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Chapter 4 Conclusions and Future Works

4.2 Major Contributions and Future Works

Here, we have developed an approach to infer protein-protein interactions from domain-domain interactions. The most important contribution of this thesis is the domain-domain interactions we obtained are real interacting domains. It is quiet different to probabilistic domain-domain interaction models. Our domain-domain interactions are more significant and reliable than probabilistic domain-domain interaction models. According to these domain-domain interactions, we predicted 101483 protein pairs on eight common organism models. It is a great quantity more than the data stored in DIP or MIPS database.

Nowadays, we mapped the protein-protein binding site to Pfam domains to identify the domain-domain interactions. However, we considered that the Pfam defined domains are based on HMM-profile and multiple sequence alignment, it might lose structural information.

Our method depends on the domain classification database to infer proteins which were composed of specific domains. The quality of domain classification database will great influence our predictions. In the future, we hope to infer proteins which were composed of specific domains including structural information. We will employ other domain classification systems which include structural information to improve our method.

Our scoring function depends on high quality, curated annotations and sequence similarity. We employed the annotation information in Swiss-prot database and took the

“keywords” to measure the protein function similarity. We only took the “keywords”

information to construct our scoring function. The keywords might be too rough to classify protein functions. We will combine other annotation in Swiss-prot database (e.g. descriptions, functions and EC numbers) to improve our scoring function.

Sometimes, protein-protein interactions might unnecessary belongs to the same organism (e.g. enzyme-inhibitor; virus-host proteins). Our method will ignore these kinds of

protein-protein interactions. We will study the domains which will interact across organisms (e.g. inhibitors and virus proteins). We will modify our approach to recover these kinds of protein-protein interactions.

Another difficulty is that it is often impossible to distinguish between direct physical interactions and functional associations that may not involve direct atomic contacts between macromolecules. According to our approach, we focused on identify structural domain-domain interactions from crystal structures. These kinds of protein-protein interactions are all most the direct physical interactions. Therefore, our method might not be able to predict the transient protein-protein interactions. In the future works, we will identify other more domain-domain interactions from other data source (e.g. DIP and MIPS) to predict transient protein-protein interactions.

Table 1. Protein-protein interactions stored in different database. In total, we inferred 101483 protein-protein interactions on eight common organism models.

Species Our predictions DIP PDB

Homo sapiens 53669 1783 482

Mus musculus 39689 312 326

Rattus norvegicus 4461 129 78

Drosophila melanogaster 857 12019 6

Caenorhabditis elegans 941 3878 1

Saccharomyces cerevisiae 1130 18274 259

Escherichia coli 603 1602 88

Helicobacter pylori 133 134 1

Total 101483 38131 1241

Table 2. 1008 Domain-domain interactions we inferred from structural protein-protein interactions.

PF00001-PF00001; PF00001-PF02978; PF00004-PF00004; PF00004-PF00705; PF00004-PF02617; PF00004-PF07499;

PF00005-PF00005; PF00005-PF01032; PF00006-PF00006; PF00006-PF00231; PF00006-PF00306; PF00006-PF04568;

PF00007-PF00007; PF00007-PF00236; PF00008-PF00008; PF00008-PF00089; PF00009-PF00009; PF00009-PF00889;

PF00009-PF03143; PF00009-PF03764; PF00010-PF01056; PF00011-PF00011; PF00012-PF00012; PF00012-PF01025;

PF00012-PF02179; PF00013-PF00013; PF00014-PF00014; PF00014-PF00051; PF00014-PF00089; PF00014-PF00431;

PF00015-PF00015; PF00016-PF00016; PF00016-PF00101; PF00017-PF00017; PF00017-PF00018; PF00018-PF00018;

PF00018-PF00469; PF00018-PF03114; PF00018-PF05038; PF00019-PF00019; PF00020-PF00020; PF00020-PF00229;

PF00022-PF00022; PF00022-PF00063; PF00022-PF00235; PF00022-PF00626; PF00022-PF03372; PF00022-PF04045;

PF00022-PF04062; PF00022-PF04699; PF00022-PF05856; PF00023-PF00023; PF00023-PF00069; PF00023-PF00554;

PF00023-PF01833; PF00024-PF00024; PF00025-PF00025; PF00025-PF01369; PF00025-PF01465; PF00025-PF05351;

PF00026-PF00026; PF00026-PF06394; PF00026-PF07966; PF00027-PF00027; PF00028-PF00028; PF00028-PF00514;

