scales, both of which are necessary to imitate experimental conditions. In this work, we explore an approach to make use of the data obtained using the quantum mechanical density functional theory (DFT) on small systems and use deep learning to subsequently simulate large systems by taking liquid argon as a test case. A suitable vector representation was chosen to represent the surrounding environment of each Ar atom, and a Δ-NetFF machine learning model, where the neural network was trained to predict the difference in resultant forces obtained by DFT and classical force fields, was introduced. Molecular dynamics simulations were then performed using forces from the neural network for various system sizes and time scales depending on the properties we calculated. A comparison of properties obtained from the classical force field and the neural network model was presented alongside available experimental data to validate the proposed method.

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

Generating Personalized Summaries of Day Long Egocentric Videos.

The popularity of egocentric cameras and their always-on nature has lead to the abundance of day long first-person videos. The highly redundant nature of these videos and extreme camera-shakes make them difficult to watch from beginning to end. These videos require efficient summarization tools for consumption. However, traditional summarization techniques developed for static surveillance videos or highly curated sports videos and movies are either not suitable or simply do not scale for such hours long videos in the wild. On the other hand, specialized summarization techniques developed for egocentric videos limit their focus to important objects and people. This paper presents a novel unsupervised reinforcement learning framework to summarize egocentric videos both in terms of length and the content. The proposed framework facilitates incorporating various prior preferences such as faces, places, or scene diversity and interactive user choice in terms of including or excluding the particular type of content. This approach can also be adapted to generate summaries of various lengths, making it possible to view even 1-minute summaries of one's entire day. When using the facial saliency-based reward, we show that our approach generates summaries focusing on social interactions, similar to the current state-of-the-art (SOTA). The quantitative comparisons on the benchmark Disney dataset show that our method achieves significant improvement in Relaxed F-Score (RFS) (29.60 compared to 19.21 from SOTA), BLEU score (0.68 compared to 0.67 from SOTA), Average Human Ranking (AHR), and unique events covered. Finally, we show that our technique can be applied to summarize traditional, short, hand-held videos as well, where we improve the SOTA F-score on benchmark SumMe and TVSum datasets from 41.4 to 46.40 and 57.6 to 58.3 respectively. We also provide a Pytorch implementation and a web demo at https://pravin74.github.io/Int-sum/index.html.

AI-Assisted Screening of Oral Potentially Malignant Disorders Using Smartphone-Based Photographic Images.

The prevalence of oral potentially malignant disorders (OPMDs) and oral cancer is surging in low- and middle-income countries. A lack of resources for population screening in remote locations delays the detection of these lesions in the early stages and contributes to higher mortality and a poor quality of life. Digital imaging and artificial intelligence (AI) are promising tools for cancer screening. This study aimed to evaluate the utility of AI-based techniques for detecting OPMDs in the Indian population using photographic images of oral cavities captured using a smartphone. A dataset comprising 1120 suspicious and 1058 non-suspicious oral cavity photographic images taken by trained front-line healthcare workers (FHWs) was used for evaluating the performance of different deep learning models based on convolution (DenseNets) and Transformer (Swin) architectures. The best-performing model was also tested on an additional independent test set comprising 440 photographic images taken by untrained FHWs (set I). DenseNet201 and Swin Transformer (base) models show high classification performance with an F1-score of 0.84 (CI 0.79-0.89) and 0.83 (CI 0.78-0.88) on the internal test set, respectively. However, the performance of models decreases on test set I, which has considerable variation in the image quality, with the best F1-score of 0.73 (CI 0.67-0.78) obtained using DenseNet201. The proposed AI model has the potential to identify suspicious and non-suspicious oral lesions using photographic images. This simplified image-based AI solution can assist in screening, early detection, and prompt referral for OPMDs.

Removing Atmospheric Turbulence via Deep Adversarial Learning.

Restoring images degraded due to atmospheric turbulence is challenging as it consists of several distortions. Several deep learning methods have been proposed to minimize atmospheric distortions that consist of a single-stage deep network. However, we find that a single-stage deep network is insufficient to remove the mixture of distortions caused by atmospheric turbulence. We propose a two-stage deep adversarial network that minimizes atmospheric turbulence to mitigate this. The first stage reduces the geometrical distortion and the second stage minimizes the image blur. We improve our network by adding channel attention and a proposed sub-pixel mechanism, which utilizes the information between the channels and further reduces the atmospheric turbulence at the finer level. Unlike previous methods, our approach neither uses any prior knowledge about atmospheric turbulence conditions at inference time nor requires the fusion of multiple images to get a single restored image. Our final restoration models DT-GAN+ and DTD-GAN+ outperform the general state-of-the-art image-to-image translation models and baseline restoration models. We synthesize turbulent image datasets to train the restoration models. Additionally, we also curate a natural turbulent dataset from YouTube to show the generalisability of the proposed model. We perform extensive experiments on restored images by utilizing them for downstream tasks such as classification, pose estimation, semantic keypoint estimation, and depth estimation. We observe that our restored images outperform turbulent images in downstream tasks by a significant margin demonstrating the restoration model's applicability in real-world problems.

Exploring Histological Similarities Across Cancers From a Deep Learning Perspective.

