Background: Unsupervised compression algorithms applied to gene expression data extract latent or hidden signals representing technical and biological sources of variation. However, these algorithms require a user to select a biologically appropriate latent space dimensionality. In practice, most researchers fit a single algorithm and latent dimensionality. We sought to determine the extent by which selecting only one fit limits the biological features captured in the latent representations and, consequently, limits what can be discovered with subsequent analyses. Results: We compress gene expression data from three large datasets consisting of adult normal tissue, adult cancer tissue, and pediatric cancer tissue. We train many different models across a large range of latent space dimensionalities and observe various performance differences. We identify more curated pathway gene sets significantly associated with individual dimensions in denoising autoencoder and variational autoencoder models trained using an intermediate number of latent dimensionalities. Combining compressed features across algorithms and dimensionalities captures the most pathway-associated representations. When trained with different latent dimensionalities, models learn strongly associated and generalizable biological representations including sex, neuroblastoma MYCN amplification, and cell types. Stronger signals, such as tumor type, are best captured in models trained at lower dimensionalities, while more subtle signals such as pathway activity are best identified in models trained with more latent dimensionalities. Conclusions: There is no single best latent dimensionality or compression algorithm for analyzing gene expression data. Instead, using features derived from different compression models across multiple latent space dimensionalities enhances biological representations.

Open, collaborative research is a powerful paradigm that can immensely strengthen the scientific process by integrating broad and diverse expertise. However, traditional research and multi-author writing processes break down at scale. We present new software named Manubot, available at https://manubot.org , to address the challenges of open scholarly writing. Manubot adopts the contribution workflow used by many large-scale open source software projects to enable collaborative authoring of scholarly manuscripts. With Manubot, manuscripts are written in Markdown and stored in a Git repository to precisely track changes over time. By hosting manuscript repositories publicly, such as on GitHub, multiple authors can simultaneously propose and review changes. A cloud service automatically evaluates proposed changes to catch errors. Publication with Manubot is continuous: When a manuscript’s source changes, the rendered outputs are rebuilt and republished to a web page. Manubot automates bibliographic tasks by implementing citation by identifier, where users cite persistent identifiers (e.g. DOIs, PubMed IDs, ISBNs, URLs), whose metadata is then retrieved and converted to a user-specified style. Manubot modernizes publishing to align with the ideals of open science by making it transparent, reproducible, immediate, versioned, collaborative, and free of charge.

BackgroundUnsupervised compression algorithms applied to gene expression data extract latent, or hidden, signals representing technical and biological sources of variation. However, these algorithms require a user to select a biologically-appropriate latent dimensionality. In practice, most researchers select a single algorithm and latent dimensionality. We sought to determine the extent by which using multiple dimensionalities across ensemble compression models improves biological representations.ResultsWe compressed gene expression data from three large datasets consisting of adult normal tissue, adult cancer tissue, and pediatric cancer tissue. We compressed these data into many latent dimensionalities ranging from 2 to 200. We observed various tradeoffs across latent dimensionalities and compression models. For example, we observed high model stability between principal components analysis (PCA), independent components analysis (ICA), and non-negative matrix factorization (NMF). We identified more unique biological signatures in ensembles of denoising autoencoder (DAE) and variational autoencoder (VAE) models in intermediate latent dimensionalities. However, we captured the most pathway-associated features using all compressed features across algorithms and dimensionalities. Optimized at different latent dimensionalities, compression models detect generalizable gene expression signatures representing sex, neuroblastoma MYCN amplification, and cell types. In two supervised machine learning tasks, compressed features optimized predictions at different latent dimensionalities.ConclusionsThere is no single best latent dimensionality or compression algorithm for analyzing gene expression data. Instead, using feature ensembles from different compression models across latent space dimensionalities optimizes biological representations.