PF00030-PF00030; PF00032-PF00355; PF00032-PF01333; PF00032-PF02167; PF00032-PF02529; PF00032-PF02939;

PF00033-PF00033; PF00033-PF00355; PF00033-PF02921; PF00034-PF00034; PF00034-PF00124; PF00034-PF00141;

PF00034-PF02167; PF00035-PF00035; PF00036-PF00036; PF00036-PF00063; PF00036-PF00069; PF00036-PF00612;

PF00036-PF00992; PF00036-PF02063; PF00036-PF07679; PF00037-PF02427; PF00038-PF00038; PF00040-PF00040;

PF00041-PF00041; PF00041-PF00103; PF00041-PF00489; PF00041-PF00758; PF00041-PF00812; PF00041-PF03039;

PF00041-PF07686; PF00042-PF00042; PF00043-PF00043; PF00044-PF00044; PF00045-PF00965; PF00047-PF00047;

PF00047-PF00516; PF00047-PF07654; PF00048-PF00048; PF00050-PF00050; PF00050-PF00082; PF00050-PF00089;

PF00051-PF00051; PF00051-PF00079; PF00051-PF00594; PF00051-PF00713; PF00051-PF02821; PF00051-PF03974;

PF00051-PF07648; PF00056-PF02866; PF00057-PF00073; PF00059-PF00059; PF00059-PF00089; PF00059-PF00092;

PF00059-PF00129; PF00059-PF01826; PF00061-PF00061; PF00061-PF00576; PF00062-PF00062; PF00062-PF00969;

PF00062-PF00993; PF00062-PF02709; PF00062-PF07654; PF00062-PF07686; PF00063-PF00063; PF00063-PF02736;

PF00064-PF00064; PF00064-PF07654; PF00064-PF07686; PF00067-PF00067; PF00067-PF00258; PF00068-PF00068;

PF00069-PF00069; PF00069-PF00134; PF00069-PF00254; PF00069-PF00688; PF00069-PF01111; PF00069-PF01214;

PF00069-PF02827; PF00069-PF02984; PF00069-PF03261; PF00069-PF05350; PF00069-PF05706; PF00070-PF00070;

PF00070-PF00085; PF00071-PF00071; PF00071-PF00102; PF00071-PF00169; PF00071-PF00415; PF00071-PF00454;

PF00071-PF00595; PF00071-PF00621; PF00071-PF00786; PF00071-PF00996; PF00071-PF01833; PF00071-PF02115;

PF00071-PF02185; PF00071-PF02196; PF00071-PF03545; PF00071-PF06456; PF00071-PF07487; PF00072-PF00072;

PF00072-PF00158; PF00072-PF01627; PF00072-PF04344; PF00072-PF07194; PF00073-PF00073; PF00073-PF00084;

PF00073-PF02226; PF00073-PF07654; PF00073-PF07686; PF00074-PF00074; PF00074-PF07686; PF00075-PF00075;

PF00076-PF00076; PF00077-PF00077; PF00077-PF00078; PF00077-PF00540; PF00077-PF06815; PF00078-PF00078;

PF00078-PF06815; PF00079-PF00079; PF00079-PF00089; PF00079-PF01033; PF00080-PF00080; PF00081-PF00081;

PF00082-PF00082; PF00082-PF00280; PF00082-PF00720; PF00082-PF01483; PF00082-PF02428; PF00082-PF05922;

PF00084-PF00084; PF00085-PF00085; PF00085-PF00476; PF00085-PF03372; PF00085-PF07686; PF00086-PF00112;

PF00087-PF00087; PF00087-PF00135; PF00087-PF02931; PF00088-PF00088; PF00089-PF00089; PF00089-PF00228;

PF00089-PF00280; PF00089-PF00299; PF00089-PF01403; PF00089-PF01826; PF00089-PF02177; PF00089-PF02821;

PF00089-PF02822; PF00089-PF03974; PF00089-PF05375; PF00089-PF07648; PF00092-PF00092; PF00092-PF03921;

PF00092-PF07654; PF00094-PF07686; PF00101-PF00101; PF00101-PF02788; PF00102-PF00102; PF00104-PF00104;

PF00105-PF00105; PF00106-PF00106; PF00107-PF00107; PF00108-PF00108; PF00109-PF00109; PF00109-PF02801;

PF00111-PF00111; PF00111-PF00175; PF00112-PF00112; PF00113-PF00113; PF00114-PF00114; PF00115-PF00116;