Histopathology image analysis is widely accepted as a gold standard for cancer diagnosis. The Cancer Genome Atlas (TCGA) contains large repositories of histopathology whole slide images spanning several organs and subtypes. However, not much work has gone into analyzing all the organs and subtypes and their similarities. Our work attempts to bridge this gap by training deep learning models to classify cancer vs. normal patches for 11 subtypes spanning seven organs (9,792 tissue slides) to achieve high classification performance. We used these models to investigate their performances in the test set of other organs (cross-organ inference). We found that every model had a good cross-organ inference accuracy when tested on breast, colorectal, and liver cancers. Further, high accuracy is observed between models trained on the cancer subtypes originating from the same organ (kidney and lung). We also validated these performances by showing the separability of cancer and normal samples in a high-dimensional feature space. We further hypothesized that the high cross-organ inferences are due to shared tumor morphologies among organs. We validated the hypothesis by showing the overlap in the Gradient-weighted Class Activation Mapping (GradCAM) visualizations and similarities in the distributions of nuclei features present within the high-attention regions.

Pan-Renal Cell Carcinoma classification and survival prediction from histopathology images using deep learning.

Histopathological images contain morphological markers of disease progression that have diagnostic and predictive values. In this study, we demonstrate how deep learning framework can be used for an automatic classification of Renal Cell Carcinoma (RCC) subtypes, and for identification of features that predict survival outcome from digital histopathological images. Convolutional neural networks (CNN's) trained on whole-slide images distinguish clear cell and chromophobe RCC from normal tissue with a classification accuracy of 93.39% and 87.34%, respectively. Further, a CNN trained to distinguish clear cell, chromophobe and papillary RCC achieves a classification accuracy of 94.07%. Here, we introduced a novel support vector machine-based method that helped to break the multi-class classification task into multiple binary classification tasks which not only improved the performance of the model but also helped to deal with data imbalance. Finally, we extracted the morphological features from high probability tumor regions identified by the CNN to predict patient survival outcome of most common clear cell RCC. The generated risk index based on both tumor shape and nuclei features are significantly associated with patient survival outcome. These results highlight that deep learning can play a role in both cancer diagnosis and prognosis.

Optimizing Average Precision Using Weakly Supervised Data.

Many tasks in computer vision, such as action classification and object detection, require us to rank a set of samples according to their relevance to a particular visual category. The performance of such tasks is often measured in terms of the average precision (ap). Yet it is common practice to employ the support vector machine ( svm) classifier, which optimizes a surrogate 0-1 loss. The popularity of svmcan be attributed to its empirical performance. Specifically, in fully supervised settings, svm tends to provide similar accuracy to ap-svm, which directly optimizes an ap-based loss. However, we hypothesize that in the significantly more challenging and practically useful setting of weakly supervised learning, it becomes crucial to optimize the right accuracy measure. In order to test this hypothesis, we propose a novel latent ap-svm that minimizes a carefully designed upper bound on the ap-based loss function over weakly supervised samples. Using publicly available datasets, we demonstrate the advantage of our approach over standard loss-based learning frameworks on three challenging problems: action classification, character recognition and object detection.

Pharmacognostical studies of janakia arayalpatra joseph et. Chandrasekharan (periplocaceae).

Janakia arayalpatra (Periplocaceae) known to the local kani tribe as 'Amruthapala' is a rare and endemic wild plant species of southern forested region of Western Ghats. The medicinal value of this plant as a potential drug was reported by the authors earlier (on the basis of the information collected from the Kani tribe). Preliminary ethnopharmacological investigation of the plant showed promising results. In view of the emerging medical importance of this plant, a detailed pharmacognostical investigation of this plant species was carried out. The plant species is now placed under the family periploaceae which was formerly considered to be a sub-division of the family Asclepiadaceae. Pharmacognostical investigation of the root of this plant showed certain characterstic anatomical features like those of the Asclepiadaceae. The aroma and physical characterstics of the roots have close resemblance with plant species like Utleria salicifolia Bedd. and Hemidesmus indicus R. Br.

'AROGYAPPACHA' (TRICHOPUS ZEYLANICUS gaerin), THE 'GINSENG' OF KANI TRIBES OF AGASHYAR HILLS (KERALA) FOR EVER GREEN HEALH AND VITALITY.

'Arogyappacha' (Trichopus zeylanicus) found endemic to Agastyar hills of Kerala is used by the local 'kani' tribe as a health food for getting instant stamina, ever green health and vitality. The tonic effect of this plants is comparable to that of the famous health food/drug 'Ginseng'. A critical survey of the Ayurveda classics, suggests that the 'Arogyappacha' may be the divine 'Varahi'described by sushruta. Chemical and Pharmacological evaluation of the plant have been initiated.

ETHNO-MEDICO-BOT ANICAL STUDIES OF CHERIYA ARAYAN-AND VALIYA ARAYAN- (Aristolochia indica, Linn; Aristolochia tagala, Cham).

This paper presents two important species of plants used by the Kanitribes of Agastyar hills of Trivandrum district of Kerala against snake-poison and insect bite.

'AMRITHAPALA' (Janakia arayalpatra, Joseph & Chandrasekharan), A NEW DRUG FROM THE KANI TRIBE OF KERALA.

Amrithapala (Janakia arayalpatra), a rare and endemic plant species found in the Southern forests of Western Ghat region of kerala, is used by the local 'Kani' tribe as an effective remedy for peptic ulcer, cancer-like afflictions and as a rejuvenating tonic. Search made in Ayurvedic literature indicates that the plant may be the divine drug named variously as MRITHA SANJEEVINI (the drug that can revive unconscious or dead) or SANJEEVINI, THAMPRA RASAYANI in the Oushadha Nighantu (Dictionary of Medicinal Drugs) of Tayyil Kumaran Krishnan (1906).