Preprints allow researchers to make their findings available to the scientific community before they have undergone peer review. Studies on preprints within bioRxiv have been largely focused on article metadata and how often these preprints are downloaded, cited, published, and discussed online. A missing element that has yet to be examined is the language contained within the bioRxiv preprint repository. We sought to compare and contrast linguistic features within bioRxiv preprints to published biomedical text as a whole as this is an excellent opportunity to examine how peer review changes these documents. The most prevalent features that changed appear to be associated with typesetting and mentions of supplementary sections or additional files. In addition to text comparison, we created document embeddings derived from a preprint-trained word2vec model. We found that these embeddings are able to parse out different scientific approaches and concepts, link unannotated preprint-peer reviewed article pairs, and identify journals that publish linguistically similar papers to a given preprint. We also used these embeddings to examine factors associated with the time elapsed between the posting of a first preprint and the appearance of a peer reviewed publication. We found that preprints with more versions posted and more textual changes took longer to publish. Lastly, we constructed a web application (https://greenelab.github.io/preprint-similarity-search/) that allows users to identify which journals and articles that are most linguistically similar to a bioRxiv or medRxiv preprint as well as observe where the preprint would be positioned within a published article landscape.

The development, production, and distribution of vaccines is imperative to saving lives, preventing illness, and reducing the economic and social burdens caused by the COVID-19 pandemic. Vaccines that use cutting-edge biotechnology have played an important role in mitigating the effects of SARS-CoV-2.

The SARS-CoV-2 pandemic has caused untold damage globally, presenting unusual demands on but also unique opportunities for vaccine development. The development, production, and distribution of vaccines are imperative to saving lives, preventing severe illness, and reducing the economic and social burdens caused by the COVID-19 pandemic.

Preprints allow researchers to make their findings available to the scientific community before they have undergone peer review. Studies on preprints within bioRxiv have been largely focused on article metadata and how often these preprints are downloaded, cited, published, and discussed online. A missing element that has yet to be examined is the language contained within the bioRxiv preprint repository. We sought to compare and contrast linguistic features within bioRxiv preprints to published biomedical text as a whole as this is an excellent opportunity to examine how peer review changes these documents. The most prevalent features that changed appear to be associated with typesetting and mentions of supporting information sections or additional files. In addition to text comparison, we created document embeddings derived from a preprint-trained word2vec model. We found that these embeddings are able to parse out different scientific approaches and concepts, link unannotated preprint–peer-reviewed article pairs, and identify journals that publish linguistically similar papers to a given preprint. We also used these embeddings to examine factors associated with the time elapsed between the posting of a first preprint and the appearance of a peer-reviewed publication. We found that preprints with more versions posted and more textual changes took longer to publish. Lastly, we constructed a web application (https://greenelab.github.io/preprint-similarity-search/) that allows users to identify which journals and articles that are most linguistically similar to a bioRxiv or medRxiv preprint as well as observe where the preprint would be positioned within a published article landscape.

The COVID-19 pandemic catalyzed the rapid dissemination of papers and preprints investigating the disease and its associated virus, SARS-CoV-2. The multifaceted nature of COVID-19 demands a multidisciplinary approach, but the urgency of the crisis combined with the need for social distancing measures present unique challenges to collaborative science. We applied a massive online open publishing approach to this problem using Manubot. Through GitHub, collaborators summarized and critiqued COVID-19 literature, creating a review manuscript. Manubot automatically compiled citation information for referenced preprints, journal publications, websites, and clinical trials. Continuous integration workflows retrieved up-to-date data from online sources nightly, regenerating some of the manuscript's figures and statistics. Manubot rendered the manuscript into PDF, HTML, LaTeX, and DOCX outputs, immediately updating the version available online upon the integration of new content. Through this effort, we organized over 50 scientists from a range of backgrounds who evaluated over 1,500 sources and developed seven literature reviews. While many efforts from the computational community have focused on mining COVID-19 literature, our project illustrates the power of open publishing to organize both technical and non-technical scientists to aggregate and disseminate information in response to an evolving crisis.