PF00115-PF00510; PF00115-PF02046; PF00115-PF05392; PF00115-PF06481; PF00115-PF07835; PF00116-PF00116;

PF00116-PF00510; PF00116-PF02297; PF00116-PF02936; PF00116-PF05392; PF00116-PF07686; PF00116-PF07835;

PF00117-PF00117; PF00117-PF00425; PF00117-PF00977; PF00118-PF00118; PF00118-PF00166; PF00119-PF00137;

PF00121-PF00121; PF00122-PF00122; PF00124-PF00124; PF00124-PF01405; PF00124-PF02276; PF00124-PF02419;

PF00125-PF00125; PF00127-PF00127; PF00127-PF02975; PF00127-PF06433; PF00128-PF00128; PF00128-PF00138;

PF00128-PF00197; PF00128-PF07686; PF00129-PF00129; PF00129-PF00798; PF00129-PF00906; PF00129-PF01454;

PF00129-PF04253; PF00129-PF07654; PF00129-PF07686; PF00134-PF02234; PF00135-PF00135; PF00136-PF00969;

PF00136-PF00993; PF00136-PF03104; PF00137-PF00137; PF00138-PF00138; PF00138-PF00139; PF00139-PF00139;

PF00141-PF00141; PF00142-PF00142; PF00142-PF00148; PF00143-PF00143; PF00144-PF00144; PF00144-PF07467;

PF00147-PF00147; PF00149-PF00149; PF00150-PF00150; PF00151-PF00151; PF00152-PF00152; PF00155-PF00155;

PF00156-PF00156; PF00157-PF00157; PF00158-PF00158; PF00160-PF00160; PF00160-PF00540; PF00161-PF00161;

PF00161-PF00652; PF00162-PF00162; PF00163-PF03719; PF00164-PF00575; PF00166-PF00166; PF00167-PF00167;

PF00167-PF07679; PF00169-PF00169; PF00169-PF07714; PF00170-PF00170; PF00170-PF01833; PF00171-PF00171;

PF00173-PF00173; PF00175-PF00175; PF00177-PF00380; PF00178-PF00178; PF00179-PF00179; PF00179-PF00632;

PF00179-PF07834; PF00180-PF00180; PF00183-PF00183; PF00183-PF03234; PF00184-PF00184; PF00185-PF00185;

PF00185-PF02729; PF00185-PF02748; PF00186-PF00186; PF00186-PF00303; PF00187-PF00187; PF00190-PF00190;

PF00191-PF00191; PF00194-PF00194; PF00196-PF00196; PF00197-PF00197; PF00198-PF00198; PF00200-PF00200;

PF00202-PF00202; PF00203-PF00416; PF00204-PF00204; PF00205-PF00205; PF00208-PF00208; PF00210-PF00210;

PF00211-PF00211; PF00211-PF00503; PF00215-PF00215; PF00216-PF00216; PF00217-PF00217; PF00218-PF00218;

PF00221-PF00221; PF00223-PF00223; PF00223-PF01241; PF00223-PF02427; PF00223-PF02507; PF00223-PF02531;

PF00223-PF02605; PF00223-PF07465; PF00224-PF00224; PF00225-PF00225; PF00227-PF00227; PF00227-PF02251;

PF00227-PF02252; PF00227-PF07724; PF00229-PF00229; PF00229-PF07654; PF00231-PF00401; PF00231-PF02823;

PF00231-PF04627; PF00232-PF00232; PF00233-PF00233; PF00234-PF00234; PF00235-PF00235; PF00236-PF00236;

PF00238-PF00297; PF00238-PF01246; PF00239-PF00239; PF00240-PF00240; PF00240-PF02809; PF00240-PF02845;

PF00241-PF00241; PF00243-PF00243; PF00244-PF00244; PF00244-PF00583; PF00245-PF00245; PF00246-PF02244;

PF00248-PF00248; PF00248-PF02214; PF00251-PF00251; PF00253-PF00318; PF00253-PF00338; PF00253-PF00417;

PF00254-PF00254; PF00258-PF00258; PF00261-PF00261; PF00264-PF00264; PF00266-PF00266; PF00267-PF00267;

PF00268-PF00268; PF00270-PF00270; PF00273-PF00273; PF00273-PF01468; PF00274-PF00274; PF00275-PF00275;

PF00276-PF00831; PF00276-PF00832; PF00278-PF00278; PF00280-PF00280; PF00282-PF00282; PF00285-PF00285;

