Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Characterization of Mammalian ADAM2 and Its Absence from Human Sperm.

The members of the ADAM (a disintegrin and metalloprotease) family are membrane-anchored multi-domain proteins that play prominent roles in male reproduction. ADAM2, which was one of the first identified ADAMs, is the best studied ADAM in reproduction. In the male germ cells of mice, ADAM2 and other ADAMs form complexes that contribute to sperm-sperm adhesion, sperm-egg interactions, and the migration of sperm in the female reproductive tract. Here, we generated specific antibodies against mouse and human ADAM2, and investigated various features of ADAM2 in mice, monkeys and humans. We found that the cytoplasmic domain of ADAM2 might enable the differential association of this protein with other ADAMs in mice. Western blot analysis with the anti-human ADAM2 antibodies showed that ADAM2 is present in the testis and sperm of monkeys. Monkey ADAM2 was found to associate with chaperone proteins in testis. In humans, we identified ADAM2 as a 100-kDa protein in the testis, but failed to detect it in sperm. This is surprising given the results in mice and monkeys, but it is consistent with the failure of ADAM2 identification in the previous proteomic analyses of human sperm. These findings suggest that the reproductive functions of ADAM2 differ between humans and mice. Our protein analysis showed the presence of potential ADAM2 complexes involving yet-unknown proteins in human testis. Taken together, our results provide new information regarding the characteristics of ADAM2 in mammalian species, including humans

Biochemical characteristics of ADAM2 in monkey and human sperm.

<p><b>A</b> and <b>C.</b> Monkey sperm were boiled in 3% SDS with (lane 1) or without (lanes 2 and 3) 5% β-mercaptoethanol, resolved by SDS-PAGE and blotted with <b>A</b>. anti-hADAM2-Cys and <b>C</b>. anti-hADAM2-CyT. The 47-kDa band in the β-mercaptoethanol-free sample was exposed to mercaptoethanol diffusing from the adjacent lane (left). Thus, it is mostly reduced on the left side of the lane and mostly non-reduced on the right side of the lane. <b>B</b> and <b>D</b>. Human sperm were boiled in 3% SDS with (lane 1) or without (lanes 2 and 3) 5% β-mercaptoethanol, resolved by SDS-PAGE and blotted with <b>B.</b> anti-hADAM2-Cys and <b>D</b>. anti-hADAM2-CyT. Experiments were repeated twice. Reduced and non-reduced samples were subjected to SDS-PAGE using 10% resolving gels. Abbreviation: β-ME, β-mercaptoethanol. Molecular masses are presented on the left.</p

Immunoreactivity of mouse ADAM2 antibodies.

<p>Lysates from testicular cells and sperm from wild-type and <i>Adam2</i>^<i>-/-</i> mice were boiled in 3% SDS and 5% β-mercaptoethanol and subjected to Western blot analyses. <b>A</b>. Western blotting with the anti-mADAM2-D antibody. This antibody was raised against the ADAM2 disintegrin domain, and recognized the precursor (100-kDa) and processed (45-kDa) forms of ADAM2 in mouse testis and sperm, respectively. <b>B</b> and <b>C</b>. Blots performed using two different antibodies, which were raised against the cytoplasmic tail domain and designated <b>B</b>. anti-mADAM2-CyT-1 and <b>C</b>. anti-mADAM2-CyT-2. <b>D</b>. An antibody against a-tubulin (TUBA) was included as a control. Experiments were repeated three times. Reduced protein samples were subjected to SDS-PAGE using 10% resolving gels. Abbreviations: T, testicular cells; S, sperm; WT, wild-type; A2^-/-, <i>Adam2</i>^<i>-/-</i>; NS, non-specific. Molecular masses are presented on the left.</p

Possible ADAM2 complexes in monkey and human testicular cells.

<p><b>A</b> and <b>C.</b> The non-reduced supernatants from the lysates of monkey testis were either boiled in 3% SDS (lane 2) or incubated at room temperature in 0.3% SDS (lane 1), and then immunoblotted with <b>A.</b> anti-hADAM2-Cys and <b>C.</b> anti-hADAM2-CyT. <b>B</b> and <b>D.</b> A similar experiment was performed using extracts from human testis immunoblotted with <b>B.</b> anti-hADAM2-Cys and <b>D.</b> anti-hADAM2-CyT. Asterisks and arrowheads indicate the ADAM2 complexes and monomers, respectively. Experiments were repeated three times. Reduced and non-reduced potein samples were subjected to SDS-PAGE using 8% resolving gels. Abbreviation: β-ME, β-mercaptoethanol. Molecular masses are presented on the left.</p

Previous proteomic analyses.

<p>Previous proteomic analyses.</p

Immunoprecipitation with anti-hADAM2-CyT.

<p>Immunoprecipitation of ADAM2 was carried out using monkey testis lysates. Immunoprecipitation using normal rabbit serum was performed as a negative control. Immunoprecipitated lysates were immunoblotted with anti-hADAM2-CyT. Experiments were repeated three times. Reduced protein samples were subjected to SDS-PAGE using 8% resolving gel. Abbreviations: TL, tissue lysate (100 μg); S, supernatant; and IP, immunoprecipitated protein (1 mg); and NRS, normal rabbit serum.</p

Coimmunoprecipitation of ADAM2 in mouse testes.

<p><b>A</b> and <b>B</b>. Testes from wild-type and <i>Adam2</i>^<i>-/-</i> mice were lysed with 1% NP-40 buffer, the tissue lysates were immunoprecipitated with <b>A</b>. anti-mADAM2-CyT-1 and <b>B</b>. anti-mADAM2-CyT-2, and the resolved immunoprecipitates were immunoblotted with anti-mADAM2-D. Normal rabbit serum was used as a control. <b>C</b> and <b>D</b>. Lysates were precipitated with <b>C</b>. anti-mADAM2-Cyt-1 and <b>D</b>. anti-mADAM2-CyT-2 and analyzed by immunoblotting with anti-mADAM2-D, anti-mADAM1B, and anti-mADAM3. Experiments were repeated five times. Reduced protein samples were subjected to SDS-PAGE using 8% resolving gels. Abbreviations: WT, wild-type; A2^<i>-/-</i>, <i>Adam2</i>^<i>-/</i>; TL, tissue lysate (100 μg); IP, immunoprecipitated protein (1 mg); NRS, normal rabbit serum; and IB, immunoblotting.</p