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Central to the U.S. precision medicine initiative is the notion that Big Data, properly collected and analyzed, will reveal subtypes of diseases we currently view as single disorders. But what about small data sets? Is there translational value to meta-analyses of existing or newly generated data sets that aren’t part of large studies? Now, Planey and Gevaert bring together small data sets and show that the answer is yes. The investigators aim was to identify subtypes of disease, but many of the studies they used were too small to reveal robust subtypes on their own. So they developed a computational meta-analysis procedure called CoINcIDE—which used clustering to identify disease subtypes within each individual data set—and found cross–data set clusters of similar subtypes. Performing clustering within studies followed by cross-study comparison sidesteps obstacles such as platform or study effects that could hinder subtype discovery. Cross–data set analysis with CoINcIDE identified robust disease subtypes in both simulated and patient biopsy data from studies of breast and ovarian cancer. The authors performed the analysis of ovarian cancers both with and without the largest data set, TCGA. With 578 ovarian cancers, TCGA was more than twice as large as any other data set. Results were consistent whether or not TCGA was included, highlighting the power of smaller data sets paired with the CoINcIDE method for subtype discovery. The CoINcIDE analyses add to the literature on ovarian-cancer subtypes associated with survival; however, work to confirm the predictive nature of these subtypes or to identify effective subtype-specific treatments remains to be done. As a next step, the biological basis of the gene expression signals that give rise to the CoINcIDE subtypes needs to be identified, and the underlying mechanisms should be determined. Vincent van Gogh wrote, “Great things are not done by impulse, but by a series of small things brought together.” CoINcIDE might empower researchers to perform subtype-discovery for rare diseases, which otherwise would be impossible for a single lab or initiative because of the small numbers of samples. By developing a computational method that brings together small data sets, the authors transform the vast array of disease-relevant, publicly available data into opportunities for subtype discovery. C. R. Planey, O. Gevaert, CoINcIDE: A framework for discovery of patient subtypes across multiple data sets. Genome Med . 10.1186/s13073-016-0281-4 (2016). [[Full Text]][1] [1]: https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-016-0281-4

Congress this week began voting on a sweeping biomedical innovation bill that includes nearly $5 billion in dedicated funding for a trio of major research initiatives at the National Institutes of Health (NIH). The bill also includes measures to speed the approval of new drugs and medical devices by the Food and Drug Administration, and it would create a mechanism for catalyzing efforts to streamline federal regulations that universities and academic researchers regard as burdensome. The bipartisan bill, known as the 21st Century Cures Act, is the culmination of more than 2 years of lobbying by research, patient, and industry groups, and extensive negotiations between members of the Senate and the House of Representatives. The bill includes a long list of largely uncontroversial NIH provisions, including calls for the agency to produce a comprehensive strategic plan, set up a special initiative for young scientists, establish a prize to incentivize certain kinds of research, and take new steps to encourage data sharing and ensure the reproducibility of NIH-funded research. And research lobbyists are delighted with provisions that set aside $4.8 billion over the next 10 years for three NIH initiatives: $1.4 billion for Obama's Precision Medicine Initiative, $1.8 billion for Vice President Joe Biden's cancer moonshot, and $1.6 billion for the White House's Brain Research through Advancing Innovative Neurotechnologies Initiative. The bill also provides $30 million over 3 years for regenerative medicine research using adult stem cells. But biomedical research advocates are worried how the funding may ultimately play out, and other bureaucratic provisions they say could be burdensome.

Next year, the National Institutes of Health (NIH) expects to begin recruiting at least 1 million people for what may become the world's largest study of how genes influence disease risks and drug responses. Plans for the study came into focus last week with the release of a blueprint from a panel of human geneticists, medical researchers, and other experts. It urged that NIH recruit participants not only through academic medical centers and health care organizations, but also by issuing an open invitation to anyone living in the United States. For NIH Director Francis Collins, the project, known as the Precision Medicine Initiative (PMI) Cohort Program, brings to fruition an idea he first proposed 11 years ago. But whether NIH can design and effectively manage such a massive endeavor remains an open question.