PF00288-PF00288; PF00290-PF00290; PF00290-PF00291; PF00291-PF00291; PF00292-PF00292; PF00293-PF00293;

PF00294-PF00294; PF00295-PF00295; PF00296-PF00296; PF00300-PF00300; PF00301-PF00301; PF00302-PF00302;

PF00302-PF02898; PF00303-PF00303; PF00306-PF00306; PF00306-PF04568; PF00307-PF00307; PF00310-PF00310;

PF00311-PF00311; PF00312-PF01250; PF00313-PF00313; PF00314-PF00314; PF00316-PF00316; PF00317-PF00462;

PF00318-PF00318; PF00318-PF00333; PF00318-PF00338; PF00318-PF00410; PF00325-PF00325; PF00326-PF00326;

PF00328-PF00328; PF00330-PF00330; PF00331-PF00331; PF00331-PF00553; PF00331-PF00704; PF00332-PF00332;

PF00334-PF00334; PF00337-PF00337; PF00338-PF07650; PF00339-PF02752; PF00340-PF00340; PF00341-PF00341;

PF00341-PF07654; PF00343-PF00343; PF00345-PF02753; PF00348-PF00348; PF00350-PF00350; PF00352-PF00352;

PF00352-PF02751; PF00352-PF07741; PF00354-PF00354; PF00355-PF07686; PF00359-PF00359; PF00365-PF00365;

PF00365-PF02286; PF00368-PF00368; PF00370-PF00370; PF00373-PF00373; PF00374-PF01058; PF00377-PF07654;

PF00381-PF00381; PF00381-PF00391; PF00381-PF07475; PF00381-PF07686; PF00383-PF00383; PF00386-PF00386;

PF00387-PF00388; PF00390-PF00390; PF00394-PF00394; PF00400-PF00400; PF00400-PF00503; PF00400-PF00631;

PF00400-PF02114; PF00400-PF05856; PF00401-PF04627; PF00403-PF00403; PF00405-PF00405; PF00405-PF00969;

PF00405-PF00993; PF00405-PF04253; PF00405-PF07686; PF00406-PF00406; PF00407-PF00407; PF00407-PF07654;

PF00410-PF00410; PF00410-PF03719; PF00413-PF00413; PF00413-PF00965; PF00415-PF00415; PF00419-PF00419;

PF00419-PF02753; PF00421-PF01737; PF00421-PF02419; PF00421-PF02533; PF00421-PF06514; PF00423-PF00423;

PF00425-PF00425; PF00426-PF00426; PF00431-PF00431; PF00432-PF00432; PF00435-PF00435; PF00436-PF00436;

PF00437-PF00437; PF00438-PF00438; PF00441-PF00441; PF00443-PF00443; PF00445-PF00445; PF00447-PF00447;

PF00448-PF00448; PF00448-PF02881; PF00450-PF00450; PF00457-PF00457; PF00457-PF00704; PF00459-PF00459;

PF00462-PF00462; PF00463-PF00463; PF00464-PF00464; PF00465-PF00465; PF00469-PF00469; PF00475-PF00475;

PF00476-PF00476; PF00476-PF07686; PF00478-PF00478; PF00483-PF00483; PF00484-PF00484; PF00485-PF00485;

PF00489-PF00489; PF00490-PF00490; PF00491-PF00491; PF00497-PF00497; PF00501-PF00501; PF00502-PF00502;

PF00502-PF01383; PF00502-PF02972; PF00503-PF00503; PF00503-PF00615; PF00503-PF04868; PF00504-PF00504;

PF00508-PF00508; PF00508-PF00519; PF00509-PF00509; PF00509-PF00969; PF00509-PF00993; PF00509-PF07654;

PF00509-PF07686; PF00510-PF01215; PF00510-PF02046; PF00510-PF02238; PF00510-PF02297; PF00510-PF07835;

PF00511-PF00511; PF00512-PF00512; PF00514-PF00514; PF00514-PF03066; PF00514-PF06384; PF00515-PF00515;

PF00516-PF00516; PF00516-PF00517; PF00517-PF00517; PF00519-PF00519; PF00520-PF00520; PF00523-PF00523;

PF00529-PF00529; PF00531-PF00531; PF00532-PF00532; PF00533-PF00870; PF00533-PF06632; PF00537-PF00537;

PF00538-PF00538; PF00540-PF00540; PF00540-PF00969; PF00540-PF00993; PF00541-PF00541; PF00541-PF07686;

