***TASK***
the task is to simplify the input abstract of a biomedical literature

***INPUT***
the input is the abstract of a biomedical literature

***OUTPUT***
the output is the simplified abstract for the input abstract of a biomedical literature
***DOCUMENTATION*** 
***EXAMPLES*** 
Input:
Output:

***EXAMPLES***
Input: Functionally analogous enzymes are those that catalyze similar reactions on similar substrates but do not share common ancestry, providing a window on the different structural strategies nature has used to evolve required catalysts. Identification and use of this information to improve reaction classification and computational annotation of enzymes newly discovered in the genome projects would benefit from systematic determination of reaction similarities. Here, we quantified similarity in bond changes for overall reactions and catalytic mechanisms for 95 pairs of functionally analogous enzymes (non-homologous enzymes with identical first three numbers of their EC codes) from the MACiE database. Similarity of overall reactions was computed by comparing the sets of bond changes in the transformations from substrates to products. For similarity of mechanisms, sets of bond changes occurring in each mechanistic step were compared; these similarities were then used to guide global and local alignments of mechanistic steps. Using this metric, only 44% of pairs of functionally analogous enzymes in the dataset had significantly similar overall reactions. For these enzymes, convergence to the same mechanism occurred in 33% of cases, with most pairs having at least one identical mechanistic step. Using our metric, overall reaction similarity serves as an upper bound for mechanistic similarity in functional analogs. For example, the four carbon-oxygen lyases acting on phosphates (EC 4.2.3) show neither significant overall reaction similarity nor significant mechanistic similarity. By contrast, the three carboxylic-ester hydrolases (EC 3.1.1) catalyze overall reactions with identical bond changes and have converged to almost identical mechanisms. The large proportion of enzyme pairs that do not show significant overall reaction similarity (56%) suggests that at least for the functionally analogous enzymes studied here, more stringent criteria could be used to refine definitions of EC sub-subclasses for improved discrimination in their classification of enzyme reactions. The results also indicate that mechanistic convergence of reaction steps is widespread, suggesting that quantitative measurement of mechanistic similarity can inform approaches for functional annotation.
Output:  When species evolve, their genes duplicate and diverge to allow for adaptation of their functional repertoires to the changing environment. In this scenario, unrelated genes can convergently evolve to produce proteins with the same molecular function, termed “functionally analogous.” A quantitative determination of the reaction similarities among functionally analogous enzymes could provide insight about the different structural solutions nature has used to evolve similar catalysts. Bond changes between substrates and products, and between successive reaction intermediates, were used to compare the reactions catalyzed and the mechanisms of catalysis for 95 pairs of functionally analogous enzymes. Less than half of the reactions catalyzed by unrelated enzymes, but defined as similar by the Enzyme Commission (EC) classification, are similar in terms of bond changes, suggesting that this classification often fails to capture quantitative differences between many enzyme reactions. Furthermore, we addressed for the first time whether the chemical mechanisms by which similar overall reactions are achieved in functional analogs are also similar. We conclude that convergence of reaction is often accompanied by convergence of chemical mechanism. These results will be useful for classifying enzymes, guiding functional annotation of newly determined enzyme sequences and structures and for informing the engineering of enzymes with new functions.

Input:  Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological
                    malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A
                    previous genome-wide association study has established a marker, rs10484561 in
                    the human leukocyte antigen (HLA) class II region on 6p21.32 associated with
                    increased FL risk. Here, in a three-stage genome-wide association study,
                    starting with a genome-wide scan of 379 FL cases and 791 controls followed by
                    validation in 1,049 cases and 5,790 controls, we identified a second independent
                    FL–associated locus on 6p21.32, rs2647012
                    (ORcombined = 0.64,
                        Pcombined = 2×10−21)
                    located 962 bp away from rs10484561 (r2<0.1 in controls). After
                    mutual adjustment, the associations at the two SNPs remained genome-wide
                    significant (rs2647012:ORadjusted = 0.70,
                        Padjusted = 4×10−12;
                        rs10484561:ORadjusted = 1.64,
                        Padjusted = 5×10−15).
                    Haplotype and coalescence analyses indicated that rs2647012 arose on an
                    evolutionarily distinct haplotype from that of rs10484561 and tags a novel
                    allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up
                    analysis of the top 6 FL–associated SNPs in 4,449 cases of other NHL
                    subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma
                        (ORcombined = 1.36,
                        Pcombined = 1.4×10−7).
                    Our results reveal the presence of allelic heterogeneity within the HLA class II
                    region influencing FL susceptibility and indicate a possible shared genetic
                    etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA
                    class II region plays a complex yet important role in NHL.


Output:

Earlier studies have established a marker rs10484561, in the HLA class II region
                    on 6p21.32, associated with increased follicular lymphoma (FL) risk. Here, in a
                    three-stage genome-wide association study of 1,428 FL cases and 6,581 controls,
                    we identified a second independent FL–associated marker on 6p21.32,
                    rs2647012, located 962 bp away from rs10484561. The associations at two SNPs
                    remained genome-wide significant after mutual adjustment. Haplotype and
                    coalescence analyses indicated that rs2647012 arose on an evolutionarily
                    distinct lineage from that of rs10484561 and tags a novel allele with an
                    opposite, protective effect on FL risk. Moreover, in an analysis of the top 6
                    FL–associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was
                    associated with risk of diffuse large B-cell lymphoma. Our results reveal the
                    presence of allelic heterogeneity at 6p21.32 in FL risk and suggest a shared
                    genetic etiology with the common diffuse large B-cell lymphoma subtype.