By all accounts, President Obama's Precision Medicine Initiative (PMI) promising molecular-guided diagnostics, therapeutics, and prevention strategies is eliciting enthusiasm and excitement among clinicians, translational researchers, and patients (“NIH plots million-person megastudy,” J. Kaiser

Reading the Perspective “Combating emerging viral threats” by E. Bekerman and S. Einav (17 April, p. [282][1]), I was struck by the call for broad-spectrum antiviral drugs, given the recognition of the problems caused by broad-spectrum antibacterial drugs ([ 1 ][2]) and the recent clarion calls for precision medicine ([ 2 ][3]). “One drug, one bug” antibiotics, along with appropriate point-of-intervention diagnostics, would mitigate the spread of drug resistance. The same is likely to be true for antivirals. Furthermore, “one drug, multiple bugs” (broad-spectrum) antibiotics damage the highly diverse populations of bacteria in and on our body. These microbiota are becoming increasingly appreciated as critical for health. Damage to the gut microbiota, particularly during early development, has lasting negative consequences for maturation and function of the immune and central nervous systems ([ 3 ][4]). The gut microbiota similarly harbor viral components important for health ([ 4 ][5]). Broad-spectrum antivirals are likely to damage these viral components of our gut microbiota. ![Figure][6] IMAGE: © ROEL SMART/[ISTOCKPHOTO.COM][7] Today's slow and expensive drug development process pressures industry to seek one drug for multiple bugs. However, efforts to manage viral infections, as for bacterial infections, should not focus on broad-spectrum agents but on technology platforms that allow the discovery, development, manufacturing, and regulatory approval of multiple precision antiviral agents, each targeting only one bug. Such drugs could be developed, produced, and approved expeditiously and cost-effectively, as the world has managed to achieve effectively for annual influenza vaccines in most years. 1. [↵][8]Center for Disease Control and Prevention, “Antibiotic resistance threats in the United States, 2013” (2013); [www.cdc.gov/drugresistance/threat-report-2013/][9]. 2. [↵][10]The White House, Fact Sheet: President Obama's Precision Medicine Initiative ([www.whitehouse.gov/the-press-office/2015/01/30/fact-sheet-presidentobama-s-precision-medicine-initiative][11]). 3. [↵][12]1. M. J. Blaser , Missing Microbes (Henry Holt and Company, New York, 2014). 4. [↵][13]1. H. W. Virgin , Cell 157, 142 (2014). [OpenUrl][14][CrossRef][15][PubMed][16][Web of Science][17] [1]: /lookup/doi/10.1126/science.aaa3778 [2]: #ref-1 [3]: #ref-2 [4]: #ref-3 [5]: #ref-4 [6]: pending:yes [7]: http://ISTOCKPHOTO.COM [8]: #xref-ref-1-1 "View reference 1 in text" [9]: http://www.cdc.gov/drugresistance/threat-report-2013/ [10]: #xref-ref-2-1 "View reference 2 in text" [11]: http://www.whitehouse.gov/the-press-office/2015/01/30/fact-sheet-presidentobama-s-precision-medicine-initiative [12]: #xref-ref-3-1 "View reference 3 in text" [13]: #xref-ref-4-1 "View reference 4 in text" [14]: {openurl}?query=rft.jtitle%253DCell%26rft.volume%253D157%26rft.spage%253D142%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.cell.2014.02.032%26rft_id%253Dinfo%253Apmid%252F24679532%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [15]: /lookup/external-ref?access_num=10.1016/j.cell.2014.02.032&link_type=DOI [16]: /lookup/external-ref?access_num=24679532&link_type=MED&atom=%2Fsci%2F348%2F6242%2F1437.1.atom [17]: /lookup/external-ref?access_num=000333968900013&link_type=ISI

Days before the release of the overall federal budget request, the White House began talking up two new flagship scientific efforts. The $215 million Precision Medicine Initiative, first mentioned in President Barack Obama9s 20 January State of the Union address, aims to advance personalized medicine in part by assembling a database containing genetic and medical information from at least 1 million Americans. The other is a roughly $1.2 billion multiagency effort to combat the mounting public health crisis of antibiotic-resistant infections. The National Institutes of Health, which would receive an overall 3.3% increase to $31.3 billion, would play a key role in both campaigns. The two initiatives have drawn encouraging words from members of Congress in both parties.