PF00542-PF00542; PF00543-PF00543; PF00545-PF00545; PF00545-PF01337; PF00548-PF00680; PF00549-PF00549;

PF00551-PF00551; PF00554-PF00554; PF00556-PF00556; PF00557-PF00557; PF00560-PF00560; PF00561-PF00561;

PF00562-PF01193; PF00565-PF00565; PF00568-PF00568; PF00571-PF00571; PF00574-PF00574; PF00576-PF00576;

PF00578-PF00578; PF00579-PF00579; PF00580-PF00580; PF00582-PF00582; PF00583-PF00583; PF00587-PF00587;

PF00587-PF03129; PF00588-PF00588; PF00589-PF00589; PF00591-PF00591; PF00594-PF00594; PF00594-PF00713;

PF00594-PF01108; PF00594-PF03973; PF00595-PF00595; PF00595-PF00667; PF00596-PF00596; PF00599-PF00599;

PF00600-PF00600; PF00601-PF00601; PF00607-PF07686; PF00612-PF01031; PF00615-PF05924; PF00619-PF00619;

PF00620-PF00620; PF00623-PF04539; PF00624-PF00624; PF00626-PF00626; PF00632-PF00632; PF00640-PF00640;

PF00645-PF00645; PF00646-PF00646; PF00646-PF01466; PF00648-PF00648; PF00650-PF00650; PF00650-PF01105;

PF00651-PF00651; PF00653-PF00653; PF00654-PF00654; PF00654-PF07686; PF00656-PF00656; PF00657-PF00657;

PF00659-PF00659; PF00668-PF00668; PF00672-PF01036; PF00673-PF00673; PF00676-PF00676; PF00676-PF02780;

PF00677-PF00677; PF00680-PF00680; PF00680-PF00910; PF00681-PF00681; PF00682-PF02396; PF00685-PF00685;

PF00686-PF00686; PF00686-PF01373; PF00686-PF01833; PF00688-PF00688; PF00688-PF01064; PF00688-PF05806;

PF00689-PF00689; PF00692-PF00692; PF00693-PF00693; PF00696-PF00696; PF00697-PF00697; PF00701-PF00701;

PF00702-PF00702; PF00704-PF00704; PF00705-PF02747; PF00708-PF00708; PF00709-PF00709; PF00710-PF00710;

PF00712-PF00817; PF00714-PF00714; PF00714-PF07140; PF00715-PF00715; PF00716-PF00716; PF00717-PF00717;

PF00718-PF00718; PF00718-PF00761; PF00719-PF00719; PF00722-PF00722; PF00723-PF00723; PF00724-PF00724;

PF00725-PF00725; PF00726-PF07654; PF00728-PF00728; PF00729-PF00729; PF00730-PF00730; PF00731-PF00731;

PF00733-PF00733; PF00737-PF06596; PF00753-PF00753; PF00754-PF07654; PF00756-PF00756; PF00757-PF00757;

PF00757-PF01030; PF00758-PF00758; PF00758-PF07654; PF00758-PF07686; PF00759-PF00759; PF00764-PF00764;

PF00766-PF01012; PF00769-PF00769; PF00770-PF02993; PF00772-PF00772; PF00774-PF00774; PF00775-PF00775;

PF00787-PF00787; PF00790-PF00790; PF00793-PF00793; PF00797-PF00797; PF00808-PF00808; PF00809-PF00809;

PF00816-PF00816; PF00817-PF00817; PF00820-PF07654; PF00825-PF00825; PF00827-PF01248; PF00834-PF00834;

PF00840-PF00840; PF00851-PF01577; PF00853-PF00853; PF00853-PF02312; PF00856-PF00856; PF00857-PF00857;

PF00861-PF01157; PF00869-PF00869; PF00869-PF01004; PF00870-PF00870; PF00871-PF00871; PF00878-PF00878;

PF00879-PF00879; PF00881-PF00881; PF00882-PF00882; PF00882-PF01477; PF00883-PF00883; PF00884-PF00884;

PF00885-PF00885; PF00887-PF00887; PF00889-PF00889; PF00889-PF03143; PF00890-PF00890; PF00896-PF00896;

PF00897-PF00897; PF00897-PF01700; PF00903-PF00903; PF00905-PF00905; PF00906-PF00906; PF00907-PF00907;

PF00908-PF00908; PF00913-PF00913; PF00917-PF00917; PF00918-PF00918; PF00921-PF00921; PF00923-PF00923;

PF00926-PF00926; PF00927-PF00927; PF00928-PF01217; PF00928-PF01602; PF00930-PF00930; PF00930-PF00962;

PF00940-PF00940; PF00941-PF01799; PF00943-PF01563; PF00944-PF00944; PF00957-PF00957; PF00957-PF01742;

PF00957-PF05739; PF00957-PF05835; PF00959-PF00959; PF00960-PF00960; PF00963-PF00963; PF00963-PF02018;

PF00964-PF00964; PF00969-PF00969; PF00969-PF00993; PF00969-PF01669; PF00969-PF02072; PF00969-PF02876;

PF00969-PF07654; PF00969-PF07686; PF00975-PF00975; PF00975-PF05932; PF00977-PF00977; PF00979-PF00979;

PF00979-PF05993; PF00982-PF00982; PF00993-PF00993; PF00993-PF01123; PF00993-PF01669; PF00993-PF02072;

PF00993-PF02876; PF00993-PF07654; PF00993-PF07686; PF00994-PF00994; PF00995-PF00995; PF00995-PF05739;

PF00996-PF01239; PF01003-PF01003; PF01004-PF01004; PF01007-PF01007; PF01008-PF01008; PF01012-PF02771;

PF01014-PF01014; PF01022-PF01022; PF01023-PF01023; PF01025-PF01025; PF01029-PF01029; PF01032-PF01032;

PF01036-PF01036; PF01039-PF01039; PF01041-PF01041; PF01042-PF01042; PF01044-PF01044; PF01047-PF01047;

PF01048-PF01048; PF01051-PF01051; PF01052-PF01052; PF01053-PF01053; PF01057-PF01057; PF01063-PF01063;

PF01068-PF01068; PF01070-PF01070; PF01071-PF01071; PF01074-PF07748; PF01081-PF01081; PF01083-PF01083;

PF01094-PF01094; PF01095-PF01095; PF01096-PF04567; PF01099-PF01099; PF01102-PF01102; PF01105-PF01105;

PF01108-PF01108; PF01108-PF07654; PF01109-PF01109; PF01110-PF01110; PF01111-PF01111; PF01112-PF01112;

PF01115-PF01115; PF01115-PF01267; PF01116-PF01116; PF01117-PF01117; PF01118-PF02774; PF01119-PF01119;

PF01121-PF01121; PF01123-PF01123; PF01123-PF02876; PF01126-PF01126; PF01128-PF01128; PF01129-PF01129;

PF01131-PF01131; PF01135-PF01135; PF01137-PF01137; PF01138-PF01138; PF01140-PF01140; PF01142-PF01142;

PF01144-PF01144; PF01149-PF01149; PF01152-PF01152; PF01154-PF01154; PF01156-PF01156; PF01161-PF01161;

PF01166-PF01166; PF01174-PF01174; PF01175-PF01175; PF01177-PF01177; PF01179-PF01179; PF01180-PF01180;

PF01182-PF01182; PF01187-PF01187; PF01188-PF01188; PF01191-PF04998; PF01192-PF04560; PF01193-PF01193;

PF01193-PF01194; PF01193-PF04983; PF01196-PF01196; PF01202-PF01202; PF01212-PF01212; PF01213-PF01213;

PF01214-PF01214; PF01217-PF01602; PF01218-PF01218; PF01220-PF01220; PF01221-PF01221; PF01223-PF01223;

PF01225-PF01225; PF01227-PF01227; PF01229-PF01229; PF01230-PF01230; PF01233-PF01233; PF01238-PF01238;

PF01239-PF01239; PF01243-PF01243; PF01248-PF01547; PF01255-PF01255; PF01259-PF01259; PF01262-PF01262;

PF01262-PF02233; PF01263-PF01263; PF01264-PF01264; PF01266-PF01266; PF01274-PF01274; PF01278-PF01278;

PF01279-PF01279; PF01289-PF01289; PF01293-PF01293; PF01297-PF01297; PF01303-PF01303; PF01306-PF01306;

PF01314-PF01314; PF01315-PF01315; PF01315-PF02738; PF01316-PF01316; PF01318-PF01318; PF01320-PF01320;

PF01320-PF01844; PF01322-PF01322; PF01323-PF01323; PF01325-PF04023; PF01327-PF01327; PF01329-PF01329;

PF01329-PF04814; PF01330-PF01330; PF01333-PF02529; PF01333-PF03742; PF01333-PF05115; PF01336-PF01336;

PF01337-PF01337; PF01339-PF01339; PF01340-PF01340; PF01341-PF01341; PF01342-PF01342; PF01346-PF01346;

PF01351-PF01351; PF01353-PF01353; PF01355-PF01355; PF01361-PF01361; PF01363-PF01363; PF01367-PF01367;

PF01368-PF01368; PF01369-PF01369; PF01370-PF01370; PF01371-PF01371; PF01373-PF01373; PF01374-PF01374;

PF01375-PF01375; PF01375-PF01376; PF01375-PF06453; PF01376-PF01376; PF01380-PF01380; PF01382-PF01382;

PF01391-PF01391; PF01392-PF01392; PF01393-PF01393; PF01394-PF01394; PF01395-PF01395; PF01401-PF01401;

PF01402-PF01402; PF01403-PF01403; PF01404-PF01404; PF01405-PF02419; PF01406-PF01406; PF01411-PF01411;

PF01419-PF01419; PF01421-PF01421; PF01423-PF01423; PF01425-PF01425; PF01426-PF01426; PF01427-PF01427;

PF01441-PF01441; PF01442-PF01442; PF01447-PF01447; PF01450-PF01450; PF01451-PF01451; PF01452-PF01452;

PF01453-PF01453; PF01458-PF01458; PF01465-PF01465; PF01467-PF01467; PF01470-PF01470; PF01473-PF01473;

PF01477-PF01477; PF01477-PF02740; PF01481-PF01481; PF01483-PF01483; PF01488-PF01488; PF01497-PF01497;

PF01501-PF01501; PF01515-PF01515; PF01517-PF01517; PF01521-PF01521; PF01532-PF01532; PF01536-PF01536;

PF01537-PF01537; PF01539-PF01539; PF01539-PF01542; PF01539-PF01560; PF01542-PF01542; PF01542-PF01543;

PF01543-PF01543; PF01543-PF07654; PF01546-PF01546; PF01546-PF07687; PF01547-PF01547; PF01555-PF01555;

PF01557-PF01557; PF01560-PF01560; PF01564-PF01564; PF01568-PF03892; PF01568-PF05738; PF01569-PF01569;

PF01577-PF01577; PF01582-PF01582; PF01583-PF01583; PF01590-PF01590; PF01591-PF01591; PF01593-PF01593;

PF01597-PF01597; PF01601-PF01601; PF01608-PF01608; PF01611-PF01611; PF01613-PF01613; PF01614-PF01614;

PF01625-PF01625; PF01627-PF01627; PF01633-PF01633; PF01634-PF01634; PF01636-PF01636; PF01637-PF01637;

PF01641-PF01641; PF01642-PF01642; PF01652-PF01652; PF01652-PF05456; PF01653-PF01653; PF01658-PF01658;

PF01663-PF01663; PF01664-PF01664; PF01665-PF01665; PF01670-PF01670; PF01700-PF01700; PF01702-PF01702;

PF01704-PF01704; PF01706-PF01706; PF01712-PF01712; PF01725-PF01725; PF01729-PF01729; PF01729-PF02749;

PF01740-PF01740; PF01740-PF02518; PF01741-PF01741; PF01742-PF01742; PF01747-PF01747; PF01750-PF01750;

PF01751-PF01751; PF01756-PF01756; PF01761-PF01761; PF01764-PF01764; PF01780-PF03947; PF01784-PF01784;

PF01791-PF01791; PF01799-PF03450; PF01804-PF01804; PF01807-PF01807; PF01812-PF01812; PF01814-PF01814;

PF01815-PF01815; PF01817-PF01817; PF01818-PF01818; PF01819-PF01819; PF01829-PF01829; PF01833-PF01833;

PF01835-PF01835; PF01842-PF01842; PF01844-PF01844; PF01845-PF01845; PF01857-PF01858; PF01858-PF01858;

PF01862-PF01862; PF01869-PF01869; PF01870-PF01870; PF01880-PF01880; PF01884-PF01884; PF01892-PF01892;

PF01896-PF01896; PF01910-PF01910; PF01920-PF02996; PF01921-PF01921; PF01948-PF01948; PF01965-PF01965;

PF01974-PF01974; PF01978-PF01978; PF01979-PF01979; PF01992-PF01992; PF01993-PF01993; PF01997-PF01997;

PF02011-PF02011; PF02017-PF02017; PF02018-PF02018; PF02025-PF02025; PF02035-PF02035; PF02041-PF02041;

PF02056-PF02056; PF02074-PF02074; PF02075-PF02075; PF02080-PF02080; PF02081-PF02081; PF02085-PF02085;

PF02091-PF02091; PF02098-PF02098; PF02110-PF02110; PF02115-PF02115; PF02121-PF02121; PF02126-PF02126;

PF02129-PF02129; PF02136-PF02136; PF02138-PF02138; PF02142-PF02142; PF02146-PF02146; PF02151-PF02151;

PF02152-PF02152; PF02156-PF02156; PF02157-PF02157; PF02159-PF02159; PF02167-PF02167; PF02167-PF02320;

PF02167-PF05365; PF02172-PF02173; PF02181-PF02181; PF02189-PF07654; PF02197-PF02197; PF02198-PF02198;

PF02210-PF02210; PF02211-PF02211; PF02211-PF02979; PF02214-PF02214; PF02216-PF02216; PF02219-PF02219;

PF02221-PF02221; PF02223-PF02223; PF02226-PF02226; PF02230-PF02230; PF02231-PF02811; PF02233-PF02233;

PF02239-PF02239; PF02240-PF02249; PF02240-PF02745; PF02241-PF02241; PF02241-PF02249; PF02244-PF02244;

PF02249-PF02249; PF02250-PF02250; PF02251-PF02251; PF02251-PF02252; PF02252-PF02252; PF02253-PF02253;

PF02254-PF02254; PF02254-PF07885; PF02255-PF02255; PF02258-PF02258; PF02261-PF02261; PF02264-PF02264;

PF02267-PF02267; PF02270-PF02270; PF02270-PF05793; PF02271-PF02939; PF02273-PF02273; PF02274-PF02274;

PF02275-PF02275; PF02282-PF02282; PF02283-PF02283; PF02284-PF02790; PF02284-PF02936; PF02284-PF02937;

PF02285-PF02935; PF02285-PF02936; PF02286-PF02286; PF02291-PF02969; PF02297-PF02297; PF02298-PF02298;

PF02300-PF02313; PF02301-PF05557; PF02303-PF02303; PF02304-PF02305; PF02305-PF02925; PF02305-PF04726;

PF02306-PF02925; PF02310-PF06368; PF02313-PF02313; PF02319-PF02319; PF02321-PF02321; PF02329-PF02329;

PF02331-PF02331; PF02332-PF02332; PF02334-PF02334; PF02335-PF02335; PF02348-PF02348; PF02350-PF02350;

PF02353-PF02353; PF02359-PF02933; PF02365-PF02365; PF02378-PF02378; PF02391-PF02391; PF02396-PF07836;

PF02404-PF02404; PF02419-PF05151; PF02423-PF02423; PF02427-PF02507; PF02428-PF02428; PF02429-PF02429;

PF02431-PF02431; PF02437-PF02437; PF02441-PF02441; PF02452-PF02452; PF02463-PF02463; PF02502-PF02502;

PF02504-PF02504; PF02511-PF02511; PF02518-PF02518; PF02525-PF02525; PF02529-PF03742; PF02531-PF02605;

PF02542-PF02542; PF02545-PF02545; PF02548-PF02548; PF02556-PF02556; PF02556-PF07517; PF02560-PF02560;

PF02561-PF02561; PF02566-PF02566; PF02567-PF02567; PF02569-PF02569; PF02570-PF02570; PF02574-PF02574;

PF02575-PF02575; PF02577-PF02577; PF02578-PF02578; PF02580-PF02580; PF02581-PF02581; PF02585-PF02585;

PF02590-PF02590; PF02595-PF02595; PF02597-PF05237; PF02602-PF02602; PF02614-PF02614; PF02615-PF02615;

PF02617-PF02861; PF02627-PF02627; PF02657-PF02657; PF02664-PF02664; PF02668-PF02668; PF02670-PF02670;

PF02676-PF02676; PF02700-PF02700; PF02709-PF02709; PF02710-PF02710; PF02710-PF03996; PF02716-PF02716;

PF02730-PF02730; PF02734-PF02734; PF02737-PF02737; PF02738-PF02738; PF02738-PF03450; PF02741-PF02741;

PF02742-PF02742; PF02744-PF02744; PF02746-PF02746; PF02747-PF02747; PF02750-PF02750; PF02751-PF03153;

PF02742-PF02742; PF02744-PF02744; PF02746-PF02746; PF02747-PF02747; PF02750-PF02750; PF02751-PF03153;

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